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Educational

Forum

Probiotics: Making a comeback

comeback

A.K. Sharma, P. Mohan, B.B. Nayak

ABSTRACT
Department of Pharmacology,
Armed Forces Medical College,
Pune-411040.
Received: 18.4.2005
Revised: 18.9.2005
Accepted: 19.9.2005
Correspondence to:
Ashok Kumar Sharma
E-mail:

ashse16@rediffmail.com

Probiotics are nonpathogenic microbes used to confer health benefits to the recipient. The
derangement of normal body flora has been held responsible for causation of various disorders. Probiotics have been tried in a number of infective and noninfective disorders and
found useful, primarily because of their ability to supplement the normal body flora. Their
use offers various advantages over-existing antimicrobial agents in being relatively cheap
and safe. However, there are few reports of systemic fungemia associated with their use
especially, in immunocompromised and severely debilitated patients. They also carry a risk
of transferring resistance to other microbes including pathogens. In conclusion, more studies are required to establish their definite place in therapeutics.

KEY WORDS: Bifidobacterium, Lactobacilli, microflora, Saccharomyces .

Introduction

Prerequisites of probiotic

Introduction of antibiotics brought revolution in the

treatment of infectious diseases. The dramatic results of
chemotherapy lead to an enhanced interest and funding in this
field and its rapid development.
However, the use of antimicrobial therapy is associated
with the risk of increased incidence of drug resistance and
opportunistic infections,[1] which can be avoided if the use of
the antimicrobial agents can be minimized. One of the
contributory factors for acquiring the infections is the decrease
in the normal microflora at various sites in the body.
The nonpathogenic, micro-organisms or microbial mixtures
may be used to improve microbial balance and to confer health
benefits to the recipient. The microbes used for this purpose
are called probiotics. (The term probiotic in Greek means
for life.)

A microbe may be used as a probiotic if it has been

scientifically demonstrated to be having beneficial physiological
effects and safety. It should preferably be nonpathogenic, of
human origin, stable in acid and bile and be able to adhere to
human mucosa[4] also should retain viability during storage and
use.[5]

History
Benefits of using fermented milk products and poultices
of mould breads have been known since long. However, nobel
laureate Elie Metchnikoff gave the first account of practice of
probiotic therapy via fermented milk products in 1907.[2]
Application of this therapy to urogenital infections dates back
at least to 1915.[3]
However, due to increased interest in antibiotics, only few
studies were done on probiotics in the intertwining period of
7-8 decades, and this field was labelled as alternative
medicine.
There is a recent resurgence of interest in probiotics due
to consumer demand for better therapies and problems like
drug resistance and opportunistic infections.
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Probiotics as therapeutic tools

Probiotics are under study for a variety of
pathophysiological states. Their status in various conditions,
where they have the potential to establish their place more
firmly, are discussed below.
Urogenital infections
Incidence of nonsexually transmitted urogenital infections,
including urinary tract infections (UTI), bacterial vaginosis (BV)
and vaginal candidiasis, is estimated to be quite high (around
1 billion per year) around the world.[3]
The ready availability and efficacy of antimicrobials has
limited the attention paid to probiotics for UTI and BV. However,
probiotics have been found to have a definitive role in the
management of these diseases especially in recurrent and
chronic cases.
Prevention of UTI
A number of clinical studies with Lactobacilli have shown
encouraging results in preventing the recurrence of UTI.
Intra-vaginal insertion and perineal implantation of
Lactobacilli GR1 strain twice weekly in patients suffering from
recurrent UTI have been shown to result in infection free periods
ranging from 4 weeks to 6 months.[6]

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In another randomized double blind study conducted in 55

