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Romanian Biotechnological Letters
Copyright © 2015 University of Bucharest
Vol. 20, No. 1, 2015
Printed in Romania. All rights reserved
ORIGINAL PAPER
Probiotics and therapeutic effect in clinical practice – Review
Received for publication, September 10, 2014
Accepted, November 23, 2014
NICOLETA MAFTEI ARON1, MONICA (GĂUREANU) BOEV2,
GABRIELA BAHRIM2*
1
Department of Pharmaceutical Sciences, Faculty of Medicine and
Pharmacy, “Dunarea de Jos” University of Galati, 35 A.I. Cuza Street,
800010, Galati, Romania
2
Department of Food Science, Food Engineering and Applied
Biotechnology, Faculty of Food Science and Engineering “Dunarea de
Jos” University of Galati, Street: Domneasca No. 111, 800201, Galati,
Romania
*Corresponding author: [email protected]
Abstract
A review regarding the relationships between probiotics and the health is presented. After a brief
historical introduction, the main mechanisms and beneficial effects of probiotics, the immune system,
probiotics like microorganisms and beneficial effects of probiotics on health are presented. Clinical
studies with probiotics are discussed in detail. Many experimental studies have found that probiotics
are specific effects for all diseases studied and discussed in this review. This review underlines the
potential interest in probiotics for the management of diseases pathology.
Keywords: probiotics, mechanism, health, diseases
1. Introduction
The meaning of the term “probiotic” is “for life.” In analogy to antibiotics, “probiotic”
is a general term for different species and strains with a diverse range of clinical and
immunological capacities. The Food and Agriculture Organization (FAO)/World Health
Organization (WHO) defined the probiotics as “live microorganisms which, when administered
in adequate amounts, confer a health benefit on the host,” and launched guidelines regarding
the evaluation of probiotics. The most commonly used probiotics are lactobacilli and
bifidobacteria, but other microorganisms have been used as probiotics including the yeast
Saccharomyces boulardii. Some examples of bacteria used in probiotics formulations are
Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Lactobacillus
salivarius, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus sporogenes,
Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis, Streptococcus
thermophilus and Homeostatic Soil Organisms (HSO’s) [1]. A good probiotic must possess
the following requirements: 1) being able to adhere to cells; 2) excluding or reducing
pathogenic adherence; 3) being able to persist, multiply and produce acids, hydrogen peroxide
and bacteriocins antagonistic to pathogen growth; 4) being able to be safe, noninvasive,
noncarcinogenic and non-pathogenic; 5) being able to co-aggregate in order to form a normal
balanced microbiota [2].
Prebiotics are nondigestible, fermentable food ingredients that selectively stimulate the
growth and the activity of beneficial bacteria in the colon. The combination of prebiotics and
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probiotics is termed as synbiotics. In this combination, the prebiotic substrate may promote
the growth of both the probiotic and other “beneficial” endogenous species [3].
Some of the potential benefits of probiotics include prevention of constipation, colon
cancer, lactose intolerance, infantile diarrhea, travellers’ diarrhea, antibiotic induced diarrhea,
hypercholesterolemia, vaginitis and intestinal infections [4, 5].
For an adequate amount of health benefits, a dose of 5 billion colony forming units
(CFU) has been recommended for at least 5 days (5·109 CFU/day) [6]. Lactobacilli,
bifidobacteria, and lactococci are all included in the category of organisms that are “generally
regarded as safe (GRAS)”, a category in which the spore-forming bacteria, enterococci,
streptococci and Bacillus spp. are not included. Different probiotics have been administered to
a considerable number of individuals under controlled conditions, both infants and adults,
suffering from different conditions, and have been proven to be without associated risks. In
some of these trials, combinations of probiotics have been used. Furthermore, all kinds’ of
products containing these bacteria are sold over the counter and without control to large
segments of population without any undesirable affects [7]. However, concerns persist as
cases of sepsis are reported periodically in the medical literature [8].
