Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Human Flora, Intestinal Dysbiosis and the Neuro-Endo-Immune Connection by Mark J Donohue Introduction Did you know…? The human “gut” is synonymous with the human “intestine”. In a healthy human, the internal tissues - blood, brain, muscle, etc. - are normally free of microorganisms or microbes (unicellular organisms). However, the surface tissues - skin and mucous membranes - are constantly in contact with environmental organisms and become readily colonized by various microbial species which are referred to as normal human flora. The normal flora of humans consists of a few fungi and protists (parasites, amoebas, etc.), but bacteria are the most numerous and obvious microbial components. While most of the activities of the normal flora benefit their host, some of the normal flora are parasitic (live at the expense of their host), and some are pathogenic (capable of producing disease). Diseases that are produced by the normal flora in their host may be called endogenous diseases (originating from inside the body). Most endogenous bacterial diseases are opportunistic infections, meaning that the organism must be given a special opportunity of weakness in the host defenses in order to infect. Sometimes the relationship between a member of the normal flora and its host cannot be deciphered. Such a relationship where there is no apparent benefit or harm to either organism during their association is referred to as a commensal relationship. Many of the normal flora that are not predominant in their habitat, even though always present in low numbers, are thought of as commensal bacteria. Most members of the normal flora prefer to colonize certain tissues and not others. This tissue specificity is usually due to properties of both the host and the microorganism. A human first becomes colonized by normal flora at the moment of birth and passage through the birth canal. In utero, the fetus is sterile, but when the mother's water breaks and the birth process begins, so does colonization of the body surfaces. Handling and feeding of the infant after birth leads to establishment of a stable normal flora on the skin, oral cavity and intestinal tract in about 48 hours. Microorganisms/Microbes As mentioned the normal human flora consist of fungi, protists (parasites, amoebas, etc.) and bacteria Fungi: Fungi (plural) or fungus (singular) are small, often microscopic, plant-like organisms. Fungi include microorganisms such as yeast and molds, as well as the more familiar mushrooms. Fungi lack chlorophyll and vascular tissue. However, unlike bacteria fungi do contain a membrane-bound nucleus and other membrane-bound organelles like mitochondria. Fungi range in form from a single cell to a body mass of branched filamentous hypae (cylindrical, thread-like structures) that often produce specialized fruiting bodies. Fungi feed on organic matter. Life Domain Kingdom Phylum Protists: A protists is any organism that is not a plant, animal or fungus. Parasites, protozoa, amoeba and algae are the more common protists. Although there is a lot of variety within protists, they do share some common characteristics: All protists are eukaryotic (cells with nuclei). All protists live in moist environments. Protists can be unicellular or multicellular. Protists can be microscopic or can be over 300 feet long. Class Order Family Genus Species Strain Microorganism classifications Bacteria: Bacteria are microscopic organisms whose single cells have neither a membrane-bounded nucleus nor other membrane-bounded organelles like mitochondria and chloroplasts. Bacteria are classified according to their: Shape – bacilli (rod-shaped), cocci (spherical), spirilla (curved walls). Ability to form spores. Method of energy production – anaerobic (not requiring oxygen), or aerobic (requires oxygen). Reaction to Gram stain – Gram-positive (stained violet), Gram-negative (won’t stain violet but will stain pink). Normal Flora in Humans Current research has indicated that there are thousands of species of normal flora in humans. Collectively, the genetic makeup of normal human flora is referred to as the human microbiome. And just as scientist deciphered the human genome, the NIH (National Institutes of Health) is now in involved in a major project to decipher the human microbiome. Obviously, it is beyond the scope of this report to list what species are known to be a part of normal human flora. Instead below is a list of the more common species and their tissue specificity. NOTE (**) denotes a possible pathogenic microbe. Skin The skin contains – thousands of microbes per cm (0.4 inch) of tissue. The adult human is covered with approximately 2 square meters of skin. The density and composition of the normal flora of the skin varies with anatomical locale. The high moisture content of the axilla (arm pits), groin, and areas between the toes supports the activity and growth of relatively high densities of microbes, but the density of microbe populations at most other sites is fairly low. Common microbes found on the skin are: Corynebacteria species o C. parvum (propionibacterium acnes) – cause acne when trapped in a hair follicle. Also produces fatty acids that inhibit the growth of fungi and yeast on the skin. Micrococcus species o M. luteus – transforms compounds in sweat into compounds with an unpleasant odor. Staphylococcus species o S. epidermidis – is highly adapted to the diverse environments of its human host. Also produces fatty acids that inhibit the growth of fungi and yeast on the skin. o S. aureus ** – is a potential pathogen. It is a leading cause of bacterial disease in humans. It can cause a range of illnesses from minor skin infections and abscesses to life threatening diseases such as pneumonia and meningitis. S. aureus is found on the face and hands in individuals who are nasal carriers. This is because the face and hands are likely to become inoculated with the bacteria from the nasal membranes. Such individuals may auto-inoculate themselves with the pathogen or spread it to other individuals or foods. Eye (conjunctiva) The conjunctiva is kept moist and healthy by the continuous secretions from the lachrymal glands. Lachrymal secretions (tears) also contain bactericidal (kills bacteria) substances including lysozyme. Blinking wipes the conjunctiva every few seconds mechanically washing away foreign objects including bacteria. There is little or no opportunity for microorganisms to colonize the conjunctiva without special mechanisms to attach to the epithelial surfaces and some ability to withstand attack by lysozyme. With that said a variety of microbes may be cultivated from the normal conjunctiva, but the number of organisms is usually small. The dominant microbes in the eye are the same as those found on the skin - Staphylococcus epidermidis and Corynebacteria parvum. Upper Respiratory Tract The upper respiratory tract (nose, nasopharynx, pharynx) are heavily colonized with a large number of microbes. The healthy sinuses, in contrast, are sterile. The most common microbes found in the upper respiratory tract are again Staphylococcus epidermidis and Corynebacteria parvum. However, sometimes found in the upper respiratory tract are pathogenic microbes such as: Corynebacteria diphtheria** - causes diphtheria an upper respiratory tract illness. Haemophilus influenza** - is a frequent secondary invader to viral influenza. Neisseria meningitides** - are frequent inhabitants of the upper respiratory tract, mainly the pharynx and is an important cause of bacterial meningitis. Staphylococcus aureus** - is the leading cause of staph infections. Streptococcus pneumonia** - is present in the upper respiratory tract of about half the population. If it invades the lower respiratory tract it can cause pneumonia. S.pneumoniae causes 95 percent of all bacterial pneumonia. Streptococcus pyogenes** - causes tonsillitis, strep throat, pneumonia, endocarditis (inflammation of heart). Some streptococcal diseases can lead to rheumatic fever or nephritis which can damage the kidneys. The Lower Respiratory Tract The lower respiratory tract (trachea, bronchi and pulmonary tissue) is virtually free of microorganisms, mainly because of the efficient cleansing action of the ciliated epithelium which lines the tract. Any bacteria reaching the lower respiratory tract are swept upward by the action of the mucociliary blanket that lines the bronchi. They are subsequently removed by coughing, sneezing, and swallowing. However, if the respiratory tract epithelium becomes damaged, as in bronchitis or viral pneumonia, the individual may become susceptible to infection by pathogens such as H. influenzae or S. pneumoniae descending from the nasopharynx (upper respiratory tract). The Urogenital Tract The urethra (tube connecting to bladder for urine elimination) contains – less than 100 microbes per cm (0.4 inch) of tissue. The bladder and kidneys are sterile and have none. Urine is normally sterile, and since the urinary tract is flushed with urine every few hours, microorganisms have problems gaining access and becoming established. The flora of the anterior urethra, as indicated principally by urine cultures, suggests that the area may be inhabited by a relatively consistent normal flora consisting of Staphylococcus epidermidis, and Enterococcus faecalis**. Enterococcus faecalis are normally commensal, but can become opportunistic and cause infections in the bladder, epididymis (testicle), and prostate. Reproductive Tract The vagina contains – thousands of microbes per cm (0.4 inch) of tissue. The urethra and prostate contains – less than 100 microbes per cm of tissue. The predominate microbe in the vagina is: – Lactobacillus acidophilus – The vaginal epithelium contains glycogen (polysaccharide similar to starch) which L. acidophilus metabolizes to lactic acid. Lactic acid increases the acidity (lowers pH) of the surrounding environment which in turn inhibits colonization by non-acid forming microbes. The resulting low pH of the vaginal epithelium prevents establishment by most other bacteria as well as the potentially pathogenic yeast such as Candida albicans**. Normal Intestinal Flora in Humans Did you know…? The human body, consisting of about 100 trillion cells and carries about ten times as many microorganisms in the gut. New research out of Stanford shows that there are anywhere from 3,300 to 5,700 different species of microorganisms that populate the gut which justify this microflora as being considered “the neglected organ”. It is estimated the total weight of gut bacteria is about four pounds. As a matter of fact about a third of fecal matter (water removed) consists of dead or viable bacteria. Being that approximately 70 percent of the body’s immune system is gut-based, it is hardly surprising that the GI microflora have a major influence on overall health and disease. In humans, there are differences in the composition of the flora which are influenced by age, diet, cultural conditions, and the use of antibiotics. The latter greatly influences the composition of the gut flora. Oral Cavity (mouth) The oral cavity contains- millions of microbes per 5ml (1 teaspoon) of saliva. The normal bacterial flora of the oral cavity contains between 75 to 100 different microbial species. Many of these microbes clearly benefit from their host who provides a nutritious habitat. There may be benefits, as well, to the host. The normal oral flora occupies available colonization sites which makes it more difficult for other microorganisms (nonindigenous species) to become established. Also, the oral bacteria exert microbial antagonism against non-indigenous species by production of inhibitory substances such as fatty acids, hydrogen peroxide (oxidizer/disinfectant) and bacteriocins (substances released that kill other bacteria). Finally, the oral flora contributes to host nutrition through the synthesis of vitamins, and they contribute to immunity by inducing low levels of circulating and secretory antibodies that may cross react with pathogens. On the other hand, the normal oral flora can also be the usual cause of various oral diseases in humans - including abscesses (infections), dental caries (cavities), gingivitis (inflammation of the gums) and periodontal disease (gum infection resulting in tooth lose). If that wasn’t bad enough if normal oral bacteria gain entrance into deeper tissues, they may cause infections of the jaw bone, lung, heart, brain, or the extremities. Though the oral cavity is teaming with a variety of microbial species, the more common species which can be both helpful as well as hurtful to the host are: – Actinomyces naeslundii **– forms dental plaque by adhering to the surface of the teeth. – Candida albicans** - is a yeast (fungi family) and commensal, living in 80% of the human population with no harmful effects. However, C.albicans is also an opportunistic microbe (potential pathogen) and an agent of oral infections such as thrush. – Corynebacteria species – predominate organism on the skin, but also found in the mouth. Image: Thrush – Bacteroide melaninogenicus ** – cause of periodontal disease. – Fusobacterium** – normal inhabitants of the oral cavity, but can also cause periodontal disease. – Lactobacillus species** - considered as a “friendly bacteria” Lactobacilli are part of a large group of lactic-acid producing bacteria. However, the acid formation can contribute to the formation of dental caries. – Porphyromonas gingivalis** – can cause periodontal disease. – Staphylococci epidermidis - predominate organism on the skin, but also found in the mouth. – Streptococcus salivarius** - is the principal commensal bacterium of the oral cavity in humans. It is the first bacterium which colonizes the dental plaque, before being joined by numerous other species of various genera. – Streptococci mutans ** - another bacterium involved in plaque formation and initiation of dental caries. If oral streptococci are introduced into wounds created by dental manipulation or treatment, they may adhere to heart valves and initiate subacute bacterial endocarditis (infection of heart). – Veillonella** – another bacteria involved in plaque formation. Stomach The stomach contains – less than 100 microbes per 5 ml (1 teaspoon) of stomach liquid. In the upper GI tract of adult humans, the esophagus contains only the bacteria swallowed with saliva and food. Because of the high acidity of the gastric juice (hydrochloric acid HCL), very few bacteria can be cultured from the normal stomach. The acidity of a normal stomach is around pH-3 which kills most microbes. Some evidence exists for pH going below 1.0 to facilitate optimal digestion. However, if microorganisms are acid resistant and survive, they are swiftly moved on to the small intestine by the peristaltic waves which keep the contents of the GI tract moving. Some microbes found in the stomach are: Lactobacillus species – considered as a “friendly bacteria” Lactobacilli are part of a large group of lactic-acid producing bacteria. And are frequently incorporated into probiotic supplements. Helicobacter pylori** - at least half the population in the US is colonized with this potentially pathogenic bacterium which is the cause of ulcers. Small Intestine The small intestine contains – millions of microbes per gram (.03 ounces) The upper portion of the small intestine has a relatively sparse transient flora, consisting mainly of Lactobacilli and Enterococcus faecalis. Also found in the small intestines is the yeast Candida albicans. Lactobacillus species - considered as a “friendly bacteria” Lactobacilli are part of a large group of lactic-acid producing bacteria and by far the most important bacterial resident of the small intestine. This is the colonizer, the inhabitant that constitutes the first line of defense against pathogens. When Lactobacilli bacteria are present in sufficient numbers, they prevent invading pathogens and opportunistic organisms from finding “parking spaces” along the walls of the intestine, where nutrients cross into the bloodstream. Lactobacilli are frequently incorporated into probiotic supplements. Enterococcus faecalis**– normally a commensal bacterium which inhabits the G.I. tract. However, E. faecalis can cause infections in the heart (endocarditis), bladder, and prostate. It is also among the most antibiotic resistant bacteria known. Image: Lactic Acid Candida albicans** - is a yeast (fungi family) and commensal, living in 80% of the human population with no harmful effects. However, C.albicans is also an opportunistic microbe (potentially pathogenic) and overgrowth of this bacterium in the intestines results in a condition called candidiasis (see below). The lower portion of the small intestine contains greater numbers of Lactobacilli species and Enterococcus faecalis as permanent/resident microorganisms along with additional species such as Bifidobacteria and Bacteroides (see large intestine). Large Intestine The large intestine (colon) contains – billions of microbes per gram. The stool contains 100 – 1000 billion microbes per gram. The large intestine is primarily an anaerobic environment – no oxygen is present. This area of the gastrointestinal tract is where the highest concentration of microbes, mostly bacteria, is found. A list of the more common microorganisms found in the large intestines of humans are: Bacteroides species ** - are the most prevalent bacteria found in the colon. Bacteroides assist in breaking down food products and supplying some vitamins and other essential nutrients. Bacteroides are producers of acetic acid and succinic acid. However, they are also opportunistic pathogens and therefore a common cause of endogenous infections. B. fragilis is the most notable pathogen. Bacteroides have also been implicated in the initiation of colitis and colon cancer. Bifidobacterium species – are lactic acid producing bacterium which have been described as “friendly” bacteria and exert a range of beneficial health effects in the intestines of humans. These bacteria are sometimes used in the manufacture of yogurts and are frequently incorporated into probiotics supplements. Bifidobacterium is sometimes referred to as Lactobacillus bifidus. Bifidobacterium is the predominant bacterial species in the intestine of breast-fed infants, where it presumably prevents colonization by potential pathogens. Candida albicans** - is a yeast (fungi family) and commensal, living in 80% of the human population with no harmful effects. However, C. albicans is also an opportunistic microbe (potentially pathogenic) and overgrowth of this bacterium in the intestines results in a condition called candidiasis (see below). Clostridium species ** o C. difficile – may colonize the bowel and cause “antibiotic-induced diarrhea” colitis. o C. perfringens – is commonly isolated from feces and can cause a wide range of symptoms such as food poisoning. o C. septicum – can cause gas gangrene (infection that produces gas in dead tissue) associated with colorectal cancer and other defects of the bowel. o C. tetani – is transiently associated with humans as a component of the normal flora. Ingested with food and water, but the bacterium does not colonize the intestines. It is the causative organism of tetanus (muscle spasms). Enterococcus faecalis ** - the bacterium is such a regular component of the intestinal flora, that many European countries use it as the standard indicator of fecal pollution. However, E. faecalis can cause infections in the heart (endocarditis), bladder, and prostate. It is also among the most antibiotic resistant bacteria known. Enterobacteriaceae (Family) ** - Is a large bacterial family. A number of genera within the family are human intestinal pathogens such as – Salmonella, Shigella, and Yersinia. Several others are normal colonists of the human gastrointestinal tract such as – Enterobacter, Klebsiella, Citrobacter and Proteus species. Though commensal they too like many other species of microorganisms have strains that become opportunistic pathogens when the circumstances are just right. An example of this is Escherichia coli (E.coli). Though most E.coli strains are harmless, some strains are pathogens that cause intestinal infections, urinary tract infections and food poisoning. Lactobacillus species - considered as a “friendly” bacteria Lactobacilli are part of a large group of lactic-acid producing bacteria. And are frequently incorporated into probiotic supplements. Pseudomonas aeruginosa ** - is the quintessential opportunistic pathogen of humans that can invade virtually any tissue. It is a leading cause of hospital acquired infections, but its source is often exogenous. Staphylococcus aureus** - is a leading cause of bacterial disease in humans. Functions of “Friendly” Flora in the Human Gut. Microorganisms, specifically bacteria, in the gut perform a variety of useful functions for humans. Microorganisms in humans which perform useful functions are generally referred to as “friendly” microorganisms. It is commonly recognized that the predominate genus types of friendly bacteria found in the gut flora of humans are – Lactobacilli, Bifidobacterium and Streptococcus. It must be noted that there are numerous species and strains within each genus type of friendly bacteria. Not all of which are friendly, some can even be pathogenic. Therefore attention needs to be taken in considering which species and strains are being identified when talking about “friendly” microorganisms. A list of some of these friendly microorganisms and their vital roles/properties in the human gut are described below. Anti-Biotic, Anti-Viral, and Anti-Carcinogenic Properties Friendly bacteria prevent the colonization (antibiotic property) of pathogens in order to preserve their own territory. Friendly bacteria can do this by several means: 1) 2) 3) 4) Compete with pathogens for attachment sites to intestinal wall. Compete with pathogens for nutrients. Change the local levels of acidity (lower pH) Produce their own antibiotic substances which kill or deactivate pathogenic bacteria. Not all strains of Lactobacilli produce the same benefits. For example it has been found that some strains of Lactobacillus acidophilus, such as DDS-1 can produce powerful antibiotic substances such as acidophilin, lactolin and acidolin whereas other strains cannot. This strain, however, must be derived from a milk medium. Friendly bacteria also have anti-carcinogenic properties and help fight cancer in three ways: 1) Certain super stains eliminate pro-carcinogenic substances before they turn cancerous. 2) By altering potentially dangerous enzymes such as - b-glucuronidase, b-glucosidase, and nitroreductase. These enzymes are produced by pathogenic bacteria which turn pro-carcinogens into carcinogenic agents. Studies show these enzymes are slowed dramatically by the friendly bacterial Lactobacillus acidophilus. 3) By a mechanism that is poorly understood, Lactobacilli and Bifidobacteria have the mysterious ability to directly suppress some tumor activity. The transient bacteria (non-resident) – Lactobacillus bulgaricus and Streptococcus thermophiles (used to make yogurt) have been shown to produce a substance with powerful anti-tumor activity. Lactobacillus bulgaricus also has been shown to have powerful anti-herpes virus effects. Bacteria Anti-Biotic Bifidobcterium bifidum Lactobacillus acidophilus (DDS-1) bifidin acidolin acidophillin lactobacillin lactocidin bulgarican lactobrevin lactolin nisin Lactobacillus bulgaricus (DDS-14) Lactobacillus brevis Lactobacillus plantarum Streptococcus lactis Streptococcus thermophiles Anti-Viral hydrogen peroxide anti-herpes effect Anti-Carcinogenic anti-tumor effect anti-tumor effect anti-herpes effect anti-tumor effect Chart: Anti-biotic, Anti-viral and Anti-carcinogenic properties of the most common friendly microorganisms found in the human gut. “Natural” Antibodies The normal gut flora stimulate the production of “natural” antibodies. Since the normal gut flora behave as antigens they induce an immunological response, in particular, an antibody-mediated immune response. Antibodies are proteins produced, by the immune system, to neutralize pathogens or antigens. Low levels of antibodies produced against components of the normal gut flora are known to cross react with certain related pathogens, and thereby prevent infection or invasion. Antibodies produced against components of the normal gut flora are sometimes referred to as "natural" antibodies. Carbohydrate Fermentation The normal resident gut flora ferments substances that cannot be digested by the host in the small intestine. These substances include resistant starch, non-digestible carbohydrates and other improperly digested foodstuff. One of the main types of fermentation that is carried out in the gut is - saccharolytic fermentation/carbohydrate fermentation. In general fermentation typically is the conversion of sugars and other carbohydrates to ethanol/alcohol and carbon dioxide or organic acids. More specifically, fermentation can refer to yeast microorganisms converting sugar/carbohydrates to alcohol and carbon dioxide. Or it can refer to bacterial microorganisms converting sugar/carbohydrates to organic acids. Some of the organic acids produced in the fermentation process via anaerobic friendly bacteria are: Acetic acid (acetate) – a short chain fatty acid (SCFA) which is used by muscles, kidneys, heart and brain for energy production. [produced by: bacteroids, bifidobacteria, lactobacilli, clostridia, eubacteria, ruminococci, peptococci, veillonella, fusobacteria, peptostreptococci, propionicbacteria, butyrivibrio] Propionic acid (propionate) – a SCFA which is transported to the liver where it helps the liver produce ATP and it may interfere with cholesterol synthesis. [produced by: bacteroides, propionbacteria, veillonella] Butyric acid (butyrate) – a SCFA which is the preferred fuel for the mucosa. Epithelial cells lining the colon obtain up to 70% of their energy from SCFAs. Butyric acid may also prevent cancer. [produced by: clostridia, fusobacteria, butyrivibrio, eubacteria, peptostreptococci] Lactic acid (lactate) – lowers pH of surrounding area making it uninhabitable for pathogenic