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Dr. Jehan Abdul Sattar Probiotics BENEFICIAL EFFECTS OF PROBIOTICS In the last 40 years, studies have been conducted to determine specific health benefits from the consumption of live cells of beneficial bacteria. Live cells have been consumed from three principal sources: (1) as fermented milk products, such as yogurt, which contains live cells of Lb. delbrueckii ssp. bulgaricus and S. thermophilus and is supplemented with Lb. acidophilus and others, and pasteurized milk, which contains Lb. acidophilus; (2) as supplementation of foods and drinks with live cells of one, two, or more types of beneficial intestinal bacteria, such as Lb. acidophilus, Lb. reuteri, Lb. casei, and Bifidobacterium species; and (3) as pharmaceutical products of live cells in the form of tablets, capsules, and granules. The beneficial effects from consuming these live cells were attributed to their ability to provide protection against enteric pathogens, supply enzymes to help metabolize some food nutrients (such as lactase to hydrolyze lactose) and detoxify some harmful food components and metabolites in the intestine, stimulate intestinal immune systems, and improve intestinal peristaltic activity. *Lactose Hydrolysis People who lack the ability to digest lactose adequately are classified as lactose maldigestors. (In the past, terms such as ‘‘lactose intolerance’’ or ‘‘lactose malabsorption’’have been used to describe this condition). Lactose-intolerant individuals, because of a genetic disorder, are unable to produce lactase (β-galactosidase) in the small intestine. When they consume milk, lactose molecules are not hydrolyzed in or absorbed from the small intestine but passed to the colon. They are then hydrolyzed in the colon by lactase of different bacteria to glucose and galactose and then further 1 metabolized to produce acids and gas, resulting in fluid accumulation, diarrhea, and flatulence. Consumption of yogurt, acidophilus milk, live cells of Lactobacillus, especially Lb. acidophilus in fresh milk and pharmaceutical products, reduces the symptoms in lactose-intolerant individuals. This benefit is attributed to the ability of beneficial bacteria to supply the needed lactase in the small intestine. However, as Lb. delbrueckii ssp. bulgaricus and S.thermophilus do not survive stomach acidity well and are not normal intestinal bacteria, the benefit of consuming normal yogurt due to the reduced amounts of lactose in yogurt, as compared to milk, and to the supply of lactase from the dead cells. The presence of viable starter cultures in yogurt can be beneficial to lactose maldigestors . This beneficial action results from presence of β-galactosidase in the bacterial cells. Apparently being inside the bacterial cells protects the enzyme during passage through the stomach so that it is present and active when yogurt reaches the small intestine. In contrast, the intestinal bacteria, especially some Lactobacillus species, could, under proper conditions, colonize the small intestine and subsequently supply lactase. Once the yogurt culture reaches the small intestine,it interacts with bile, which increases permeability of the cells of these bacteria and enables the substrate to enter and be hydrolyzed. The enzyme remains inside the cell upon exposure to bile rather than leaking out into the surrounding medium. As mentioned previously, the starter cultures used for yogurt manufacture (Lb. delbrueckii subsp. bulgaricus and S. thermophilus) are not bile resistant and thus are not expected to survive and grow in the intestinal tract. Despite this limitation, consumption of these bacteria provides a means of transferring β-galactosidase into the small intestine where it can improve lactose utilization in lactose maldigestors. Nonfermented milk containing cells of Lb. acidophilus also can be beneficial for lactose maldigestors . This organism, unlike the yogurt starter cultures, can survive and grow in the intestinal tract. However, a similar mechanism in improving lactose utilization in lactose maldigestors to that observed for yogurt 2 bacteria is probably involved. β-Galactosidase activity of cells of Lb. acidophilus is greatly increased in the presence of bile because of increased cellular permeability. As with yogurt cultures, cells of Lb. acidophilus do not lyse in the presence of bile, but their permeability is increased permitting lactose to enter the cells and be hydrolyzed. Because Lb. acidophilus can survive and grow in the intestinal tract, it is reasonable to expect, however, that additional β-galactosidase may be formed after ingestion of milk containing this organism. The ability of probiotic enzymes to aid digestion has also been studied in infants with sucrase deficiency. The ability to digest sucrose was augmented by the ingestion of Saccharomyces cerevisiae, a yeast that produces the sucrase enzyme. * Reducing Serum Cholesterol Level Consumption of fermented dairy product and high numbers of live cells of beneficial intestinal bacteria has been associated with low levels of serum cholesterol in humans. This is attributed to two possible factors. One is the ability of some intestinal lactobacilli to metabolize dietary cholesterol, thereby reducing amounts absorbed in blood. The other possibility is that some lactobacilli can deconjugate bile salts and prevent their reabsorption in the liver. The liver, in turn, uses more serum cholesterol to synthesize bile salts and indirectly helps reduce cholesterol level in serum. There