The objectives of this review are as follows: 1) different issues of probiotics especially in
reference to pharmaceutical aspects, 2) mechanism of action 3) beneficial effects of probiotics
on health.
2. Proposed mechanisms of beneficial effects of probiotics
In recent years enormous efforts have been made to unravel the mechanisms of probiotic
actions and various experimental approaches have been used for characterizing the molecular
basis of probiotic effects [9]. The mechanisms of beneficial effects of probiotics on human
body have been proposed to be mediated via a number of pathways. Several probiotic strains
antagonize enteropathogens and the mechanisms (although not fully determined yet) may
involve competition for receptor sites and nutrients, aggregation with bacterial pathogens and
production of hydrogen peroxide, presence of antimicrobial substances and stimulation of the
immune system [10, 11]. Prescott and Björkstén (2007) [12] reported that probiotics may
have effects on gut microbial composition, either directly or by effects on microbial products,
host products or food components or by modulation of the host’s immune system. However,
lactobacilli and bifidobacteria strains have been variously shown to influence immune
function via effects on enterocytes, regulatory T cells, effectors T and B cells and antigenpresenting cells (and this includes both circulating monocytes and local dendritic cells) [12].
On the other hand [13] proposed as a mechanism of ingestion of nondigestible carbohydrates
which enter the colon and they are fermented by colonic bacteria. The production of shortchain organic acids, lactic and butyric, which lower the colonic pH, increase in biomass, and
an environment less conducive to the growth of pathogenic bacteria are the result. In addition,
the lower pH aids ion absorption. There is an increase in intestinal epithelial cells, particularly
goblet cells whose mucus secretion coats the intestinal wall providing a thicker coat of
protection. The length and width of intestinal crypts is increased, providing an enlarged area
for absorption for both macro- and micronutrients. This process alters the energy metabolism,
gene expression and lipid and cholesterol levels, and the interaction between microbiota and
lymphatic cells is critical for the optimal functioning of the immune system [13]. Instead, [2]
suggest that probiotics are responsible for competitive exclusion of enteric pathogens from the
gut lumen. The inhibitory mechanism should be the production of lactic acid and bacteriocins
and they restore the normal intestinal flora during an antibiotic therapy, trigger cytokines
synthesis from enterocytes attaching to their surfaces, produce toxic metabolites like
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hydrogen peroxide and synthesize butyric acid which increases the turnover of enterocytes
and neutralizes dietary carcinogens [2]. The researchers believe that probiotics are responsible
of several immunomodulatory functions acting on cellular and humoral responses and they
can stimulate Type 1 Helper T Cells (Lb. casei), mononuclear cells leading to increased
clearance of circulating pathogenic bacteria (Lb. acidophilus), macrophages to produce
TNF-alpha, IL-6 and NO production, increase clearance of circulating pathogenic bacteria
by Kupffer Cells and they can produce antirotaviral IgA and antinfluenza IgG antibodies
(B. breve).
Marco and Tachon (2013) [14], proposed another mechanism of probiotic which
conferred health benefits. This mechanism includes modulation of immune response
pathways, strengthening the epithelial barrier and (in) direct effects on human pathogens.
Also, in medical literature it was reported other emerging mechanisms which include
regulating activity along the gut brain axis [15]. Chen et al. (2012) [16] suggest that the
mechanism includes energy homeostasis as well as functions which might apply to probiotics
administered at other locations on the human body [17]. In recent years, significant progress
has been made toward the identification of the probiotic cell components responsible for these
effects [18].
West et al. (2012) [19] thinks that the above observations translate into clinically relevant
effects needs further study. However, it is not known to what degree effects of a specific
probiotic strain are relevant for other strains, even of the same species. Therefore, effects
should be considered strain-specific at this stage. In conclusion, in future evaluating the
effects of probiotics in clinical trials is very important because immune stimulating effects of
probiotics in in vitro studies can be divergent from those observed in vivo [19].