microorganisms. [produced by: bacteroides, bifidobacteria, lactobacilli, clostridia, enterococci, actinomycetes,eubacteria, peptostreptococci, ruminococci, fusobacteria] Digestion Normal friendly bacteria manufacture the milk-digesting enzyme lactase which helps digest dairy products. However, the production of lactase by friendly bacteria will not digest casein, a milk protein. They improve the efficiency of the digestive tract and bowel function. Manufacturing and Absorption of Nutrients Normal friendly bacteria manufacture some of the vitamins including - vitamin K, vitamin B12, niacin (B3), pyridoxine (B6), folic acid and biotin. They also increase the bioavailability (absorption) of vitamins, minerals and protein in the GI tract. This is a result of increased acidification of the gut pH by the lactic acid producing bacterial. Other Functions It has been hypothesized that friendly gut bacteria can help to turn off the inappropriate, over-reactive immune response of inflammatory bowel disease (IBD). Lactobacilli are useful in irritable bowel syndrome (IBS), a condition that is characterized by abnormal muscle contractions of the bowels. This is because Lactobacilli release several amino acids, including tryptophan, which produces the calming neurotransmitter serotonin. Due to its production of tryptophan to serotonin, in sufficient numbers Lactobacilli can also encourage a relaxed state and be of benefit in anxiety disorders. Friendly bacteria effectively help to reduce cholesterol levels when this is high. Intestinal Dysbiosis and Toxic Intestinal Byproducts Dysbiosis is a term used to describe an imbalance between the number or ratio of pathogenic to friendly microorganisms within the human gut. Dysbiosis is a state of living with an over abundance of pathogenic intestinal microorganisms/flora that have harmful effects on the body. The state of dysbiosis within the gut produces a number of toxic intestinal byproducts which are then absorbed and sent to the liver - the body’s primary detoxification organ. A healthy liver neutralizes these toxins, and then either recycles them for use in the body or excretes them. However, there are several conditions in which these toxic intestinal byproducts are unable to be properly detoxified by the liver: 1) If the state of dysbiosis within the gut is severe and produces an extremely high amount of toxic byproducts thereby over loading the liver’s detoxification capacities. 2) If the liver is unhealthy with a compromised detoxification system due to – illness, infection, improper diet or drug/alcohol abuse. 3) If the liver is deficient in the proper enzymes needed for the conversion or detoxification of toxic substances. These enzyme deficiencies can be due to genetics, nutritional deficiency, heavy metals, chemical exposures, etc. Regardless of the cause, the liver’s inability to properly detoxify toxic intestinal byproducts results in unprocessed toxic compounds entering into the bloodstream and invading every body systems. The most susceptible body systems are the nervous, endocrine and immune systems. The list of symptoms associated with intestinal dysbiosis and toxic intestinal byproducts is long and ranges from –chronic fatigue, multiple chemical sensitivity, cognitive dysfunction, hormonal imbalance, immune imbalance as well as gastrointestinal disorders, muscle and joint pains. There are numerous causes and conditions which are responsible for the development of intestinal dysbiosis and the production of toxic intestinal byproducts. These causes and conditions are described in detail below. Protein Fermentation (Bacterial) Above we discussed one of the main types of fermentation that takes place in the gut – saccharolytic/carbohydrate fermentation. This type of fermentation was found to produce useful byproducts for the host. However, the same cannot be said for the second major type of fermentation that takes place in the gut – proteolytic or protein fermentation. “The products of carbohydrate metabolism are thought to benefit the host as compared to the toxic end products of protein metabolism” (Hughes) Sources of protein in the colon include dietary residues (major source), pancreatic enzymes, mucins (proteins found in mucus) and exfoliated epithelial cells. The major producers of these proteolytic metabolites are the Bacteroides species of bacteria though Clostridia, Enterobacteria, Bifidobacteria and Lactobacillus species are also involved. The end products or metabolites of protein fermentation include nitrogenous metabolites, some of which are carcinogenic. Many of these metabolites are physiologically active in host tissues, with ammonia, amines, phenols, and indoles being of particular toxicological significance. Ammonia: Ammonia is a nitrogen waste byproduct of protein metabolism. In the intestines proteins are first broken down into amino acids then the amino group is removed prior to energy conversion. The amino group (NH2) combines with a hydrogen ion (H) to form ammonia (NH3). Ammonia is very toxic to the body and is therefore converted by the liver through a series of reactions known as the urea cycle into non-toxic urea, which is then eliminated in the urine. Over 70% of endogenously produced ammonia originates from bacterial degradation of proteins in the colon. Problems arise when ammonia is allowed to accumulate either in the gut or in the blood stream due to the livers inability to convert it to urea and thereby creating a condition known as hyperammonemia. Within the large intestine ammonia exhibits a number of effects that suggest it may be involved in tumor promotion such as - alterations in the morphology and metabolism of cells lining the colonic mucosa, as well as increasing DNA synthesis and affecting their lifespan. Hepatic encephalopathy – is a neurological disorder caused by the livers inability to clear, convert or detoxify toxins such as ammonia. Symptoms range from – loss of cognitive function, confusion, inability to concentrate, lethargy, depression, twitching, slurred speech, slowed or sluggish movements, and subtle personality changes. Amines: Are a class or family of chemical compounds which contain nitrogen. Amines are derivatives of ammonia, where one or more of the hydrogen atoms have been replaced with a substitute atom. Amines have strong odors and is often described as “fishy” since the odor of raw fish comes from the amines contained. Amines found in gut contents include – amino acids, agmatine, tyramine, pyrrolidine, piperidine, cadaverine, putrescine and 5-hydroxytryptamine (precursor to serotonin). The accumulation of amines, due to their failure to be properly excreted (feces) or detoxified via the livers sulfation pathway, has resulted in them being implicated in - hepatic encephalopathy, migraine, schizophrenia and heart failure. Phenols: Are a class or family of chemical compounds consisting of a hydroxyl group (-OH) bonded directly to an aromatic ring. Phenols are produced endogenously as a breakdown product of protein metabolism by the action of bacteria on the aromatic amino acids – phenylalanine, tyrosine and tryptophan – which are normal constituents in the diet. The degradation products include the phenols: p-cresol, phenylpropionate, phenylacetate, indole propionate and acetate. The accumulation of phenols, due to their failure to be properly excreted (feces) or detoxified via the livers sulfation pathway, has resulted in them being implicated in – bladder and colon cancer, schizophrenia and migranes. Indoles: Indole can be produced by bacteria as a degradation product of the amino acid tryptophan. It occurs naturally in human feces and has an intense fecal odor. The accumulation of indoles, due to their failure to be properly excreted (feces) or detoxified via the livers has resulted in them being implicated in – bladder & colon cancer, schizophrenia and migranes. Constipation: Protein breakdown and fermentation in the colon are increased if there are low levels of fermentable carbohydrates available and by long intestinal transit times - constipation. Interestingly, the upper (proximal) colon is essentially a site of carbohydrate fermentation, whereas the lower (distal) colon sees more protein fermentation. This may be one reason why many gastrointestinal disorders occur distally in the lower colon. Putrefaction Putrefaction is the decomposition of organic matter, especially protein, by microorganisms, resulting in production of a foul-smelling matter. Putrefaction takes place when peristalsis is slowed or interrupted (constipation) and food becomes stagnant and may putrefy. This stagnant, rotting food becomes fertile ground for the overgrowth of yeast (candida) and harmful bacteria. Hypochlorhydria Hypochlorhydria is the state where the body is unable to produce the required amount of hydrochloric acid (HCL) in the stomach for the proper digestion of foods, especially of proteins. The stomach requires an acid environment for several reasons: HCL is required for the proper digestion of proteins. Improper digestion of proteins leads to a higher level of protein fermentation in the intestines which produces higher levels of – ammonia, phenols, amines & indoles – which can overload the livers detoxification system and create a condition of hepatic encephalopathy. Improper digestion of proteins can also increase the level of putrefaction in the intestines thereby creating a fertile environment for the growth of pathogenic bacteria and yeast. HCL is required for the stomach to empty correctly. Failure to do so results in gastro-esophageal reflux disease (GERD). HCL is required to sterilize the stomach and kill bacteria and yeast which may have been ingested with food. Low levels of HCL raise the pH of the stomach and creates a fertile environment for the growth of pathogenic bacteria and yeast. An overgrowth of pathogenic bacteria and yeast in the stomach will result in the fermentation and putrefaction (produce gases, alcohol) of foods as opposed to their digestion. HCL is required for the proper absorption of certain vitamins and minerals. Failure to absorb nutrients will lead to nutritional deficiencies such as B-12, boron, calcium, magnesium, zinc, copper, iron, selenium, etc. D-Lactic Acidosis The production of lactic acid in the gut has demonstrated numerous health promoting benefits. Lactic acid is also found in many foods and beverages as well as in probiotic supplements. However, D-Lactic Acidosis is a condition where there is an increase of lactic acid in the blood which causes harm to the body’s tissues, especially the nervous system. D-lactic acidosis causes symptoms such as: Brain fog Poor memory Poor balance Inability to multi-task Inability to perform higher executive functions Confusion Poor word finding Slurred speech Fatigue Muscle pain Lactic acid producing bacterial fermentation produces two isomers of lactic acid, namely L-lactate and D-lactate (an isomer is a variation in the arrangement of atoms in two or more otherwise similar chemical compounds). In the “normal” gut D-lactic acid from ingested food or from the fermentation of sugars is a substrate that is utilized by other bacterial species in the distal gut. Thus little will be absorbed over the gut wall. The lactic acid which does make it over the gut wall is broken down or metabolized in the liver by the enzyme lactate dehydrogenase. These enzymes are also found in the brain and skeletal muscles (places of high energy turn over). However, lactate dehydrogenase only breaks down L-lactate. Mammalian tissues do not have an enzyme which will metabolize D-lactate. Therefore, it is up to the body to slowly metabolize D-lactate. In “normal” humans D-lactate is found in the blood and urine. Normal levels in the blood can range from 0.02-0.25mM. A study of D-lactic acid intestinal bacteria in Chronic Fatigue Syndrome patients confirms that there are significantly more bacteria that produce D-lactic acid in their gut compared to controls. The D-lactic acid producing bacteria found in the CFS study were – Enterococcus faecalis and Streptococcus sanguinis. “This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptoms expressions in a subgroup of patients with CFS” (Sheedy) “When too much fermentable fiber shows up in the large intestine there is a massive uptick in the production of D-lactate. Since, in CFS, we now know there is already overproduction of D-lactate the blanket statement to eat more fiber may not be well suited for CFS. For example, animal studies show that excessive D-lactate production, due to excess fermentable carbohydrates showing up in the distant portions of the gut, can increase aggressive and anxious behavior. It completely throws them off” (Logan) Lactobacillus acidophilus and other lactic acid producing bacteria have also been shown to contribute to D-lactic acidosis. Producing a list of lactic acid producing bacteria and their corresponding lactic acid isomers – D, L, and DL lactate – may be irrelevant because: “It has been shown that addition of large doses of a purely L-lactic acid producing bacteria, Bifidobacterium bifidum could, in fact affect the other colonic bacterial