women taking Lactobacillus GR-1 and B-54 strains weekly/
twice weekly by vaginal insertion, the mean incidence of UTI
was reduced by 79%.[7]
Reid and Bruce also demonstrated that the administration
of Lactobacilli as vaginal suppositories after treatment with
antimicrobial agents reduced the recurrence rate to 21% as
compared to 47% seen in control group.[8]
The above reports confirm the usefulness of probiotics in
UTI but the number of studies is limited and more work needs
to be done to establish their role.
Prevention of bacterial vaginosis and candidal vaginal
infections
Majority of women, especially in the first part of their
menstrual cycle, have transient abnormal pattern of vaginal
flora resembling in some cases to bacterial vaginosis. In most
of these cases, vaginal flora reverts back to normal pattern,[9]
but if a probiotic may also be a natural means of correcting
this abnormality and maintaining urogenital health.
Reid G et al demonstrated that daily oral administration of
L. rhamnosus GR-1 and L. fermentum RC-14 improved vaginal
flora and lowered yeast and coliform count.[10] On oral ingestion,
these microbes pass through the gut and ascend from rectum
to vagina and colonize there.[11]
In another comparative study, prophylaxis of recurrent
candidal vaginitis and recurrent BV was studied between
groups taking yogurt enriched with H2O2 producing Lactobacilli
and pasteurized yogurt. After one month of study, 25% women
in enriched group had an episode of BV as compared to 50% in
pasteurized yogurt group (p=0.04). However, reduction in
percentage of women with candida positive cultures in both
groups was same, indicating that perhaps nonviable yogurt
cultures also have an anticandidal effect.[12]
Hilton et al administered Lactobacilli for a longer period
and studied the incidence of candidal vaginal infections. One
group of patients consumed H2O2 producing Lactobacilli and
another group consumed no yogurt for 6 months and then
both groups mutually crossed over. The number of candidal
vaginal infections per patient was 0.38 in yogurt group and
2.54 during no yogurt period (p=0.001).[13]
Since only few strains of Lactobacilli have been shown to
be effective in bacterial vaginosis and vaginal candidiasis, more
studies are warranted before such an approach can be
recommended for routine use.
Treatment of bacterial vaginosis
Bacterial vaginosis is effectively treated with metronidazole
and clindamycin, but it is associated with adverse effects and
frequent recurrences. A number of studies have shown that
probiotics if taken with antimicrobials can reduce the risk of
vulvo-vaginal perturbations.
Hillier et al. found that the incidence of vaginal infection in
pregnant women was inversely related to the intravaginal
presence of H2O2 producing Lactobacilli.[14]
Neri et al. (1993) also demonstrated higher success rate
of 28/32 in pregnant bacterial vaginosis patients taking
Lactobacilli acidophilus yogurt two doses for 7 days as
compared to 12/32 in placebo group.[15]
In spite of probiotics being useful in treating and preventing
urogenital infections,[16] the lack of knowledge about them

Probiotics

amongst physicians limits their use in day-to-day practice and

retards their growth.[17]
Diarrhea
Diarrhea is a common gastrointestinal problem, especially
in the developing world. It can result from multiple aetiologies.
Probiotics have been shown to prevent and assist the recovery
from many types of diarrheas.
Infectious diarrheas
In developing countries, incidence of infectious diarrhoea
is very high due to poor sanitation and nutrition. The problem
is best addressed by improving sanitation and nutrition but an
inexpensive and effective probiotic also has a value.
Probiotics have been shown to reduce the incidence of
diarrheal episodes and facilitate the recovery when used as
an adjunct to oral rehydration therapy for acute diarrheas.
Lactobacilli GG, Bifidobacterium and Streptococcus
thermophilus have been shown to reduce the incidence of
diarrhea as compared to control groups.[18, 19] The use of
Bifidobacterium and Streptococcus thermophilus also reduced
rotavirus shedding.[19]
The recovery (in terms of reduction in duration of diarrhea)
from acute diarrheas has been shown to be facilitated by
Lactobacilli GG, L. reuteri, L. casei and S. boulardii.[20]-[23]
In AIDS-associated diarrhea, S. boulardii has been found
to help resolution in 10 of 18 patients as opposed to 1 of 11 in
placebo when administered for 1 week.[24] In another study,
patients with HIV-related chronic diarrhea, Elmer et al. found
it to be useful in 7 of 11 patients but in 24 weeks.[25]
The role of E. faecium SF68 in acute diarrhea cannot be
ignored. It has been found to be effective in reducing diarrhea
in adults after 1 week of treatment (0.6% in treatment group
and 8.7% in placebo group, P=0.01); [26] however, it was not
found to be useful in patients infected with V. cholerae /ETEC
after 3 days treatment.[27]
Antimicrobial agent associated diarrhea
Diarrhea is one of the most common adverse effects of
antibiotic therapy. The precise mechanism is not known;
however, perturbation of normal intestinal flora leading to the
following events seems to be responsible.
1. Decrease in short chain fatty acid produced by normal flora.
These fatty acids are important for the nutrition of the
enterocyte and for the absorption of water and electrolytes.
[28], [29]