3. Probiotic microorganisms
Probiotic microorganisms used in food must be able to survive the passage through the
gut; i.e., they must have the ability to resist gastric juices and the exposure to bile [20]. Also,
they must be able to proliferate and colonise the digestive tract. In addition, they must be safe
and effective, and maintain their effectiveness and potency for the duration of the shelf-life of
the product [21]. Holzapfel et al. (2001) [22] reported that most commonly micro-organisms
used as probiotics belong to the heterogeneous group of lactic acid bacteria (genera
Lactobacillus and Enterococcus) and to the genus Bifidobacterium. Each group involves
different species (Lactobacillus acidophilus, Bifidobacterium bifidus etc.) which include
different strains. Today many other microorganisms are known as probiotics [23, 1].
Lactobacilli are Gram-positive lactic acid producing rod-shaped bacteria. They are part of but
not the dominant species of the normal microbiota of the mouth, the lower small bowel, colon
and vagina in some but not all individuals. Lb. acidophilus and bifidobacteria constitute 90%
of the colonic organisms in breast-fed infants. Lb. casei significantly enhances the immune
system and stimulates the production of Immunoglobulin A (IgA). The fermentation of the
non digestible carbohydrates constitutes their principle source of energy production and,
notably Lb. acidophilus and Lb. johnsonii, contain proteinases and are able to degrade the
harmful bacteria polypeptides. Lactobacilli are important in the food industry where they are
used in the pickling process and for cheese and yogurt production [13]. Ma et al. (2004) [24]
suggest that Lb. reuteri has anti-inflammatory properties, as demonstrated in animal and
human in vitro studies. The researchers reported that Lb. reuteri prevents TNF-α– induced IL-8
expression in murine epithelial cells. Then diminishes inflammatory bowel disease in murine
models [25], and after that induces human IL-10 producing regulatory T cells by modulating
dendritic cell function [26].
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Bifidobacteria are Gram-positive, nonmotile, nonspore forming, catalase negative,
polymorphic rods in a Y or V shape and hence the name ‘bifid.’ They are compulsory
anaerobes though some can tolerate low levels of oxygen. Ingested bifidobacteria can pass
through the stomach’s acid and the unfriendly bile salts and once in the colon, they bind to the
epithelial cells and to the intestinal mucin. Their density in the human GIT varies with age,
diet, lifestyle, and activity [13]. High quantities of Bifidobacterium spp. cells and the recent
evidence indicate that Ruminococcus spp. also colonizes in abundance the colons of breastfed infants. Newborns on formula have a varied microbiota but far less of these friendly
bacteria. The intestinal microbiota of adult organisms consists of enterobacteria and coliforms
and fewer numbers of lactobacilli and bifidobacteria. Bifidobacteria species are able to
ferment oligosaccharides and other complex nondigestible carbohydrates such as resistant
starches, raffinose, lactulose and intestinal mucins [13].
Up to 30 different bacterial species have been reported, isolated from sewage, human and
animal feces, rumen of cattle, dental caries and honey bees. The most frequently reported
Bifidobacterium spp. as having health benefits is B. longum. Protective functions include
competing with harmful bacteria for nutrients, colonization numbers and adherence to
the intestinal epithelium. Control of epithelial cell proliferation and differentiation and
homeostatic regulation of the immune system are tropic functions. Bifidobacteria expand the
number of mucosal lymphocytes, the size of germinal centers in lymphoid follicles and there
is some research indicating a role in the induction of regulatory T cells in lymph follicles [13].
Other less commonly used probiotic microorganisms are strains of: Streptococcus spp.,
Bacillus spp. and Saccharomyces spp. Streptococcus thermophilus has been used in probiotics
to enhance digestion of lactose in intolerant subjects [27].
Saccharomyces boulardii is considered probiotic yeast but is not a normal or usual
resident of the gastrointestinal tract (GIT) ecosystem. If used, it must be given continuously as
within 6 h after the last dose because it cannot be found in the intestinal lumen [13].