are many of probiotic organisms that can help to control serum cholesterol levels. Some of these include Lb. casei , Lb. acidophilus and Bifidobacterium species . * Reducing Colon Cancer Many of the undesirable bacteria in the colon have enzymes that can activate procarcinogens, either present in food or produced through metabolism of undesirable bacteria, to active carcinogens that, in turn, can cause colon cancer. Beneficial intestinal bacteria, both Lactobacillus and Bifidobacterium species, by their ability to control growth of undesirable bacteria in the colon, can reduce the production of these enzymes. Also, 3 beneficial bacteria, by increasing intestinal peristaltic activity, aid in regular removal of fecal materials. This, in turn, lowers the concentrations of the enzymes and carcinogens in the colon and reduces the incidence of colon cancer. Several studies have shown that oral consumption of large numbers of live cells of the beneficial bacteria reduces fecal concentrations of enzymes such as β-glucuronidase, azoreductase, and nitroreductase of undesirable colon bacteria. However, the relationship between reduction of these enzymes and reduction in colon cancer from the consumption of beneficial intestinal bacteria has not been studied, and thus contributions of these bacteria in controlling colon cancer are not clearly known. Lb. acidophilus, Lb. casei, and Lb. delbrueckii subsp. bulgaricus are species most often mentioned as having potential to provide anticarcinogenic actions. For Lb. delbrueckii subsp. bulgaricus, the anticarcinogenic action is associated with substances produced by the organism during manufacture of yogurt as opposed to being produced in the body following consumption of yogurt. However, for Lb.acidophilus and Lb. casei growth or action in the gastrointestinal tract seems to be important. Part of the benefit may involve direct effects in inhibiting tumor formation. However, the main effect may result indirectly through inhibiting growth of undesirable bacteria that form carcinogens in the large intestine. * Modulating Immune Response Enhancement of the body’s immune response by consuming cells of certain lactobacilli increases resistance of the host to intestinal infections . Of the lactobacilli, Lb. casei seems to be the primary one involved . B. longum also can stimulate the immune system to control E.coli in the gastrointestinal tract. Researchers in this area have suggested that this action involves activation of macrophages which in turn destroy pathogenic organisms in the body. It also has been suggested that consumption of these organisms is followed by secretion of components into the intestinal tract which are inhibitory toward 4 certain of the foodborne pathogens. This enhancement of the immune system increases the host defense mechanisms and could be very important for control of foodborne illnesses. This may be a key explanation as to how certain probiotic microorganisms used as dietary adjuncts can exert control over intestinal infections. * Reducing Allergic Diseases Probiotics containing beneficial bacteria can have a suppressive effect by stimulating the production of anti-inflammatory cytokines and reducing allergic reaction in sensitive individuals. Probiotics Lb. rhamnosus GG appears able to reduce atopic disease, not only in infants receiving the probiotic directly, but also where the mother was given the bacterium. Some studies have suggested that an increase in IL-10 in the serum of infant receiving Lb. rhamnosus GG may be responsible for the probiotic effect. Further evidence has suggested that probiotics not only reduce symptoms of atopic disease, but that they can also prevent such conditions from occurring when given prenatally to mothers. * Reducing Bacterial vaginosis and UTI The vaginal micro flora of healthy human females typically comprises about 50 bacterial species. This micro biota is mainly comprised of lactobacilli, which are known to protect the host from colonization by pathogens. In health, epithelial cells lining the vagina are covered with a biofilm in which lactobacilli predominate, and most pathogens are unable to colonize the biofilm. However, breakdown of the biofilm is known to occur in BV, although the ecological and physiological mechanisms involved are unclear. Probiotics are increasingly being regarded to be of therapeutic benefit in BV, partly because of the large numbers of lactobacilli in the healthy vaginal microflora and also because their loss is implicated in disease pathogenesis. 5 Studies on urogenital tract infections, characterized by decreases in the protective lactobacilli genera, revealed that inserted capsules or oral dosages of a probiotic combination, containing Lb. rhamnosus GR and Lb. fermentum RC-14, restored the vaginal flora to a healthy composition in 90% of the women treated. However, several trials using lyophilised Lb. acidophilus applied locally or Lb. acidophilus yoghurt given orally has generated similar results. Other studies have investigated the therapeutic benefits of Lb. rhamnosus GR-1 and Lactobacillus fermentum RC-14 given orally. In vitro experiments suggested that these bacteria possessed several properties, such as adhesion to epithelial cells and production of antimicrobial substances, that could be of clinical value . Further work has suggested that a dose of at least 108 cfu / d of Lb. rhamnosus GR-1 and Lb. fermentum RC-14 is needed for a therapeutic effect . It is therefore likely that any probiotic therapy capable of reducing or preventing