2. Loss of carbohydrate digesting gut bacteria leading to

osmotic diarrhea.[30]
3. Direct stimulation of gut motility: For instance,
erythromycin acts as motilin agonist to produce diarrhea.[31]
The re-establishment of gut flora and cure of antimicrobial
agent associated diarrhea (AMAAD) has been an area of interest
since long. Anecdotal evidence indicates that consumption of
commercial unpasteurized yogurt is helpful in AMAAD.
Saccharomyces boulardii has reduced the incidence of
diarrhea in patients taking tetracyclines or b-lactam antibiotics
to 4.5% as compared to 17.5% with placebo.[32]
L. rhamnosus GG taken as yogurt has been shown to have
a beneficial effect in volunteers on erythromycin.
The group taking erythromycin and L. rhamnosus GG had
diarrhea for 2 days instead of 8 days as seen in control group
taking erythromycin and sterilized yogurt.[33]
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Sharma et al.

Bifidobacterium longum in the form of fermented yogurt

has also been found to be useful in reducing stool frequency
and abdominal discomfort in a crossover study involving 10
volunteers receiving erythromycin.[34] However, in volunteers
taking clindamycin, B. longum in combination with Lactobacilli
acidophilus was more effective than when given alone and in
comparison to placebo and produced least derangement of
intestinal microflora and lower incidence of gastrointestinal
discomfort.[35]
E. faecium is another strain having a beneficial role in
AMAAD. Wunderlich et al. (1989) found E. faecium SF68 to
reduce the incidence of antibiotic associated diarrhea from
27.2% in placebo group to 8.7% in treatment group. [26]
Cl. difficile associated diarrhea and colitis
Cl. difficile associated disease (CDD) is almost always
initiated by antimicrobial therapy. It consists of simple diarrhea
that may progress to colitis, pseudomembranous colitis and
toxic megacolon.[36] Probiotics in various clinical studies have
been found to have beneficial role in the management of CDD.
Prevention of CDD
In patients receiving antibiotic therapy, consumption of
probiotic containing both Lactobacilli and Bifidobacterium has
been associated with lower incidence of positivity for Cl. difficile
associated toxins in stools. [37]
Treatment of CDD
Metronidazole (first choice) and vancomycin (second
choice, for cases resistant or not tolerating metronidazole or
in whom it is contraindicated) are adequate treatment for the
first episode of CDD. However, antibiotic treatment has a
recurrence rate of about 20% in whom multiple recurrences
are the rule. [36] For prevention of recurrences, no simple
treatment is uniformly effective, so probiotics are being tried
to break the cycle of recurrence.
Saccharomyces boulardii when administered as 1 g/day
for 4 weeks along with standard course of metronidazole or
vancomycin in the treatment of CDD resulted in lower relative
risk (RR) of recurrence than placebo group (RR 0.43; 95%
confidence interval 0.200.97).[38] The efficacy of S. boulardii
was significant (recurrence rate 34.6%, compared with 64.7%
on placebo; p=0.04) in patients with recurrent CDD, but not
in patients with initial CDD (recurrence rate 19.3% compared
with 24.2% on placebo; p=0.86).[ 38]
In another study, to further refine a standard regimen of S.
boulardii and vancomycin; a group of patients received
vancomycin (2 g/day) for 10 days and then additional S.
bourlardii (1 g/day) for 28 days or placebo. A decrease in
recurrence rate was obser ved in patients treated with
vancomycin and S. bourlardii (16.7%) compared with those
who received vancomycin and placebo (50%; p=0.05). [39]
L. plantarum 299v has also been found to reduce the
recurrence of CDD but the number of patients studied is
small. [40]
Probiotics, at present, in spite of their documented
beneficial effects in CDD, are not recommended for routine
prophylactic use for want of larger studies.
Travelers diarrhea
In contrast to AMAAD and CDD, travelers diarrhea is
caused by the introduction of pathogenic bacteria through food
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or water that overwhelm the protective effects of normal