Probiotics microorganisms are available in food and dietary supplements (for example,
capsules, tablets and powders) and in some other forms as well. In foods and supplements, the
bacteria may have been present originally or added during preparation. Probiotics microorganisms
must survive of the gastric and bile acids in order to reach the intestinal tract colonize the host
epithelium and exhibit a beneficial effect [23].
4. Probiotics and immune system
One of the environmental factors that may influence the risk of developing different
disease is the gut microbiota. Wohlgemuth et al. [9] proposed that probiotics exert their effect
by modulating gut microbiota composition and a considerable number of studies support this
assumption by demonstrating changes in a number of bacterial groups in response to the
consumption of probiotics. Yamano et al. (2006) [28] observed that the numbers of
bifidobacteria and lactobacilli increase in healthy subjects after ingestion of Lb. casei Shirota
or Lb. johnsonii La1 while those of numbers of enterobacteria or clostridia decrease.
Kuhbacher et al. (2006) [29], reported that the probiotic preparation VSL#3 which
consists of four Lactobacillus spp. (Lb. acidophilus, Lb. plantarum, Lb. paracasei and Lb.
delbrueckii subsp. bulgaricus), three Bifidobacterium spp. (B. breve, B. longum and B.
infantis) and Streptococcus thermophiles are effective in elevating the number of total gut
bacteria and in restoring the intestinal microbiota diversity in pouchitis patients. Also, VSL#3
increases caecal bifidobacteria numbers and modifies the metabolic activity of caecal bacteria
in mice with chronic colitis induced by dextran sulphate sodium (DSS) [30].
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Herrick and Bottomly (2003) [31] believe that oral tolerance is present from the first
hours after birth and not only gives way to the suppression of immune response against
proteins, introduced with nourishment, but also acts against the microbiota that can modulate
the immunologic aspect, favoring tolerance itself. Also, oral tolerance to an allergen can block
immunologic response outside the gastrointestinal environment, such as in respiratory and
cutaneous apparatus. Noverr and Huffnagle (2004) [32], reported that immunologic tolerance,
including oral tolerance, is likely mediated by a large group of T cells originated from
dendritic cells (DCs), which show antigen (antigen-presenting cell). Then immature DCs,
which have not received inflammatory stimuli, mature also in the intestinal mucosa and
originate regulator DCs, DC type 1, and DC type 2, with regard to the interactions among
pathogenic, different, and/or microbial products [33, 34]. They can originate also regulatory T
cells, through interleukin (IL) 10 and/or transforming growth factor-β, and type 1 (Th1) and
type 2 (Th2), through the production of cytokine [32].
For humans, [12] suggest that the gut-associated lymphoid tissue (GALT) accounts for
two-thirds of the immune system, reflecting the enormous immunological challenge conferred
by the intestinal luminal contents especially in early infancy when this is established. Also,
gut microbiota confer specific immune-protective effects that are likely to be mediated
through complex pathways within and even beyond the GALT. This encompasses effects on
local IgA production, induction of tolerogenic dendritic cells and regulatory T-cell populations
with the production of immunomodulatory cytokines such interleukin 10 (IL-10) and
transforming growth factor beta (TGF-b). The mechanisms described above need further
study, because they appear to modulate local inflammation, maintain gut barrier mechanisms
and consequently reduce the risk of maladaptive systemic immune responses [3].
Lammers et al. (2005) [35] studied the mucosal gene expression of the pleiotropic
proinflammatory cytokines (interleukin (IL)-1beta, IL-6), TH1 cytokines (interferon-gamma
(IFN-gamma), TNF-alpha, IL-12), regulatory cytokines (IL-10, transforming growth factorbeta) and the chemokine IL-8. Also, itwas evaluated the presence of polymorphonuclear cells
in the mucosal tissue. The researcher reported that probiotic treatment is able to regulate the
mucosal immune response reducing mucosal levels of neutrophil chemoattractant IL-8 and
tissue influx of polymorphonuclear cells, and may further act as an inhibitor for the inhibit T
cells activation, reinforce the barrier function and keep a tight control of the potent
proinflammatory cytokine IL-1beta.