BV will also have a beneficial effect on UTI. Indeed, vaginal administration of two capsules per week containing 109 cfu Lb. rhamnosus and Lb. fermentum was found to reduce the UTI recurrence rate to that expected with antibiotic therapy . Reducing Intestinal Disorders Under certain conditions, indicated before, the intestinal population of beneficial bacteria can be reduced. The undesirable bacteria in the intestine and some transient pathogens (such as enteric pathogenic bacteria and Rotoviruses) from the environment can then cause enteric disorders, including infection. Infection results from the invasion and growth of enteric pathogens in the intestine. Ingestion of large numbers of live cells of beneficial intestinal bacteria over a period of time was reported to reduce these problems. Both infants and adults on oral antibiotic therapy can develop diarrhea because of a loss of desirable bacteria in the intestine and an increase in undesirable pathogenic bacteria and viruses. It was suggested that beneficial bacteria, when consumed in large numbers, establish in the intestine and produce 6 antibacterial compounds (acids, bacteriocins, reuterine, and others unknown), which, in turn, control the pathogens. Deconjugation of biles by beneficial species also produces compounds that are more antibacterial than the bile salts; this has also been suggested as a mechanism to control the growth of undesirable enteric bacteria. Probiotic bacteria also increase the specific immunoglobulins, reduce intestinal permeability, and normalize intestinal microflora. -Probiotics in Clostridium difficile-associated intestinal disease Clostridium difficile is a pathogenic bacterium that takes advantage of the compromised GI tract in ~20 to 40% of patients suffering from antibiotic-associated diarrhoea. Intervention with Saccharomyces boulardii in a placebocontrolled trial has shown that the use of this probiotic as an adjunct to the antibiotic therapy prevented relapse . Furthermore, a recent study has shown that probiotic intake reduced the incidence of C. difficile toxin-positive patients as compared to the placebo group .Also Lactobacillus GG was successfully used to treat patients with recurrent diarrhoea caused by C. difficile . -Probiotics in Antibiotic-associated diarrhoea The use of antibiotics to treat infection has devastating consequences on gastrointestinal balance (and particularly upon beneficial bacteria) that can result in diarrhoea in up to 20% of patients receiving antimicrobial therapy. Several well-designed, placebo-controlled randomized trials have demonstrated that S. boulardii, Lactobacillus rhamnosus GG and Enterococcus faecium SF68 were effective at reducing the incidence of diarrhoea in this patient population. Evidently, antibiotic therapy disrupts the intestinal microbiota; however, it is unclear how these probiotics mediate their protection. It is conceivable that they may prevent the growth of pathogens such as C. difficile, or fortify the epithelial barrier. 7 -Probiotics in Acute diarrhoea and gastroenteritis Acute diarrhoea can be caused by rotavirus infection, which is a serious contributor to infant morbidity and mortality, especially in developing countries. Several studies have been conducted with reports of decreases in the incidence and duration of diarrhoea by a decrease in the shedding of rotavirus, following probiotic ingestion of strains such as Lb.rhamnosus GG, Bifidobacterium bifidum and Streptococcus thermophilus . Probiotics need to be viable to exert inhibitory effects. This is because competitive mechanisms such as acid formation, antimicrobial excretion, substrate limitation and occupation of colonization sites all require viability. Also Campylobacter jejuni ( C. jejuni) is an important cause of bacterial-induced enterocolitis in humans in the developed world, caused by consuming infected food. Multiple studies have shown that Lactobacillus, administered orally, may have antidiarrhoeal properties. The ability of lactobacilli to inhibit C. jejuni invasion. Also the effect of the yeast Saccharomyces boulardii on acute diarrhoea was described by shortening the duration of diarrhea. -Probiotics in Constipation and Bloating Constipation is a common heterogeneous gastrointestinal disease affecting up to 27% of the western population. Although there is evidence supporting the fact that probiotics modify the intestinal function. The effect of a probiotics in 266 females with functional constipation, randomized to receive either a mixture of Bifidobacterium animalis and prebiotic fructooligosaccharide (FOS) twice a day for 2 weeks. The results show a 22% increase in the number of bowel movements per week and a slight increase in stool quality when compared to placebo. *Other health benefits: Many other health benefits of probiotics have been claimed, such as increased calcium absorption from the intestine, stimulation of endocrine systems, growth promotion, 8 prolongation of youth and life, production of vitamins(folate ,vitamin B12,vitamin K2, riboflavin and thiamine) has been claimed among the causal relationships of the healthy benefits of probiotics and production of Exopolysaccharide(EPS) have been reported to exert a number of beneficial health effects, including prebiotic , immunomodulating , anti-tumoral,antiulcer and cholesterol-lowering effects . The nasopharyngeal microbiota of children suffering from recurrent otitis media has also been alleviated through the application of a nasal spray containing probiotic microorganisms. 9