populations such as to increase the level of D-lactic acid produced. A high level of L-lactic acid in the colon is expected to induce an increased D-lactate level through the activity of bacterial DL-lactate racemase. A similar effect could be obtained by the addition of a DLlactic acid producer like – Lactobacillus acidophilus. Thus, ingestion of L-lactic acid producing bacteria can also lead to elevations of D-lactic acid in the human gut.” (Connolly) Along with probiotic supplements, many fermented foods including yogurt, kefir, pickles and sauerkraut as well as cheese, meats and sausages contain D-lactate derived from the lactic acid producing bacteria involved in the fermentation. Studies have shown yogurt to have high concentrations of D-lactate >40%. Also, lactic acid gets in the way of kidney’s excretion of uric acid. High levels of uric acid in the body are the cause of the very painful condition called Gout. Sulfate-Reducing Bacteria Sulfate-reducing bacteria are those bacteria that obtain their energy by reducing sulfates to sulfides, especially to hydrogen sulfide. In a sense they “breath” sulfate rather than oxygen and expel sulfides rather than carbon dioxide. Most sulfate-reducing bacteria can also reduce other oxidized inorganic sulfur compounds such as sulfite. In the gut, the predominate sulfate-reducing bacterium are – Desulfovibrio, Desulfobacter, Desulfomonas, Desulfobulbus and Desulfotomaculum speicies. And the predominate byproduct of these bacteria is hydrogen sulfide which is both very noxious to the colonic epithelium and a potent neurotoxin and therefore is implicated in: Mitochondrial dysfunction Depressed immune system Cognitive dysfunction, dizziness, faintness Noise and light sensitivities Heart Palpitations Ulcerative colitis Impaired liver detoxification Hypothalamic-Pituitary dysfunction Sleep disturbance Pain/Myalgia Inflammatory bowel disease (IBD) Researchers have shown that people with Chronic Fatigue Syndrome consistently have higher levels of hydrogen sulfide compared to normal controls. The chief source of sulfur in the diet is derived from dietary inorganic sulfur (sulfate, sulfite) and the sulfur amino acids – methionine, cysteine, cystine, and taurine – found in protein foods. Not to mention the sulfur compounds used for preservatives in much of today’s western diet foods. Sulfate can also be produced as a byproduct from other intestinal bacteria such as Clostridia, Bifidobacteria and Bacteroide species. Dietary sulfate may allow growth of sulfate reducing bacteria, which competes with and inhibits the growth of beneficial bacteria. Therefore, caution needs to be taken when eating foods high in sulfate or taking supplements with sulfate (i.e. glucosamine sulfate). Candidiasis: Candidiasis is a fungal infection of any of the Candida species of which C. alibicans is the most common. C. albicans is a yeast and therefore Candidiasis is commonly referred to as a yeast infection. Candida albicans is present in every adult and in most children on the planet within a short time after birth. It normally does no harm (commensal), for it is kept in check by the alert immune system as well as by a variety of other friendly microorganisms (i.e. lactobacilli). The candida genus is comprised of 200+ known species with over 40 of them known to cause human infections. Of these, the 8 common species of candida account for over 90% of the infections found in humans. These 8 are: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae, C. kefyr. Of these 8 species of candida, C. alibicans is responsible for over 85% of fungal infections in humans. Candida organisms can spread out from the lower bowel to colonize the entire digestive tract, including up through the stomach (especially in cases of low or no stomach acid- HCL) into the throat, mouth and nasal passages, and down into the lungs. Anatomy Fungi Oral Cavity Candida sp. Stomach Intestine C. albicans C. kruzei C. tropicalis C. glabrata C. lusitaniae Saccharomyces sp. Candida sp. Colon Candida sp. Prevalence 52-62% 75% in elderly population 31.3% 23.1% in healthy people 38.8% in IBD (irritable bowel disease 1.3% in health people 13.8 – 33.3 in IBD Chart: Prevalence of fungi in the gastrointestinal tract: Candida albicans and Candida kruzei were found to multiply in pH of 2.0. Previously, it was generally accepted that bacterial and yeast overgrowth was not possible in gastric pH<4.0. Results from both in vitro and in vivo studies revealed that a variety of bacteria and yeasts are able to survive and multiply in environments as low as pH 3.0 Candida albicans produces several byproducts as a result of its metabolism. Two of the more commonly studied byproducts are ethanol/alcohol and acetaldehyde. Both of these candida byproducts are toxic to the body. If not handled properly by the liver (detoxified) they will make their way into the blood stream and to the rest of the body where they will cause damage. These toxic byproducts and the damage they can cause are discussed in more detail below. Ethanol/Alcohol: In healthy individual’s ethanol from candida metabolism can be detected in the blood but it is at a level that doesn't cause any problems as the body’s detoxification systems can cope with it. In healthy individuals ethanol is converted into acetaldehyde via the enzyme – alcohol dehydrogenase. If however, the liver is unable to detoxify ethanol it will build-up and become toxic to the body. Ethanol/alcohol is the same chemical contained in beer, wine, and liquor that gets into the brain and causes a person to become intoxicated – drunk. A chronic case of candidiasis will produce a similar low level intoxication affect. The state of candidiasis produces a steady stream of alcohol which will be absorbed and sent to the liver. This becomes a burden for the liver and may cause liver dysfunction. This in turn will mean a steady stream of alcohol being released into the blood and reaching the brain causing low levels of intoxication along with its corresponding symptoms. Acetaldehyde: Acetaldehyde is a direct byproduct of Candida albicans as well as an indirect byproduct via C. albicans production of ethanol which is then converted to acetaldehyde. Regardless, acetaldehyde is extremely toxic to the body. It is produced in the gut, absorbed by the intestinal wall and enters into the portal circulation where it is then carried into the liver. Along the way acetaldehyde can cause various types of damage due to acetaldehyde’s ability to bind to sulfhydryl and amine sites on proteins. Acetaldehyde exerts its damage by altering membrane rigidity. Research has demonstrated increased rigidity of erythrocyte (Red Blood Cells) membranes in patients with candidiasis. It could be implied that a similar abnormality of cell membranes exist throughout the body. This could then furnish one possible mechanism for the multi-system nature of symptoms exhibited by patients with candidiasis. Numerous studies have demonstrated impairment of transport into and out of the cells when membranes become more ridged. Indeed, the status of erythrocyte membrane flexibility has been found to correlate with that of membranes in the liver and other organs. “Therefore, the presence of acetaldehyde in the intestine, the intestinal wall, and the portal blood would afford many opportunities for its binding to such substances as nutrients, enzymes, vitamins and polypeptides. If formed high enough in the intestinal tract, acetaldehyde could react with digestive enzymes in the small intestine. The possibilities are many” (Truss). “The ultimate effect of this very toxic substance could include disruption of intestinal absorptive processes, as well as impairment of function in erythrocytes, leukocytes and other cells in which it accumulates” (Truss) “Among the functions impaired by membrane rigidity are functional impairment of membrane-bound enzymes, of amino acid transport, of glucose transport, of facilitated diffusion, of Na+-K+ ATPase function, of mitochondrial enzyme function and the function of the Ca2+ ATPase pump in the endoplasmic reticulum” (Truss). Once acetaldehyde finally enters into the liver (after doing its damage) it is further reduced by the enzyme – aldehyde dehydrogenase/ALDH2 to carbon dioxide, water and acetyl coenzymeA. Carbon dioxide and water are eliminated from the body, whereas acetyl CoA can be: (a) used immediately for energy production or (b) converted to fatty acids that are stored by the body and used later for energy or (c) converted into the neurotransmitter acetylcholine. Aldehyde dehydrogenase is a molybdenum (trace mineral) containing enzyme. Molybdenum is also needed for two other enzymes in the body: (1) Sulfite oxidase - which is used in the liver’s sulfoxidation detoxification pathway to convert toxic sulfites to the safer sulfates. (2) Xanthine oxidase- which converts xanthine to uric acid. Molybdenum is a trace mineral, meaning it is found in limited amounts in foods and in the body. Because of this limited supply molybdenum can quickly become depleted in the body through its use by the three molybdenum containing enzymes. If this occurs, aldehyde dehydrogenase will be unable to reduce acetaldehyde thus causing it to build-up in the body and creating even more damage. Acetaldehyde is also the chemical responsible for the main symptoms of a hangover. Leaky Gut Syndrome/Intestinal Permeability: Candida albicans is a dimorphic organism, which means that it can exist either as a commensal round yeast cell or it can change its form or morph into a pathogenic fungus with spindly outgrowths called hyphae. In the fungal form the hyphae can multiply into bundles called mycelia. Mycelia can then penetrate the body tissue of the host by putting down rhizome roots into the surrounding mucous membrane. Candida has the ability to morph between yeast and fungal depending on what is happening in the body. When the mucous membrane lining is penetrated by rhizomes the gut becomes more permeable causing Leaky Gut Syndrome/Intestinal Permeability. Leaky Gut Syndrome makes it possible for partially digested food particles, toxic wastes, and yeast break down products to pass through and into the bloodstream. This causes a tremendous load on the liver and its detoxification system. It can also result in allergies, sensitivities and a constant drain on the immune system. Also, with Leaky Gut Syndrome, candida albicans yeast cells themselves, may actually be able to slip through and gain access to the rest of the body, via the blood stream, thereby becoming a “systemic candida infection”. Liver Dysfunction: When an overabundance of food particles, toxic waste and yeast byproducts are able to freely make its way to the liver, due to Leaky Gut Syndrome, this will over tax the livers capacity and cause it to dysfunction. This means toxic substances will not be detoxified and will make their way into the rest of the body’s tissues causing harm. Alcohol, either produced by candida or drunk as a beverage, once absorbed heads straight to the liver via the portal vein. One of the things alcohol does is makes the Kupffer cells in the liver “sleepy”. The Kupffer cells, lining the hepatic sinusoids of the liver, constitute about 90% of all the macrophages (immune cell) in the human body. If the Kupffer cells get “sleepy”, the portal blood flow from the intestine, loaded with foodstuff and chemicals will not be properly detoxified by the liver. This means unfiltered blood will make its way into the general circulation and causing damage to the body’s cells. Once Candida albicans itself enters into the blood system the first organ to be invaded is the liver, via the portal vein. If the liver is dysfunctioning the yeast cells can easily spread to the lungs, heart and other organs and thereby becomes a systemic infection – systemic candidiasis. Damage to the liver is often an underlying factor in chronic candidiasis. To a large extent the health vitality and energy levels of an individual are determined by the health and vitality of the liver. The liver is without question the most important organ of metabolism. The health and function of the liver is critically linked to the status of the immune system. When the liver is even slightly damaged by toxins, immune function is severely compromised. Immune Dysfunction: Once toxic intestinal byproducts (food particles, toxic waste, yeast byproducts) make their way into the blood stream, due to Leaky Gut Syndrome, this will result in allergies, sensitivities and a constant drain on the immune system causing it to dysfunction. Once Candida albicans itself enters the bloodstream (systemic candidiasis), the pH of the bloodstream is very pH neutral, which is very conducive for the fungal form of candida to grow. Once candida becomes systemic it is very difficult to eliminate. Candida secrets an enzyme – aspartyl protease – which cleaves off receptors on white blood cells (WBCs) which are used to recognize pathogens. This results in the candida being able to hide from the immune system. But the cleaving of WBC receptors also results in immunosuppression. This is because the WBC receptors are used