Another study consisting in a randomized double-blind study was designed by [36].
Probiotic bacteria or placebo were administered for 1 month before delivery to mothers and
for 6 months to infants with a family history of allergy. Study by [36] highlights the role of
chronic microbial exposure as an immune modulator protecting from allergy.
Makino et al. (2010) [37] studied two independent groups involved 142 elderly
individuals who were given either yogurt (90 g) fermented with Lb. delbrueckii or milk (100
mL) daily over an 8–12-week period. The researchers observed an increased in natural killer
cell activity in the yogurt group (p=0.028) and their risk for catching the common cold was
2.6 times lower than in the milk group [37].
Abrahamsson et al. (2012) [38], suggest that a high gut microbial diversity might be more
important than the absence or presence of specific genera or species in the context of immune
system maturation and subsequent development of allergic disease. In conclusion, it can be
assessed that there is evidence which certifies that normal immune regulation relies on
“optimal” gut microbiota and may be influenced by differences in early colonization patterns.
This has been the logical basis for the concept of probiotics in treatment and prevention of
disease [3].
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5. Beneficial effects of probiotics on health
In recent years a variety of pharmaceutical and medicinal applications have been
identified though, probiotics were explored in the beginning for the ‘beneficial health effects’.
On the basis of different microbial characteristics, various forms of formulations are being
developed for variety of clinical conditions. Differential species with variable characteristics
are indicated for different clinical conditions [39]. Unfortunately, investigators who have used
probiotics as intervention in treatment of the same disease or conditional though they have not
used the same species of bacteria but often different combinations of organisms, different
quantities and varied lengths of therapy. This has often resulted in conflicting results and
difficulties in interpreting the degree of benefits to health. In selecting which probiotic might
be appropriate for a given study several criteria are important, namely [13]:
¾ Survival of the ingested beneficial bacteria depends on the degree of tolerance to acids
and bile.
¾ Survival of harmful bacteria is influenced by which bacteria have the greater ability to
metabolize nutrients not digested by the host and which bacteria can better adhere to
intestinal cells.
¾ Also, survival in the competitive environment is dependent on which probiotics
produce bacteriocins, a proteinaceous antimicrobial compounds that protect against
pathogenic bacteria and which bacterium is a better scavenger of iron and can thus
deprive other bacteria of this vital mineral.
On the basis of different microbial characteristics, differential species and various forms
of formulations for variety of clinical conditions various diseases where used probiotics for
treatment are described as follows:
Skin disease
Wilson (2008) [40] mentions that the skin is the largest human organ and is in direct
contact with the environment; it is inhabited by and constantly exposed to microorganisms in
the environment. The resident skin microbiota interacts with other microbes, with human cells
and with the human immune system in multiple ways that mediate risk of disease.
The microbial diversity present in and on humans is associated with several infectious
and non-communicable diseases. Changes in resident microbial communities have been
shown to be associated with skin conditions such as acne, atopic dermatitis and psoriasis [41,
42]. Even more broadly, The Human Microbiome Project has inspired exciting new studies
demonstrating how changes in resident microbial communities play a role in disease,
including antibiotic-associated diarrhea, bacterial vaginitis, human immunodeficiency virus,
obesity and cardiovascular disease [43, 44].
Atopic dermatitis
Baquerizo Nole et al. (2014) [45] reported that probiotics appear to be effective in
reducing the incidence of atopic dermatitis in infants, but their role in atopic dermatitis
treatment is controversial. Their role in acne, wound healing and photoprotection is promising,
but larger trials are needed before a final recommendation can be made.