intestinal flora.
In a study conducted on 225 Americans, the group taking
L. rhamnosus GG had a lower rate of diarrhea per day as
compared to the placebo group (3.9% vs. 7.4%, respectively,
p=0.05).[41]
Similar larger study conducted in travelers from Austria
revealed that the group given lyophilized S. boulardii 1 g/day
had diarrheal rate of 28.7% as compared to 39.1% in placebo
group (p=0.02).[42]
Study conducted in travelers from Turkey also
demonstrated that Lactobacilli GG use reduced the incidence
of diarrhea to 41% as compared to 46.5% in placebo group
with overall protection rate of 11.8%.[43]
Lactose malabsorption associated diarrhea
Enterocyte lactase activity declines throughout childhood,
hence 90% of Africans, Asians and South American adults are
totally lactase deficient. Consumption of dairy products in such
individuals leads to signs and symptoms of lactose intolerance
such as flatulence, bloating, loose motions and at times
constipation.[44]
The use of S. thermophilus and Lactobacilli delbrueckii as
starter culture in yogurt has shown improvement in lactose
digestion.[45] The benefit is due to the presence of microbial
galactosidase (lactose) in the bacteria.
In a number of studies, better lactose digestion and
absorption and reduction in gastrointestinal symptoms have
been demonstrated in subjects who consumed fresh yogurt
(with live yogurt cultures) as compared to pasteurized product
with heat killed bacteria.[46 - 48]
Mode of action in urogenital infections and diarrheas
The beneficial effects of probiotics in UG infections and
diarrheas have been ascribed to the manipulation of local flora
composition. These changes can be achieved by the following
mechanisms.
Production of inhibitory substances: Inhibitory substances
such as organic acids, H2O2 and bacteriocins are produced
which are harmful to pathogens. L. rhamnosus GG and L. reuteri
have been found to produce inhibitory substances like microcin
and reutericin, respectively.[49, 50] Vaginal flora prevents vaginal
infections by creating unfavourable vaginal conditions for
pathogens by producing H2O2 and fermenting glycogen to
produce lactic acid and an acidic pH.
Inhibition of pathogen attachment: Competitive inhibition
of bacterial attachment sites on epithelial surfaces is another
mechanism. L. acidophilus has been shown to inhibit the
attachment of E. coli to mucosal cells in pig ileum. There is no
effect if L. acidophilus if given after attachment has already
taken place.[51]
Competition for nutrients: Probiotics also deplete nutrients,
which are essential for the proliferation of pathogens. An
example is the depletion of monosaccharides, which is essential
for Cl. difficile.[52]
Stimulation of IgA: S. boulardii has been found to stimulate
secretory IgA in small intestine in rats.[53] L. rhamnosus GG
has been found to cause stimulation of local IgA secretion in
human intestine in rotavirus infection.[ 54]
Trophic effects on intestinal mucosa: Bifidobacterium and
other probiotics have been shown to produce substances like

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butyrate, which stimulate the proliferation of normal epithelium

and play role in maintaining mucosal barrier defences.[5]
Inhibition of action of microbial toxin: S. boulardii destroys
Cl. difficile toxin A receptor in isolated rat ileum.[55]

Helicobacter pylori infections

Helicobacter pylori, which colonizes the stomach, is
implicated in the aetiology of gastric ulcers and gastric cancer.
Various preclinical studies shown that antibacterial substances
produced by some Lactobacilli inhibit the growth, colonization
and survival of this pathogen.[56]
Preliminary results in humans shown that milk fermented
with Lactobacilli johnsonii strain can help to control H. pylori
gastric infections, but cannot eradicate H. pylori.[56]
In some studies conducted on subjects positive for H. pylori,
the incidence of side effects associated with antipylori antibiotic
therapy was less when administered with Lactobacilli GG[57] or
Bacillus clausii [58] but one study failed to demonstrate any
beneficial effect of probiotic use as a supplement to the
classical triple therapy with antibiotics. [59] In lieu of above
reports, more number of studies are required to clearly define
the role of probiotics.
Inflammatory bowel disease
Inflammatory bowel disease (IBD) is a collective term used
for ulcerative colitis (UC) and Crohns disease (CD). Traditional
medication used in IBD includes 5-aminosalicylic acid (5-ASA)
and corticosteroids. Corticosteroids are very effective in inducing
remission in both UC and CD, but have no role in maintaining
remission and are fraught with many unwanted effects.[60]
There is enough evidence that IBD is caused by an abnormal
immune response to a luminal antigen and it appears that the
antigens are probably commensal bacteria. [61 - 64] In
experimental studies, it has been proved that different bacteria
elicits different types of cytokine response. In Crohns disease,
commensal E. coli strain stimulate the release of tumour
necrosis factor- (TNF-) and interleukin-8 (IL-8) by inflamed
mucosa. However, some lactobacilli strains including L. casei
down regulate the spontaneous release of TNF- by the
inflamed tissue and also the inflammatory response induced
by E. coli. [65,66] Therefore, it makes sense to either eliminate
some bacteria with antibiotics or to alter the gut flora, in favour
of more beneficial bacteria, by the use of probiotics and
prebiotics. (Prebiotics are dietar y substances usually
nondigested carbohydrates that stimulate the growth and
metabolism of protective commensal enteric bacteria.)
Clinical trials suggest that some probiotics can be beneficial
in preventing the relapse of IBD. In ulcerative colitis, oral
administration of viable E. coli strain Nissle 1917 has been
found to be as effective as mesalazine (the standard therapy
for the maintenance of remission) in maintaining remission.[67,
68]
The same probiotic also lowered the relapse rate (33% in
test group vs 63% in placebo group) in cases of Crohns
disease.[69]
Another probiotic, S. boulardii, when administered in
patients with quiescent Crohns disease as coadjuvant therapy
with mesalazine, produced lower clinical relapse rate as
compared to mesalazine alone.[70]