to attach to the walls of the bloodstream and then enter into the tissue where there may be an infection. Though neutrophils (a macrophage involved in primary defense against infection) tend to be the most effective white blood cells against candida, the fungal form of candida has been shown to suppress, evade and even destroy macrophages. Candida albicans secrets into the blood stream a large number of substances which include toxins (mycotoxins), enzymes, and other foreign proteins which all act as antigens and promote an immune response against them. C. albicans is referred to as a poly antigenic organism because over 79 distinct antibodies are produced by the immune system against these substances. Because of the tremendous number of antigens, an overgrowth of C. albicans greatly taxes the immune system and it has been demonstrated this effect causes suppression of the immune system. Candida has the ability to continually shift its outer membrane so that the immune system will have trouble recognizing it. Candida, like all infections has the ability to surround itself with a biofilm. Thereby again hiding from the immune system. Because 70 % of the immune system is in the gut, if something goes wrong in the gut it will affect the immune system. And anything that will affect or suppress the immune system (chemical body burden, drugs – antibiotics, etc.) will cause a change in the intestinal environment by allowing pathogenic microbes to proliferate. Candida is the fourth most common hospital acquired infection. Endocrine Dysfunction: Candida albicans and its byproduct acetaldehyde interfere with normal hormone metabolism; it affects pituitary, thyroid and adrenal glands. Candida albicans and acetaldehyde block cell membranes and so competes with: Thyroxin (thyroid hormone) – a person may have normal blood thyroid hormone levels even though their basal metabolic rate is low. Thyroxin cannot get into cells because of chronic acetaldehyde poisoning. Cortisol (adrenal hormone) - Candida albicans has a steroid-binding protein. Candida albicans attaches itself to adrenal steroids, like cortisol, causing adrenal insufficiency/adrenal fatigue. Progesterone - Candida albicans has a steroid-binding protein. It binds with corticoids and progesterones. Estrogen – Candida albicans has an estrogen-binding protein. This leads to low cell estrogen while maintaining normal blood estrogen levels. “We and others have demonstrated the presence in several fungi of steroid-binding proteins (SBPs) that exhibit high affinity and specificity for vertebrate steroid hormones. A corticosteroid-binding protein showing high affinity for both corticosterone and progesterone has been described in Candida albicans. An estrogen-binding protein has been demonstrated in Candida albicans, Saccharomyces cerevisiae and Paracoccidioides brasieliensis.” (Malloy) It is theorized that the immune system, confused by the steroid-binding protein of the yeast, begins to mark steroids or hormones produced by the endocrine system that have bonded with the yeast protein. Researchers have noted a group of disorders arising from autoimmune dysregulation associated with Candidiasis referred to as - autoimmune polyendocripopathy immune-dysregulation candidosis hypersensitivity syndrome. Among the related conditions of this syndrome are: hypothyroidism, thyroiditis, hypoadrenalism, Addison's disease, hepatitis, premenstrual syndrome, and rheumatoid arthritis. Although the mechanism is not clearly understood, these conditions seem to be triggered by toxins associated with candidaisis or systemic yeast infections. It has been speculated that because both acetaldehyde and insulin are released into the portal blood that acetaldehyde will bind with insulin’s sulfhydryl and amine protein receptors. Thereby impairing insulin and contributing to the development of type II diabetes. “Insulin resistance is the hallmark of type II diabetes. Since this was present in all degrees of severity in these patients (candidiasis), it strongly suggests that Candida albicans may at least be an aggravating factor in this condition.” (Truss) Parasites In addition to bacteria and yeast, most of the world's four billion people are also colonized by intestinal parasites. Contrary to popular belief, parasitic infection is not unusual in the U.S. population. It is a common occurrence, even among those who have never left the country. Unlike bacteria and some yeast, parasites appear to serve no useful function. The part of the immune system which they stimulate does not strengthen the organism to resist serious infection; instead it contributes to allergic reactions, so that parasitic infection increases allergic tendencies. There are two general groups of parasites. The first consists of worms--tapeworms and roundworms--which attach themselves to the lining of the small intestine, causing internal bleeding and loss of nutrients. People infested with worms may have no symptoms or may slowly become anemic. The second category is the protozoa, one-celled organisms such as: Giardia lamblia which causes diarrhea impairs digestion and absorption. Results from this damage can cause chronic fatigue and other symptoms. Cryptosporidium which recently achieved notoriety for contaminating Milwaukee's water supply, causing the largest epidemic of diarrhea in U.S. history, infecting 400,000 people and causing over one hundred deaths. Most municipal water supplies in the U.S. today are home to protozoa like Giardia and Cryptosporidium and one in five Americans drinks water that violates federal health standards. Every year, almost a million North Americans become sick from water-borne diseases; about one per cent die. How parasites make people sick is not clear. Some directly invade the lining of the intestine, others provoke an allergic reaction that causes the damage. It appears certain that humans coexist quite readily with their parasites as long as the barrier formed by the intestinal lining remains fully intact, so that the parasites cannot attach to the wall of the bowel. For example millions of people throughout the world are carriers of E. histolytica; the organism can be found in stool samples but it does not seem to make them ill. Antibiotics Once one gets an infection of any type… the normal protocol is to give antibiotics. But antibiotics are especially effective in disrupting the gastrointestinal/gut ecologic equilibrium, and oral antibiotic therapy in humans often leads to colonization and overgrowth of the gut by Candida albicans. Antibiotics promote yeast growth by: Antibiotics destroy competitive inhibition by destroying bacterial colonies, thus they create space for the growth of other organisms like candida albicans, a yeast which is not affected by the antibiotics. Antibiotics destroy bacterial colonies that secrete acids that maintain the intestinal pH of the digestive tract in its normal proper range of 1-2. When intestinal pH gets over 6.5 this will trigger the growth of C. albicans to morph into its pathogenic fungal form. Antibiotics destroy bacterial colonies that secrete fatty acids that have antifungal properties and inhibit candida yeast from morphing into its pathogenic fungal form. Fatty acids such as butyric acid while being the main source of energy for intestinal cells also protect the intestinal cells by inhibiting fungal growth. Antibiotics destroy bacterial colonies causing the release of their internal components such as peptidoglycans which directly triggers yeast to convert to its pathogenic fungal form. Antibiotics have been shown to inhibit both antibody synthesis and phagocytic activity and this may reduce the host resistance to invasion by C. albicans. Antibiotics suppress macrophages (WBCs) which can engulf yeast buds and prevent them from morphing into fungal candida. Antibiotics suppress cytokines that recruit neutrophils, which inhibit fungal candida. Neutrophils are the body’s main defense against candida. Antibiotics suppress cytokines which induce the immune/inflammatory response. This allows C. albicans to grow unchecked by the immune system. Suppressing the immune/inflammatory response also suppresses the liver from releasing substances whose job it is to bind with iron so it is not available for pathogens (bacteria, yeast) which need iron to survive. Antibiotics directly stimulate the yeast-to-fungus conversion. One of the antibiotics that’s been shown to do this is tetracycline… thought they don’t know why. Research shows that 30% of gut flora is whipped out after antibiotic treatment and much of it doesn’t return. Other Factors: Fast paced lifestyle Intense physical exercise Emotional traumas Lack of relaxation/ Poor sleep High sugar intake Eating fast foods Eating on the run Foods containing antibiotics Foods containing hormones Steroids Birth control pills Cortisone Prednisone Intestinal Dysbiosis: Pharmaceutical Treatments Treatment for intestinal dysbiosis, caused by bacterial, fungal or parasitic overgrowth (or all the above) can be difficult and confusing. There are fungal medications and parasitic medications that may be valuable in eradicating these microorganisms. However, as just mentioned, antibiotic medications are not recommended due to the fact that antibiotics are a major cause of gut dysbiosis. Anti-Fungal Pharmaceuticals (internal use) Unlike bacteria, both fungi and humans are eukaryotes – organisms whose cells contain organelles enclosed within membranes. Thus fungal and human cells are similar at the biochemical level. For example fungus cell membranes contain ergo-sterol while human cell membranes contain chole-sterol. This makes it more difficult to find or design drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly. Thought there are dozens of antibacterial drugs available, there is a limited amount of antifungal drugs available for internal use. The most common anti-fungal drugs are listed below. Mycostatin/Nystatin (approval date 1965) – is a narrow spectrum antifungal medication, meaning it is effective with some strains of Candida albicans but not all. Although nystatin is relatively free of side effects as compared to other drugs it is derived from mold, so it could give a mold sensitive individual an allergic reaction. Nystatin only works in the intestinal tract and therefore is not used to treat systemic candida. Nystatin supposedly does not enter the blood stream though there is research showing some liver toxicity. It is not unreasonable to assume that as with antibacterial antibiotics, an increased use of nystatin will induce the emergence of nystain resistant strains of candida. Drug resistance simply means that the organism involved has adapted to the drug and is no longer affected by it. Pyrimidines: Ancoban/Flucytosine (approved 1972) – this drug is hampered by its somewhat limited spectrum of activity and its significant potential for toxic effects – vomiting, diarrhea, and liver dysfunction. In addition, emergence of resistance during flucytosine therapy, especially among candida species, is a troublesome feature. Polyenes: Fungizone/Amphotericin B (approved 1958) – a broad spectrum antifungal medication. Administered intravenously, though capsules are available in Europe, but have not been approved for use in the U.S. Some oral forms of pure amphotericin B are available at a few specialized compounding pharmacies in the U.S. The oral form of this drug is similar to nystatin as it is chemically related. And as with nystatin it is not absorbed from the intestine in any significant amount so again is very safe. The intravenous form, however, is very toxic to the body. “Although conventional amphotericin B (Fungizone) remains the standard therapy for many invasive or life-threatening mycoses, this polyene drug is associated with significant toxicity. In addition, the clinical efficacy of amphotericin B in some settings is suboptimal.” (Dismukes) Consequently, three new lipid formulations of amphotericin B have been developed and approved by the FDA: 1. Abelcet/Amphotericin B [lipid complex] (approved 1995) 2. Amphotec/Amphotericin B [cholesteryl sulfate] (approved 1996) 3. AmBisome/AmphotericinB [liposomal] (approved 1997) These lipid formulations offer several advantages over conventional amphotericin B, including increased daily dose of the parent drug (up to 10-fold); high tissue concentrations in the lungs, liver, and spleen; decrease infusion-associated side effects; and marked decrease in nephrotoxicity (kidneys). Although the therapeutic toxic ratio of these compounds is clearly improved, superiority in clinical efficacy has not been definitively established in head to- head comparative trials. Moreover, these lipid formulations of amphotericin B are considerably more expensive than conventional amphotericin B, ranging from 10- to 20-fold higher in cost per dose. Azoles: A potential limitation of the azole family of antifungal medications is the emergence of resistance of fungal organisms, especially candida species to fluconazole/diflucan. Nizarol/Ketoconazole (approved 1981) - a broad spectrum anti-fungi medication used for systemic candida. Ketoconazole