In medical literature data exist showing the protective effect of probiotics in the incidence
of pediatric atopic dermatitis (PAD), there is less convincing information about their effects
as treatment [45]. However, [46] reported that Lb. plantarum strain was used for 12 weeks in
treatment of 83 children with PAD and showed a reduction of 9.1 in scoring atopic dermatitis
(SCORAD index) at week 14, compared with a 1.8 reduction in SCORAD index in the
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placebo group. Also, [47] found that a probiotic mixture reduced SCORAD index of 38
patients with moderate to severe atopic dermatitis (AD) and similar results in 48 AD patients
reported [48]. Also, [49] studied the effects of probiotics in AD in a randomized double-blind
study. A number of 27 infants (mean age, 4.6 months) who presented with AD during
exclusive breast-feeding was divided into 3 groups: probiotic-supplemented, B. lactis Bb-12
strain or Lb. rhamnosus GG (LGG) strain and extensively hydrolyzed whey formulas or the
same formula without probiotics. A significant reduction in SCORAD index was seen after 2
months for the probiotic-supplemented groups as compared with the unsupplemented group
(P = .002).
The conclusion is that existing studies on the potential therapeutic effect of probiotics are
generally promising, but all scientific researcher agree that there is not enough evidence to
reliably assess the possible role of probiotics in the treatment of skin allergic disorders and
that further studies should be done with a higher number of patients to get more reliable
results [50].
Gerasimov et al. (2010) [51] performed a single trial that involved 90 children between
1 and 3 years of age with moderate-to-severe AD. The experimental group received Lb.
acidophilus and fructo-oligosaccharide as supplements for 8 weeks. The children who
received synbiotic therapy decreased their SCORAD by 33.7%as compared to the control
group whose score decreased 19.4% and the symbiotic group used less topical corticosteroids.
These changes were also associated with a change in lymphocyte subsets. However, the daily
administration of LGG for 4 weeks decreased SCORAD in the children with high IgE levels
[52]. On the other hand, no improvement of SCORAD and of inflammatory parameters was
observed in infants less than 5 months of age who received a hydrolyzed, whey-based formula
alone or supplemented with LGG or with Lb. rhamnosus strain for 3 months [53].
Acne
The main factors involved in acne are: excess sebum production, follicular
hyperkeratinization, Propionibacterium acnes hypercolonization and inflammation [54]. Wang
and Wu (2005) [55] observed that these factors may be aggravated with stress. Stress can also
alter the intestinal lining, by encouraging bacterial over growth, stagnating intestinal transit
time and thereby compromising the intestinal barrier [55]. One of the potential benefits that
systemic probiotics may offer is the reduction of inflammation in acne, probably caused by
the down regulation of gene expression related to the release of inflammatory cytokines and
the recruitment of pathogenic CD8 T cells while activating Treg cells [56]. Kim et al. (2010)
[57] observed at significant improvement (statistically) in inflammatory lesion count, total
lesion count and clinical grade of acne after daily consumption of Lactobacillus spp, for 12
weeks compared to fermented milk (placebo) consumption. Also, Di Marzio et al. (1999) [58]
reported that the application of topical probiotics, such as S. thermophilus, increased ceramide
production when applied for 7 days as a cream.
Eczema
Several studies have been published using probiotics in medical literature and majority of
studies evaluated Lactobacillus strains alone or in combination with other probiotic species.
Woo et al., (2010) [59] demonstrated that Lb. fermentumand Lb. sakei strain can to reduce
SCORAD index significantly.
In two other studies it has been observed that probiotics are only effective in children
with food sensitization. In a Finnish randomized controlled study, LGG was effective in
preventing the development of eczema in a breast-fed child when the mother was given LGG
4 weeks prenatally and 6 months postnatal. In a double-blind, prospective, randomized study
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with breast-fed children and cow's milk allergy, a significant increase of interferon-γ was
measured [49]. Zhu et al. (2010) [60] carried out a meta-analysis on 12 RTC trials, seven of
which reported that lactic acid bacteria but only when used in combination with other
probiotics had a positive effect on the prevention of eczema; compared to the placebo, the
relative risk (RR) was 0.79. When mothers were given LGG prior to delivery and during
lactation (23 vs 46% in the probiotic and placebo groups, respectively) a decrease of atopic
eczema in infants from atopic families was observed [61].