Probiotics

Although these initial studies show promising prospects

in IBD patients, further research on mechanism of action is
desired so as to optimize their use.
Allergy
Infants with atopic eczema or cows milk allergy have shown
that probiotics can be a useful tool in the treatment of food
allergy. In infants receiving extensively hydrolyzed whey
formula with Lactobacilli GG or Bb12, there is significant
improvement in the clinical score of atopic dermatitis and
reduction in the markers of inflammation compared with
placebo groups.[71, 72]
Rosenfeldt et al. also confirmed that administration of L.
rhamosus and L. reutri for 6 weeks in atopic children up to
13 years of age resulted in higher improvement rate of eczema
(56% compared to 15% in placebo group).[73]
The antiallergic effects of probiotics are suggested to be
mediated through the induction of regulatory T cells and
counter regulation of Th1 cells, [74] reduced immunogenicity of
potential allergens through modification of their structures [75]
strengthening of mucus defenses (production of IgA ),
stabilization of gut mucosal barrier and down regulation of
inflammatory responses.[76]
Hypertension
A large population in the world is estimated to have
hypertension. Evidence exists to suggest that some decrease
in blood pressure (BP) may result from consumption of certain
Lactobacilli, or milk fermented with Lactobacilli.
Studies with human subjects are limited. However, in one
placebo controlled trial, milk fermented with Lactobacilli
helveticus and Saccharomyces cerevisiae, reduced systolic BP
by 9.4 mmHg and 14.1 mmHg af ter 4 and 8 weeks,
respectively, and diastolic BP by 6.9 mmHg after 8 weeks of
consumption in known hypertensives.[77]
Attempts to identify the antihypertensive mechanism
suggest that it may be due to a bacterial cell wall component
or angiotensin-converting enzyme inhibiting peptides generated
by probiotics. [56]
Hypercholesterolemia
Cholesterol is a component of cell membranes and nerve
cells. It also acts as a precursor to certain hormones and
vitamins. However, elevated levels of total blood cholesterol
or other blood lipids are considered risk factors for developing
coronary heart disease.
Although humans synthesize cholesterol, diet also plays a
role in determining serum cholesterol levels. Probiotic have
been evaluated for their effect on serum cholesterol levels.
Consumption of yogurt containing E. faecium is effective in
lowering LDL and total cholesterol.[78, 79 In another study,
probiotic consumption was also found to increase HDL and
reduce the ratio of LDL to HDL from 3.24 to 2.48.[80]
Precise mechanism of this effect is not known. However,
assimilation of cholesterol by bacterial cells, deconjugation
of bile acids by bacterial acid hydrolases and inhibition of
hepatic cholesterol synthesis are some of the proposed
mechanisms. [81]

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Kidney stones

Problems associated with probiotic use

High level of oxalate in the urine is a risk factor for the

development of kidney stones. An intestinal microbe called
Oxalobacter formigenes can degrade oxalate through the
enzyme oxalyl- CoA decarboxylase and thus limits its
absorption.
Patients with calcium oxalate stone have been shown to
have lower rate of colonization with Oxalobacter formigenes.
Among stone formers, absence of intestinal Oxalobacter
correlates with higher oxalate concentration and increased risk
of hyperoxaluria.[82]
In another study, Bifidobacterium breve was found to
possess oxalate-degrading capabilities and hence has a
potential to be used as a probiotic in oxalate stone diseases
for prophylaxis against new stone formation.[83]