inhibits the fungal p450 enzyme 14 alpha-demethylase and stops the cells from making ergosterol, the main component of the fungal cell wall. The medication is somewhat better absorbed orally when it is taken with a fatty meal or acidic drink (e.g. orange juice). It is bound to proteins such as albumin in the circulating blood and is widely distributed in body tissues. It takes three to ten hours for half of the medication to be cleared from the blood stream. The rest is eliminated in feces and urine either unchanged or after conversion by the liver into inactive compounds. Due to frequent cases of liver damage oral ketoconazole is less often prescribed than in past years, because the newer azole drugs, itraconazole and fluconazole, are less likely to upset liver function. Diflucan/Fluconazole (approved 1990) - a broad spectrum of anti- fungi medication used for systemic candida. Fluconazole inhibits the fungal p450 enzyme 14 alpha-demethylase and stops the cells from making ergosterol, the main component of the fungal cell wall. Fluconazole is well absorbed orally with or without food. It is widely distributed in body tissues. It takes 22 to 30 hours for half of the medication to be cleared from the blood stream and may take several days of continuous treatment to reach a steady concentration. The drug is eliminated unchanged in the urine so doses should be reduced if there is kidney disease. Sporanox/Itraconazole (approved 1992) – a broad spectrum anti-fungi medication used for systemic candida. Itraconazole inhibits the fungal p450 enzyme 14 alpha-demethylase and stops the cells from making ergosterol, the main component of the fungal cell wall. Taken in capsule form and is fully absorbed in the upper digestive tract. The medication is better absorbed orally when it is taken with a fatty meal or acidic drink (e.g. orange juice). It is bound to proteins such as albumin in the circulating blood and becomes concentrated in fat cells and within skin and nails. It takes one to three days for half of the medication to be cleared from the blood stream. The rest is eliminated in feces and urine after conversion by the liver into inactive compounds. Selected pharmacologic properties of 200mg of oral azole agents Dose Fluconazole Itraconazole Ketoconazole Oral bioavalability (%) Peak plasma concentration (ug/mL) Time to peak plasma (hr.) Protein binding (%) Spinal fluid penetration (%) Half-Life (%) Active drug in urine (%) >80 10.2 >70 0.2-0.4 >75 1.5-3.1 2-4 11 >70 22-35 80 4-5 >99 <1 24-42 <1 1-4 99 <10 7-10 2-4 Vfend/ Voriconazole (approved 2002) – a chemically related to fluconazole, it is a broad spectrum of anti-fungi medication used for systemic candida. Voriconazole inhibits the fungal p450 enzyme 14 alpha-demethylase and stops the cells from making ergosterol, the main component of the fungal cell wall. Allylamine: Lamisil/Terbinafine (approved 2000) – inhibits ergosterol synthesis by inhibiting a different enzyme than that of the azole drugs. Terbinafine inhibits squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway. Though it is not related to the azole drugs it still is toxic to the liver. Other: Mycelex Troche/ Clotrimazole – is well absorbed by the GI tract, but much of the drug is lost through first-pass metabolism by the liver. And due to its lipophilic nature, the drug would bind to proteins in the blood so that little was available to have its antifungal effect. Also serious side effects – anemia and thrombocytosis (high platelets) – arose for systemic administration. Anti-Parasitic Pharmaceuticals There are numerous anti-parasitic drugs on the market. And each one is used for anyone of the numerous parasites that can make their way into the human gut. Therefore, at this time detailed information is beyond the scope of this report. Further information can be found on-line. Intestinal Dysbiosis: “Natural” Treatments Antifungals in essence are similar to antibiotics in that they are – “against life”. The microorganisms in the gut have been around for millions of years and therefore have learned to morph and adapt. This fact along with the overuse of antibiotics is why there is so much antibiotic resistance. The same phenomenon also takes place with antifungals and fungi… when trying to kill fungi with antifungal medications the fungi will learn to morph, adapt and become resistant. This is what happens when you try to “kill” candida. Natural antifungals on the other hand tend to “inhibit” more than they kill. Some of the more common “natural” remedies for intestinal dysbiosis are discussed below. Probiotics Probiotics is a term used to describe the “friendly” microorganisms most of which can be found as residence in the human gut or transients just passing through. Probiotics can be found in fermented foods or a person can simply take a pill… a supplement. The beneficial properties of probiotics are due to their ability to restore the balance of the normal flora in the human gut/intestine. A number of species and strains of bacteria and yeast have been evaluated for their potential probiotic properties. Below is a list of the microorganism species from which probiotic strains have been isolated and tested in the laboratory or have been used in the production of probiotic supplements and in the processing of foodstuffs. Different probiotic species or even different strains from the same species may exert different effects. Bacterial Probiotics: Lactobacillus species – Lactobacilli have long been the most prominent probiotic microorganism because of their association with popular fermented dairy products. Lactobacilli are part of a large group of lactic-acid producing bacteria. Named as such because most species convert lactose (milk sugar) and other sugars to lactic acid. There are over 125 species of lactobacilli some of which are listed below. L. acidophilus – a natural resident of the human gut, however, properties of adherence and stability in the G.I. tract are strain specific. Several L. acidophilus strains have been shown to: Produce antimicrobial substances in vitro. Produce lactase – enzyme which helps digest lactose. Helps reduce levels of cholesterol. Reduces the proliferation of candida. L. acidophilus DDS-1 Super Strain - there are approximately 200 different strains of L. acidophilus and they are definitely not created equal. Many strains cannot even survive human gut fluid and bile salts. The DDS-1 super strain and the dairy-free NAS super adhesion strain are the ones most highly recommended because they have been shown to: Be the most effective against the widest number of pathogens. Produce extremely effective natural antibiotic substances that can inhibit eleven know disease causing bacteria. Inhibit yeast infections, improve constipation, aid in nutrient uptake and prevent food poisoning. Shows good assimilation of “bad” cholesterol. Note: DDS-1 must be cultured in milk to get its positive properties. L. bulgaricus – is a non-resident/transient bacteria of the human gut. Used in the preparation of yogurt and produce lactase. L. bulgaricus LB-51 Super Strain – this strain is so powerful it is known as the “supreme strain”. LB-51 synthesizes a natural antibiotic substance that has such a wide spectrum of activity. L. brevis – a non-resident/transient bacteria of the human gut. Along with lactic acid L. brevis produces – alcohol (ethanol), acetic acid and carbon dioxide. Found in milk, kefir, cheese and sauerkraut. L. casei – a non-resident/transient bacteria of the human gut. Also found in milk, cheese and dairy products. The probiotic properties of L. casei are strain specific. L. casei strain Shirota has received much commercial attention. It is effective against E. coli and the influenza virus in mice and reduces ulcer causing H. pylori in humans. It survives passage through the intestinal tract. L. delbruecki – a non-resident/transient bacteria of the human gut. L. jugurti (L. yoghurt) – found in sour milk, cheese. L. kefir (formally L. caucasicus) – a non-resident/transient bacteria of the human gut. Along with lactic acid L.kefir produces – alcohol (ethanol), acetic acid and carbon dioxide. Found in kefir grains and kefir milk. L. rhamnosus GG – is the most studied lactobacilli probiotic. It is stable in bile and acid and adheres to intestinal cells in vitro. Also, in vitro a substance produced from this strain kills a relatively broad spectrum of bacteria. (unsure if this takes place in vivo). It has been found to decrease fecal B-glucuronidase-specific activity. And it was also found to inhibit streptococcus sobrinus (involved in dental caries). L. plantarum – a non-resident/transient bacteria of the human gut. Found in dairy products, sauerkraut, pickled vegetables. L. reuteri – in vitro L. reuteri produces several compounds that can destroy a wide variety of harmful bacteria (but unsure if this takes place in vivo). L. salivarius – a natural resident of the human gut. Bifidobacterium species – are major inhabitants of the large intestine (colon). When bifidobacteria are present in sufficient strength, they compete ferociously for both nutrients and attachment sites along the intestinal walls. Another way they protect themselves is by producing both acetic and lactic acids which create a hostile environment (lowers pH) for dangerous microbes that require an alkaline atmosphere. – B. bifidum – inhibit harmful bacteria from converting nitrates to harmful nitrites. Produce B vitamins, levels decline with age/illness. – B. bifidum Malyoth Super Stain – recommended for large intestine therapy, liver detoxification, food/chemical/environmental sensitivities, microbial or fungal over growth, chronic immune suppression, dysbiosis, nutrient malabsorption, B-complex deficiencies, and inflammation of the large intestine. Found in bases of nonfat milk, whey or garbanzo beans extract. – B. longum – a natural resident of the human gut. Bifidobacterium longum is very helpful because it maintains a normal digestive tract, inhibits the growth of harmful bacteria, and also boosts immunity. – Other Bifidobacterium pecies that need further research are: B. infantis, B. breve, B. thermophiles, B. adolescentis, B. catenulatus, B. pseudocatenulatus, B. lactis Streptococcus species – is part of the lactic acid forming bacterial group. S. thermophilus – a non-resident/transient bacteria of the human gut. It is used to make yogurt. S. lactis – a non-resident/transient bacteria of the human gut. Used as a starter for cheddar cheese, cottage cheese. S. cremoris – used in commercial starters for the production of butter, cultured buttermilk and certain cheeses. Enterococcus species – part of the lactic acid forming bacterial group. E. faecalis (formally Streptococcus faecalis) - normally a commensal bacterium which inhabits the G.I. tract. However, E. faecalis can become pathogenic and cause infections in the heart (endocarditis), urinary tract, bladder, and prostate. It is also among the most antibiotic resistant bacteria known. Commonly found in soil, sewage, water, plants and in hospitals. E. faecium (formally Streptococcus faecium) – also produces antibacterial peptides called bacteriocins. This microbe can be used in fermenting foods such as cheese and vegetables. It is introduced to the starting cultures to inhibit growth of unwanted microbes. E. faecium can also be used as a probiotic to out-compete harmful bacteria in the gastrointestinal tract. Lactococcus species – part of the lactic acid forming bacterial group. These bacteria are commonly used in the dairy industry in the manufacture of fermented dairy products like cheese. Their main purpose is the rapid acidification of milk. This causes a drop in the pH which prevents the growth of spoilage bacteria. Leuconostoc species – part of the lactic acid forming bacterial group. Are traditionally found in association with fermenting vegetables, milk, dairy products, and wines. For example it is one of the bacteria responsible for the fermentation of cabbage to make sauerkraut. Pediococcus species – part of the lactic acid forming bacterial group. Along with Leuconostoc and Lactobacilli are responsible for the fermentation of salami, pepperoni, and cabbage into sauerkraut. They are also commonly added as beneficial microbes in the creation of cheeses and yogurt. Propionibacterium species – along with lactic acid, propionibacterium also produce acetic acid and propionic acid. Found all over the body as commensal, and used in making the characteristic holes of Swiss cheese. Bacillus species – it is questionable in having the bacillus species as probiotics. B. subtilis – aerobic spore forming bacteria found in the human intestine in very small amounts. They have been implicated in food poisoning and therefore maybe regarded as undesirable bacteria. B. subtilis is effective against fungus, bacteria, and parasites. It is the basis for one of the most powerful antibiotics (Bacitracin). This product is antibacterial and will act like an antibiotic killing the bad as well as the friendly gut flora. It is also antifungal and my cause resistance. B. sphaericus – aerobic spore forming bacteria found in soil, marine