Gastrointestinal diseases
H. pylori is considered as the etiological factor for gastro duodenal ulcers and a risk
factor for gastric cancer, due to the early colonization process and an important factor in
determining the development of gastric cancer later in life [62].
In the medical literature was reported that in the treatment and prevention of H. pylori
infection lactobacillus species and bifidobacteria help and make a direct, non-specific,
bacteriostatic activity, increased Ig A production or have an inhibitory effect on attachment of
H. pylori [39]. Zou et al. (2009) [63] reported that using Lactobacillusspp. probiotic strains as
the supplements to triple therapy identified eight Randomized controlled trials (RTCs) with a
total of 1372 patients. This probiotic was more effective than the control group in improving
the eradication rate of H. pylori; 82.26% versus 76.97%. As with S. boulardii, diarrhea was
less in the group that received the Lactobacillus spp. [64] tested Lb. johnsonii NCC533 alone
or combined with cranberry juice and reported an eradication of H. pylori in 14.9 and 22.9%,
respectively, of colonized children. Also, in a randomized, double blind place to controlled
trial carried out in asymptomatic colonized children, it was shown that 4-weeks administration
of Lb. johnsonii NCC533 significantly decreased H. pylori colonization compared with the
placebo (65).
All studies reported above suggest that some probiotics may be useful to maintain low
levels of H. pylori and to decrease the chronic inflammatory processes in the gastric antrum of
colonized children. Also, better designed studies with adequate sample sizes are necessary to
obtain more solid conclusions [62].
Ulcerative colitis (UC) and Crohn’s disease (CD) are the two most frequent causes of this
chronic inflammation of the gastrointestinal tract; these are lifelong diseases characterized by
recurrent episodes of diarrhea, frequently with blood in the feces, abdominal pain, fever,
malaise and weight loss [62].
Also, studies have shown some promise for probiotics in the treatment of ulcerative
colitis (UC). Kruis et al. (2004) [66] used the probiotic strain E. coli Nissle 1917 (ECN) at
low dose of 1.5 g/day and observed that was as effective as mesalazine (intestinal antiinflammatory) in maintaining the recovery of the ulcerative colitis for a period longer than
one year. Also, in another study, Lb. rhamnosus GG exhibited a beneficial effect equivalent to
mesalazine in terms of remission of UC patients [67].
Pronio et al. (2008) [68] showed that the administration of VSL#3 for patients with ileal
pouch-anal anastomosis for ulcerative colitis had significantly increases the number of
mucosal regulatory T cells, indicating a potential beneficial immuno-regulatory mechanism of
probiotic strains in this disease.
Instead, [69] have reported that combination of the probiotic product VSL#3 (at 6 g/day)
with the intestinal anti-flammatory, mesalazine (4 g/day) in 40 patients have reduced to 10%
the post-operative recurrence of Crohn’sdisease (CD) as compared to 40% in patients treated
with antibiotic only. In a randomized controlled trial (98 patients) the ineffectiveness of Lb.
johnsonii LA1 for prophylaxis of post-operative recurrence in Crohn’s disease was studied by
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[70]. After six months of treatment with LA1, the results showed an endoscopic recurrence
rate of 64% in placebo group versus 49% in the LA1 group (p = 0.15). The results obtained in
the treatment of CD in the active stage or in remission are similar to those observed in UC. In
some cases, the efficacy is not evident. It is possible to observe a certain degree of decrease of
relapse rates but this is not clear-cut. Another problem is the small number of patients
participating in some studies [71].
Cancer
Probiotics play a protective role through the binding and/or degradation of carcinogens,
many of them originating from the western type diet, rich in red meats processed by broiling.
Many studies in mice indicate that the use of some lactobacilli reduce the uptake of mutagens
by different tissues. After observations in human volunteers [72] showed that consumption of
preparations containing lactobacilli reduces the urinary and fecal excretion of mutagenic
compounds.