Viability of probiotics
An important problem with the use of probiotics is the
maintenance of their viability to produce beneficial effects to
the consumer. The probiotics need to survive in several
environments including processing treatments, storage
conditions and human body conditions (especially gastric
acidity and action of bile salts).
The ability to live through the stressful acidic conditions
and bile solutions in human body vary among the strains of
probiotic bacteria. Only those strains, which tolerate these
adverse conditions better, should be preferred.
The viability of probiotics may also be improved by using a
medium, nutrient and temperature, which supports their
survival.
Viability of Lactobacilli has been enhanced by encapsulation
in artificial sesame oil for storage and in simulated high gastric
or bile salt condition as compared to free cells.[90]
Storage at 4o C temperature is reported to be a most
important factor in keeping probiotic Bifidobacterium viable
during 4-week storage time.[91]
The use of prebiotics like isomalto-oligosaccharides has
been found to be associated with higher levels of probiotics
like Lactobaillus and Bifidobacterium after 1 month storage.[92]
The issue of viability of probiotics from the stage of
processing till it is used by the consumer to produce benefits
still remains a fertile field for more research.[91]

Cancer
Chemical exposure is a potential cause for high risk of
cancer. Chemicals causing cancer (carcinogens) can be ingested
or generated by the metabolic activity of microbes that harbor
in the gastrointestinal system.
It has been hypothesized that probiotic might decrease the
exposure to chemical carcinogens by (i) detoxifying ingested
carcinogens, (ii) decreasing the population or metabolic activity
of bacteria that may generate carcinogenic compounds, (iii)
producing compounds that inhibit the growth of tumor cells,
(iv) stimulating the immune system to defend better against
cancer cell proliferation or (v) producing metabolic products
(e.g. butyrate) which improve programmed cell death
(apoptosis).[56]
It has been demonstrated in various animal studies that
supplementation with specific strains of Lactobacilli can
prevent establishment, growth and metastasis of
transplantable and chemically induced tumours.[84]
In humans also, the consumption of fermented dairy
products containing Lactobacilli or Bifidobacterium has been
found to have inverse relationship with incidence of breast
and colon cancer.[85, 86]
As direct evidence in humans, the consumption of L. casie
fermented milk has been shown to significantly reduce the
recurrence of superficial bladder cancer. [87]
Growth and well-being
In an Indian study, involving 100 malnourished children,
the use of 50 ml of fermented curd for 6 months , produced
higher weight gain (1.3 kg vs. 0.81 kg in controls), greater
height (3.2 cm vs. 1.7 cm in placebo group), lower incidence
of diarrhea (21 vs. 35 episodes in controls) and fever (30 vs.
44 episodes in placebo).[88]
In another study, administration of milk formulae
supplemented with Bifidobacterium lactis and Streptococcus
thermophilus reduced the incidence of colic and irritability in
infants as compared to control group.[89]
These beneficial effects of probiotics may be attributed to
their ability to prevent various pathological states common in
children especially gastrointestinal infections and milk allergy.

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Safety and tolerance

Fermented dairy products and cereals have been an integral
part of food for centuries. The available probiotic micro
organisms are also considered nonpathogenic, but these can
be infective in a severely debilitated or immunosuppressed
patient. To date, there have been only isolated reports linking
probiotics with adverse effects. Some cases of liver abscess,[93]
Lactobacillemia[94, 95] and S. boulardii fungemia[96-98] have been
reported in such patients. On the other hand, S. boulardii has
been used without complications to treat chronic diarrhea in
AIDS patients.[24, 25]
Another reason of concern is the risk of transfer of
resistance via probiotic agents as these agents have to be
resistant to the antibiotics because they are to be used
alongside. In fact, a study has demonstrated transfer of plasmid
pAMb1, from L. reuteri to E. faecium and from E. faecium to
E. faecalis in mouse intestinal tract.[99]
In a long-term study, undertaken in children for 1 year,
consumption of 106109 CFU of Lactobacilli and Bifidobacteria
daily did not only result in any adverse effect but also showed
that probiotics taken over a long time improve gastrointestinal
function and reduce the incidence of diaper rash.[100]
Conclusion
Probiotics are likely to emerge as alternative to
conventional antimicrobial therapy, as they are relatively cheap
and may have lower risk of resistance due to multifaceted
mechanisms of action.

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Studies have shown their beneficial effects in urogenital

infections, diarrheal diseases, hypertension, oxalate renal
stones, allergic disorders, cancer and in children as growth
promoters. However, further studies are required to establish
their place in the management of these conditions.
Some major limitations in establishing their role in the
therapeutics may be lack of adequate knowledge about them
among prescribers, and probably the preparations available
over the counter contain nonviable organisms or strains that
possess no antipathogenic activity.
In general, the published reports suggest that the risk of
therapy with the available probiotics is small. However, the
risk of transmission of resistance and apprehension about their
use in immunocompromised patients remain as some of the
issues that need further clarification.
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