and freshwater sediment, milk and foods. They have been implicated in food poisoning and therefore maybe regarded as undesirable bacteria. B laterosporus – aerobic spore forming bacteria sometimes found in human intestine in very small numbers. B. firmus – aerobic spore forming bacteria which is a non-toxic and non-pathogenic bacterium of external environment. B.firmus was found to have immune-modulatory properties such as: Increase the resistance of mice against experimental infection. Activation of human lymphocytes Macrophage activation in mice Strong stimulatory effect on immunoglobulin synthesis, especially IgA. Fungi Probiotics: Aspergillus species – is a genus in the fungi kingdom that includes several hundred mold species. Are highly aerobic and are found in oxygen rich environments. A. niger – fungus which is a major source of citric acid ( accounts for 99% of global citric acid production) A. oryzae – used in Chinese and Japanese cuisine to ferment soybeans. Also used to ferment rice, grains and potatoes in the making of alcoholic beverages such as sake and rice vinegar. Saccharomyces species – is a genus in the fungi kingdom that includes many species of yeast. S. boulardii (brand name – Florastor) – has been shown to maintain and restore the natural flora in the small and large intestine of humans and is classified as a probiotic. As a probiotic S. boulardii has been shown to improve diarrhea symptoms related to - Irritable Bowel Syndrome, Inflammatory Bowel Disease, Traveler’s diarrhea, Antibiotic-associated diarrhea, and HIV/AIDS. S. boulardii also has other effects such as: o Anti-toxin – degrades toxins released by Clostidium difficile which causes diarrhea. o Anti-microbial – pathogenic bacteria adhere to S. boulardii receptors and are then eliminated in stool. o Anti-inflammatory – reduces IL-8 (pro-inflammatory) and may have a protective effect in IBD. o Increase Immune response – S. boulardii induces secretions of Immunoglobulin A (IgA) in the small intestine. IgA provides protection against invading microbes in the G.I. and respiratory tracts. S. cerevisiae (a.k.a. brewer’s yeast, baker’s yeast) used in making wine, bread, and beer. This species is also the main source for deactivated yeast known as nutritional yeast and yeast extract. S. bayanus – used in making wine and cider. Prebiotic Supplements Are non-digestible food ingredients that stimulate the growth of “friendly” bacteria (probiotics) in the gut, and thereby increase the amount of lactic acid produced in the gut. It is beyond the scope of this report to cover in detail the area of prebiotics. Note: prebiotics have been shown to promote intestinal permeability and irritation of the gut lining. Also, there are hints that prebiotics may also promote the growth of undesirable bacteria as well. Diet Starving candida is impossible… candida can go dormant… candida can get all its nutrients from the body so it doesn’t need to look outside the body for fuel… attempting to starve it will actually cause the yeast to fungal conversion to take place. Then to survive fungal candida will then search out and “go shopping” traveling through the body to find nutrients. No sugars… we can’t starve candida, but on the other hand we don’t want to accelerate candida’s growth either. Sugars feed and cause rapid growth of candida in the body. No sugar substitutes (stevia, etc.). Sugar substitutes can cause the same unwanted effects in the body as sugar because of something called – conditioned reflexes. This is due to a life time of repetitive exposures to sugar and sugar substitutes. No foods that are mucous forming which will coat and protect candida (candida already creates its own biofilm to protect it). No fungi foods (yeast, mold). Mold Load – if candida plays a role in making a person sick, eating or breathing other yeasts and molds may aggravate your symptoms. See fermented foods below. Fermented Foods The information available pertaining to the use of fermented foods to correct an imbalance in a person’s intestinal flora is confusing to say the least. A closer look at this issue indicates that the problem is in the blanket or generalized statements that are made either to eat or not to eat fermented foods. The real answer is that both camps are right when you break down fermented foods into those that are fermented via bacteria and those that are fermented via yeast. As mentioned above, fermentation typically is the conversion of sugars and other carbohydrates to ethanol/alcohol and carbon dioxide or organic acids. More specifically, fermentation can refer to yeast microorganisms converting sugar/carbohydrates to alcohol and carbon dioxide. Or it can refer to bacterial microorganisms converting sugar/carbohydrates to organic acids. When gut dysbiosis exists due to a candida/yeast over growth, a person should avoid yeast fermented foods which can aggravate the situation. This is due to the alcohol and yeast contents of these foods. However, bacterial fermentation may have medicinal effects because of the organic acids (lactic acid, etc.) that are formed. Below is a list of both yeast and bacterial fermented foods and beverages. Yeast Fermented Beverages: Hard Cider (U.S.) – fresh cider is raw apple juice that has not undergone a filtration process to remove coarse particles or pulp or sediment. Fresh cider which is further fermented with a yeast culture to produce alcohol is known as “hard cider” with an alcohol content of 2-8%. “Hard cider” in the U.S. is known simply as “cider” in the rest of the world. Beer – the basic ingredients of beer consist of water; a starch source such as rice, wheat, corn and malted barley; a brewer’s yeast such as Saccharomyces cerevisiae or Saccharomyces pastorianus; and a flavoring such as hops. Yeast metabolizes or ferments the sugars from grains into carbon dioxide and alcohol. The alcohol content of beers ranges from 3.5% to as high as 10%. Wine – is an alcoholic beverage made of fermented fruit juice, usually from grapes. Grape wine is produced by fermenting crushed grapes, with their natural sugars, and the use of a variety of different yeast. Different varieties of grapes and strains of yeasts produce different types of wine. The alcohol content of wine ranges from 8 to 20%. Hard Liquor/Distilled Liquor – the process of fermentation on grains and other starches by yeast naturally stops when the alcohol content reaches about 20%. However, through the process of distillation higher concentrations of alcohol can be achieved to create products such as whiskey, vodka, tequila, gin, rum, etc. These products contain alcohol contents between 20 – 70%. Brandy – comes from the same distilling process as hard liquor except the original sugar/starch source comes from grapes rather than grains. Alcohol content – 35 – 60% Yeast Fermented Foods: Bread (leavened only) – the basic ingredients of bread consist of dough (paste of any cereal grains), water, salt, fat, and a leavening agent. Leavening agent such as baking soda or baker’s yeast (Saccharomyces cerevisiae) which produce alcohol and carbon dioxide byproducts. The carbon dioxide is a gas used to create bubbles and raise the bread. The alcohol is destroyed during baking. Miso – is a traditional Japanese seasoning produced by fermenting a variety of grains and/or soybeans with salt and the fungus Aspergillus oryzae (mold culture), and then aged in vats. The result is a thick paste used more commonly in the making of miso soup. However, because of its strong flavor it is added to sauces, spreads, salad dressings, marinades, vegetable dishes and in the pickling of vegetables (cucumber, daikon, eggplant). The wide variety of miso is difficult to classify but is commonly done by grain type. Soy/Soya Sauce – is a condiment produced by fermenting soybeans along with a grain (usually wheat), salt, water and the fungus or koji mold – Aspergillus oryzae or Aspergillus soyae. The naturally brewed style of soy sauce contains 1-2% alcohol. Other types of soy sauce made from hydrolyzed soy protein and corn syrup do not produce alcohol, but alcohol maybe added during bottling as a preservative. Tamari – same as soy sauce except it is usually made without wheat. Tempeh – is a traditional soy product originally from Indonesia. It is made with the fungus – Rhizopus oligosporus via a fermentation process that binds soybeans into a cake form. The beans are knitted together by a mat of white mycelia (mass branching of hyphae threads/roots). Bacterial Fermented Foods: Kimchi – is a traditional fermented Korean dish made from vegetables and a variety of seasonings. The typical bacterial species used for the fermentation process is the lactic acid bacteria Lactobacillus kimchi. Natto – is a traditional Japanese food made from soybeans fermented with the bacteria Bacillus natto which is a strain of Bacillus subtilis. Natto possesses an odor of ammonia caused by the fermentation of the amino acids by Bacillus subtilis natto. During the natto fermentation viscous and sticky polymers (polyglutamic acid) are produced which makes the natto very slimy. Salami and Pepperoni – a choice of ground up meat (usually pork or beef) salt, nitrate, sugar and a culture starter are mixed up and stuffed into a casing. Once in the casing the meat begins to cure and ferment. Over time it will also dry and will then be ready to eat. The most common culture starters used are Lactobacillus plantarum and various Pediococcus species which are used to produce lactic acid and create an unfriendly environment for possible pathogenic bacteria. Cheese – is a generic term for a diverse group of milk-based food products. Cheese making begins by adding a starter culture/bacteria to milk, which causes the milk to acidify or sour. This also causes the milk to form solid curds and liquid whey. At this stage the two byproducts are separated with the solid curds being processed through several more steps to become the final cheese product. Most cheeses are made with starter cultures/bacteria from the Lactococci, Lactobacilli or Streptococci families. Then during the ripening/aging process other, mainly lactic acid bacteria which arrived via the milk spontaneously grow. Buttermilk – refers to a number of dairy drinks one of which may be a fermented product with a characteristically sour taste caused by lactic acid bacteria. This variant is made in one of two ways (1) “cultured” buttermilk with Streptococcus lactis or (2) “Bulgarian” buttermilk with Lactobacillus bulgaricus (more tartness). Sour Cream – is a dairy product rich in fats obtained by fermenting cream (butterfat/milk fat portion of milk) with certain lactic acid bacteria. The bacterial culture sours and thickens the cream. Yogurt – is a dairy product produced by bacterial fermentation of milk. The bacterial cultures most often used are – Lactobacillus bulgaricus, and Streptococcus thermophiles. Also added sometimes are Lactobacillus acidophilus, Lactobacillus bifidus and Lactobacillus casei. When these bacteria are added to milk and allowed to ferment, the resulting culture is a naturally sweet, mildly tangy, smooth, fresh-tasting custard-like treat. And thanks to the action of the bacteria, true yogurt is almost a predigested food. Within an hour after eating yogurt, 90% of it is digested. Fruit that is added to most commercial yogurt is processed, not fresh. Plus the live bacteria used as a culturing agent would rather nibble on the fruit sugars than ferment the milk. Also where the fruit is layered on the top or the bottom, or swirled through the yogurt, chemical additives are placed between the fruit and the cultured milk to keep the live bacteria from coming into contact with the fruit. Yeast and Fermented Foods & Beverages: Kefir – is a fermented milk drink which is prepared by inoculating cow, goat or sheep’s milk with “kefir grains”. Kefir grains are a combination of both bacteria and yeast in a matrix of proteins, lipids and sugars. Many different bacteria and yeasts are found in the kefir grains, which are a complex and variable community of lactic acid bacteria and yeasts. The yeast produces a small amount of alcohol - 1%. Kombucha – is a fermented tea drink. Kombucha is made with water, sugar, brewed tea (usually black or green) and a kombucha culture. The kombucha culture is a symbiosis of both Acetobacter xylinum (acetic acid bacteria) and one or more yeast such as Saccharomyces cervisiae, Brettanomyces bruxellensis, Candida stellate, etc. First the yeast will produce alcohol at which point the bacteria will then convert the alcohol to acetic acid. Not all the alcohol is converted in the fermentation process leaving a alcohol content of ½% to 1%. Pickled Vegetables (Pickling) – is the process of preserving food via the fermentation process which takes place in a brine/salt water solution to produce lactic acid. This process produces an environment where the pH is less than 4.6 which is sufficient to kill most bacteria (except lactic acid producing bacteria). It is important to note that the fermentation process that takes place during pickling is a “natural” fermentation process. Meaning no yeast or bacterial