Pool-Zobel and Sauer (2007) [73] performed in vitro and in vivo investigations, the
SYNCAN project, in both animal models and human clinical trials. B. lactis Bb12 and Lb.
rhamnosus GG and the combination of both (synbiotic) were incubated with a prebiotic
mixture of oligofructose and inulin (Synergy). The fermentation supernatant contained a large
quantity of butyrate and was placed in a tube with human HT2 cancer cells. Survival of tumor
cells was impaired and proliferation of cells was inhibited. Rats given colon carcinogens and
fed inulin-type fructans showed a marked reduction in the incidence of colon cancer. Humans
with colonic polyps given a synbiotic regimen showed a clear reduction in cellular DNA
damage. These authors propose long-term prospective trials to determine if such a dietary
change can reduce the rate of colon cancer [73].
Although the evidence for beneficial effects of probiotics in human tumorigenesis is
indirect, there is an accumulating body of information from experimental models that
suggests that they have anti-neoplastic effects [62].
Bacterial vaginitis
Lactobacillus spp, are the prominent microbial factors that governs the presence,
growth, colonization and persistence of non-endogenous microorganisms in vagina. As the
Lactobacillus spp. count decreases, the protection provided by them against uropathogens
also decreases. It is also proposed that lactobacilli produce biofilms, which cover the
urogenital cells [39].
Anukam et al. (2006) [74] treated 40 women diagnosed with bacterial vaginitis (BV) (it
is particularly common condition in black women and in Nigeria it isoften caused by
mycoplasma, as well as Atopobium spp., Prevotellas pp. and Gardnerella spp.) by discharge,
fishy odor, sialidase positive test and Nugent Gram stain scoring. Patients were randomized to
receive eithertwo dried capsules containing Lb. rhamnosus GR-1 and Lb. reuteri RC-14
strains each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day, in
the morning and evening. The follow-up at day 6, 15 and 30 showed a significant cure for BV
in probiotic lactobacilli treated subjects compared to metronidazole treatment. This is the first
report of an effective (90%) cure for BV using probiotic lactobacilli. The researchers
conclude that, given the correlation between BV and HIV and the high risk of the latter in
Nigeria, intravaginal use of lactobacilli can provide women with a self-use therapy, similar to
over-the-counter anti-yeast medication, for treatment of urogenital infections [74]. Also,
Oduyebo et al. (2009) [75] studied 24 RCTs that involved 4422 participants with the
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experiment group receiving antibiotics with or without probiotic Lactobacillus spp. When
given vaginally as a gelatin tablet, this probiotic was more effective than oral metronidazole
with a relative risk (RR) of 0.20. When given orally in combination with oral metronidazole,
the RR was 0.33 as compared with metronidazole alone.
Larsson et al. (2008) [76] investigated firstly if supplementary lactobacilli treatment could
improve the initial cure rate after vaginal clindamycin therapy. In secondly step, it was studied
if the lactobacilli as repeated adjunct treatment during 3 menstrual cycles could lengthen the
time to relapse after initial cure. A 100 BV diagnosed women were offered vaginal
clindamycin therapy followed by vaginal gelatin capsules containing either 109 freeze-dried
lactobacilli or identical placebo capsules for 10 days during 3 menstrual cycles in a doubleblind, randomized, placebo-controlled trial. The researchers observed that supplementary
treatment, combining two different strains of probiotic lactobacilli, does not improve the
efficacy of BV therapy during the first month of treatment, but for women initially cured,
adjunct treatment of lactobacilli during 3 menstrual cycles lengthens the time to relapse
significantly (more women remained BV free at the end of the 6-month follow up) [76].
6. Conclusions
As supplements different probiotics have been administered under controlled conditions
to a large number of patients, both adults and infants, suffering from a variety of diseases and
it have been proven to be without any associated risk. In the medical literature many studies
are reported on the potential therapeutic effect of probiotics and these being generally
promising. However, all scientific and medical researchers agree that there is not enough
evidence to reliably assess the possible role of probiotics in the treatment of all health
disorders and that further studies should be done with a higher number of patients to get good
and more reliable results for health patients.
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