cultures is added. The fermentation takes place from the bacteria and yeast that is naturally found on the foods being pickled. Though antimicrobial herbs such as mustard seed, garlic, cinnamon, or cloves are sometimes added. The list of pickled foods is long, but some of the more common pickled foods are: cucumbers, olives, sauerkraut, tomatoes, eggs, pig’s feet, etc. Sake/Rice Wine - is a rice based Japanese alcoholic beverage with an alcohol content of 15 – 20%. Unlike beer, sake goes through a multiple fermentation process first by koji mold (Aspergillus oryzae), a second yeast and then a lactic acid bacterial fermentation. Sour Dough Bread - Sourdough bread is a dough which also contains the bacteria lactobacillus which produces lactic acid giving bread a sour taste. Vinegar – is an acidic liquid produced from the fermentation of ethanol/alcohol into acetic acid. Vinegar production takes place in a two stage fermentation process. The first stage occurs when yeast change natural sugars to alcohol (alcohol fermentation). In the second stage a group of Acetobacter (acetic acid bacteria) further ferments the alcohol into acetic acid. Used as a condiment the acetic acid concentration typically ranges from 4-8%. The ethanol may be derived from many different sources including wine, beer, cider, etc. or it may be made synthetically from natural gas and petroleum derivatives. As a result of having numerous sources you have a wide variety of vinegars. Fatty Acids Most organic fatty acids are fungicidal and have been used for centuries as antimicrobial agents, originally in the manufacture of soaps. Although the fungistatic and fungicidal effects of fatty acids have been well documented, they can be somewhat irritating to mucous membranes in certain people, and commonly used fatty acids such as caprylic and undecylenic acids have an objectionable taste and odor. Undecylenic Acid (10-undecenoic acid) – a substance found naturally in the body (occurring in sweat). It causes fungal candida to revert back to its yeast form in a slightly weekend state. At this point the immune system – specifically neutrophils will hopefully take over and attack the yeast. Extracted from castor bean oil undecylenic acid is reported to be up to 6 times as potent as caprylic acid. Thorne Research who manufacture the undercylenic acid nutritional supplement Formula SF 722 state that its molecular structure makes undecylenic acid the most potent antifungal of all the fatty acids. Caprylic Acid – in a pH range of 2.5 - 8.5 caprylic acid exhibits high fungicidal activity against yeasts, especially Candida albicans. The exact mechanism of fungicidal action of caprylic acid is not fully understood, however, it is postulated that caprylic acid dissolves the cell membrane of yeast, causing changes in fluidity and permeability that lead to membrane destruction. However, caprylic acid has liver and kidney toxicity associated with it. Due to its toxicity it is limited for use up to 4-5 weeks which is not long enough to get rid of systemic yeast while during this time toxicity in the kidney is taking place. Extracted from coconut oil. Lauric Acid – the body converts lauric acid into monolaurin. Monolaurin’s has anti-viral and anti-bacterial properties. Lauric acid is also extracted from coconut oil Herbal Remedies The list of herbal remedies which claim to be effective against fungi is long with varying degrees of effectiveness. Further research is needed to detail each herb’s effectiveness, which at this time is beyond the scope of this report. However, some of the more common antifungal herbs are listed below. Barberry - has antifungal properties useful in killing yeast cells. Black Walnut – antifungal, antiparasitic Calendula –antifungal, antibacterial, antiinflammatory, liver tonic Cinnamon – a decoction is held in the mouth for treating thrush Garlic - has antifungal properties and can be used liberally in food preparation or taken as capsules. Lemon Grass – has antibacterial and antifungal properties and it can repair damaged intestinal walls. Olive Leaf - powerful antimicrobial. Capsules or tinctures are taken internally. Oregano Oil - has powerful antifungal properties. Pau d’arco – antifungal properties, boost immune system Peppermint – antifungal, used as an infusion. Oil is available in capsules. Rosemary - has antifungal properties useful in killing yeast cells. Tee Tree Oil – antifungal, used to treat thrush (mouthwash). Do not swallow! Thyme Oil - is an antifungal which can be diluted and used topically. Note: caution needs to be taken with herbs because yeast and molds will tend to grow on them, which in some cases will aggravate the conditions when taken. Vitamins and Minerals Biotin - is a B-complex vitamin and plays a very important role in preventing candida from turning into its rampantly aggressive mycelia or fungal form in which it puts down roots (rhizomes) and spreads rapidly. Biotin, taken in an amount of at least 3mg will stop the transformation cycle from the yeast to the fungus form. Molybdenum – a trace mineral needed by the enzyme aldehyde dehydrogenase to convert toxic acetaldehyde (candida byproduct) into acetyl-CoA which has several important functions in the body. Other Hydrochloric Acid (HCL) – supplemental HCL will be needed in cases of hypochlorhydria. Grapefruit Seed Extract – antifungal, antibiotic Propolis – created by bees has antifungal properties Fiber One of the pillars in the successful therapy of candida is the maintaining of a regular bowel movement. Consuming fiber reduces transit time and results in a more thorough evacuation of waste materials. It is thought to improve all aspects of colon function. Constipation is almost always present in the case of candida, inducing die-off symptoms. One should consume 30-40 grams of dietary fiber per day. It is important to get a balanced amount of both soluble and insoluble fiber. Soluble fiber - soluble fiber dissolves in water and it forms a bulky gel in the intestine that regulates the flow of waste materials through the digestive tract. Found in- oatmeal, oat bran, rice bran, legumes, beans, psyllium, flax seed, nuts, fruit pectin – apples, apricot, plums, cherries, oranges and other citrus fruit. Insoluble fiber - cannot be dissolved in water, meaning that our bodies cannot digest it. The primary function of insoluble fiber is to collect water that increases stool bulk in the large intestine. This promotes bowel movement, and as the bulk works through the intestine, it scours the intestinal walls of waste matter, reducing the risk of colon-related problems. Found in – in the stringy un-dissolvable parts of plant walls and is found in greatest amounts in plant leaves (greens), peels (cabbage, beets, Brussels sprouts, turnips, cauliflower), skins (apple) and the coverings of whole grains (wheat, rye, rice, barely, corn, etc). Both types of fiber bind with bile (contains toxins) and the body’s waste products to help move them through the intestine, but it is soluble fiber which is doing the bulk of the work. Oxygen Based Products Because most of the bacterium in the gut/intestines are anaerobic introducing oxygen into the gut/intestines via oxygen based products, will disrupt the entire gut micro flora. Even then you still won’t kill the yeast because candida is a – facultative anaerobic organism. A facultative anaerobic organism is an organism that can live in the absence as well as in the presence of oxygen. Candida can adapt and can therefor live in an oxygen deprived environment like the gut or it can live in an oxygen rich environment like the blood (systemic). Mercury Amalgam Removal This is a very controversial topic. Many claim that mercury “feeds” candida. However, the scientific literature shows this to be a myth and not true. What mercury does is suppress the immune system which can then facilitate the growth of candida. Also, candida has the ability to convert inorganic mercury (amalgams) to methyl mercury which is much more toxic to tissue (especially brain) and is the form that can cross the blood brain barrier. Healing Crisis/Herxheimer Reaction/Die-Off During the process of using the various methods mentioned above to rid the gut of pathogenic microorganisms, a healing crisis or a Herxheimer/die-off reaction may take place. This occurs when large quantities of pathogenic microorganisms are killed, thereby releasing toxins into the body. If the body is unable to remove and detoxify the toxins faster than they are released into the body various symptoms will occur. It is the occurrence of these symptoms that makes a person feel sick and is said to be experiencing a “healing crisis” or a Herxheimer/die-off reaction. The symptoms associated with a healing crisis or Herxheimer/die-off reactions are in general flu like symptoms such as: Headache Joint & muscle pain Body aches Fever and chills Nausea Brain fog Sore throat Digestive disturbances Fatigue Cytokine Storm Interestingly, some doctors/researchers feel that during microorganism elimination treatments, that the “flu like” symptoms they experience are due to something termed a “cytokine storm” rather than a Herxheimer reaction. These treatments cause the immune system to respond and release cytokines which create a pro-inflammatory response. Sweating Die off – is when the tissues become overwhelmed with the toxins which in turn creates a lot of inflammation and mucus (which will coat the candida) which interferes with the elimination of yeast byproducts. Therefore, a person must sweat the toxins out via sweating – saunas or hot baths. The heat has to come from the outside, not the inside; therefore sweating from exercise does not work. Sweating will also reduce die-off symptoms. References Books: Chaitow L., Trenev N., Probiotics: The Revolutionary Friendly Bacteria Way to Vital Health and Well-Being, Thorson Publishing Group (1990) Crook W.G., The Yeast Connection: A Medical Breakthrough, Professional Books (1994) Elmer G. W., McFarland L.V., McFarland M., The Power of Probiotics – Improving Your Health with Beneficial Microbes, The Hawthorne Press (2007) Fuller R., Perdigon G., Gut Flora, Nutrition, Immunity and Health, Wiley-Blackwell (2003) Murray M.T., Chronic Candidiasis – The Yeast Syndrome, Prima Publishing (1997) Schepper L.D., Candida, [self-published], (1986) Trenev N., Probiotics: Natures Internal Healers, Avery Publishing Group (1998) Trowbridge J.P., Walker M., The Yeast Syndrome, Bantam Books (1986) Truss O.C., The Missing Diagnosis II, [self-published], (2009) Watson R.R., Bioactive Foods in Promoting Health: Probiotics and Prebiotics, Elsevier Inc. (2010) Journal Publications: Connolly E., Lonnerdal B., D-Lactic Acid-Producing Bacteria: Safe to use in infant formulas, Nutrafoods, 3(3): 37-49 (2004) Dismukes W.E., Introduction to Antifungal Drugs, Clinical Infectious Diseases, 30: 653-657 (2000) Dix Lemle M., Hypothesis: Chronic Fatigue Syndrome is caused by Dysregulation of Hydrogen Sulfide Metabolism, Medical Hypotheses (2008) Gibson G.R., MacFarlane G.T., Cummings J.H., Sulphate Reducing Bacteria and Hydrogen Metabolism in the Human Large Intestine, Gut, 34: 437-439 (1993) Hughes R., Magee E.A.M., Bingham S., Protein Degradation in the Large Intestine: Relevance of Colorectal Cancer, Current Issues in Molecular Biology, 1(2): 51-58 (2000) Loubinoux J., Bronowicki JP., Pereira I., Mougenel JL., Sulfate reducing bacteria in human feces and their association with inflammatory bowel disease, FEMS Microbiology Ecology, 40(2): 107-112 (2002) Malloy P.J., Zhao X., Madani N.D., Feldman D., Cloning and expression of the gene from Candida albicans that encodes a high-affinity corticosteroid-binding protein, Proceedings of the National Academy of Science, 90:1902-1906 (1993) Prokesova L., Mlckova P., Stankova I., Chloubova A., Novotna V., Ladmanova P., Chalupna P., Mara M., Effect of Bacillus firmus on Antibody Formation after Mucosal and Parenteral Immunization in Mice, Immunology Letter, 64: 161-166 (1998) Sanders M.E., Morielli L., Tompkins T.A., Sporeformers as Human Probiotics: Bacillus, Sporolactobacillus, and Brevibacillus, Comprehensive Reviews in Food Science and Food Safety, 2: 101-110 (2003) Sheedy J.R., Wettehhall R.E.H., Scanlon D., Gooley P.R., Lewis D.P., McGregor N., Stapleton D.I., Butt H.L., and DeMeirleir K.L., Increased D-Lactic Acid Intestinal Bacteria in Patients with Chronic Fatigue Syndrome, in vivo,23: 621-628 (2009) Summerskill W.H.J., Wolpert E., Ammonia Metabolism in the Gut, The American Journal of Clinical Nutrition, 23(5): 633-639 (1970) Ten Bruggencate S.J.M., Bovee-Oudenhoven M.J., Lettink-Wissink M.L.G., Dietary Fructooligosaccharides Increase Intestinal Permeability in Rats, Nutritional Immunology, 135: 837-842 (2005) Truss C.O., Metabolic Abnormalities in Patients with Chronic Candidiasis, Journal of Orthomolecular Psychiatry, 13(2): 66-93 (1984) World Wide Web: Breakspear Medical Bulletin, 2010 Dr. Z’s site Dr. Joseph Mercola’s site Dr. Jeffrey McComb’s site Dr. Leo Galland’s site Dr. Alan Logan’s site NPR – The Human Gut is a Real Melting Pot, Nov 21, 2008 Pub Med Health Pro Health – Immune Support Wikipedia