The Journal of International Medical Research

2008; 36: (Suppl 1): 1A 53A

1A
Probiotics in Clinical Practice: an
Overview
GV ZUCCOTTI
1
, F MENEGHIN
1
, C RAIMONDI
1
, D DILILLO
1
, C AGOSTONI
2
, E RIVA
2
AND M GIOVANNINI
2
1
Department of Paediatrics, Luigi Sacco Hospital, and
2
Department of Paediatrics, San
Paolo Hospital, University of Milan, Milan, Italy
The observation that intestinal bacterial
microflora might be able to influence
immune system surveillance through
changed nutritional habits has raised
awareness of the role of probiotics. These
are live microorganisms that are able to
reach the gastrointestinal tract and alter
its microfloral composition, producing
beneficial health effects when consumed
in adequate amounts. Recent clinical
trials have evaluated the clinical
effectiveness of probiotics in the treatment
and prevention of a wide range of acute
and chronic gastrointestinal diseases, and
also non-gastrointestinal diseases, such as
atopy, respiratory infections, vaginitis
and hypercholesterolaemia. Probiotic
supplements are generally regarded as
safe because the microorganisms they
contain are identical to those found in
human gastrointestinal and vaginal
microflora. Guidelines on the use of
probiotics in the clinical setting require
periodical updates for the latest data to
be included in clinical applications.
The purpose of this clinical report is
to review current evidence on the
use of probiotics in a variety of
gastrointestinal and non-gastrointestinal
conditions.
KEY WORDS: PROBIOTICS; GASTROINTESTINAL DISEASES; ALLERGY; INFECTIONS; CLINICAL TRIALS;
EVIDENCE LEVEL; CLINICAL EFFECTIVENESS
Introduction
The intestinal mucosa has a huge surface
area that is constantly exposed to antigenic
stimulation. For this reason, the
gastrointestinal tract has the most extensive
lymphoid system of the human body, known
as gastrointestinal-associated lymphoid
tissue (GALT), which has defence and
immune modulatory functions.
The main role of the gastrointestinal
system is to transform food into simpler
components that can be absorbed and used
to produce energy for cellular function and
growth. Specific immunological and non-
immunological protective mechanisms
prevent the transit of external and
unprocessed antigens across the
gastrointestinal barrier. These mechanisms
are collectively known as the intestinal
mucosal barrier, characterized by non-
specific (non-immunological) defensive
mechanisms such as intestinal motility,
mucus secretion, gastric acids and pancreatic
enzymes, and specific (immunological)
mechanisms such as immunoglobulin A
(IgA) production and antigenGALT
2A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
interactions.
1
A fundamental enteric
function, known as oral tolerance, is based
on the interaction between the intestinal
epithelium, GALT and food antigens, and
consists of a specific immunological
hyporesponsivity to mucosal antigen
exposure.
2
Oral tolerance, which starts in
early childhood, is able to suppress the
immune responses against both food
proteins and the hosts own resident
intestinal bacterial microflora. The intestinal
microflora is able to modulate the
gastrointestinal immune system towards
oral tolerance and protect the gut from
pathogenic microorganisms by
competitively excluding them from nutrients
and epithelial attachment sites (often
receptors), by producing antimicrobial
substances (bacteriocines) and by enhancing
specific antibody
3
production, while the
neuroendocrine cells increasingly activate
intestinal peristalsis.
4
The observation that intestinal bacterial
microflora might be able to influence
immune system surveillance through
changed nutritional habits has focused
scientific attention on the role of those
bacterial strains known as probiotics.
Probiotics, which means for life, are defined
as live microorganisms that are able to reach
the gastrointestinal tract and alter its
microfloral composition, producing beneficial
health effects on the host when consumed in
adequate amounts.
5
Although the term
probiotic was first used in the 1960s to
contrast with the term antibiotic, reports on
the health benefits of bacteria in food can be
found in the literature from earlier years. In
1908 Metchnikoff
6
suggested that the
longevity of Bulgarian peasants could be
related to their large consumption of sour
milk containing Lactobacillus bulgaricus.
Many microorganisms that constitute the
anaerobic intestinal microflora could be
considered as potential probiotics, but only a
few are able to satisfy specific criteria that
define probiotics (Table 1).
7
A variety of
probiotic microorganisms have been studied
as either single agents or combination
therapies. Most bacterial strains with
probiotic activity belong primarily to two
genera, Lactobacillus and Bifidobacterium
(Table 2).
8
According to the scientific
literature, the taxonomic identity, main
phenotypic features, safety and efficacy,
should be clearly defined for any probiotic
microorganism.
9
The Bifidobacterium spp. represent a major
group of saccharolytic bacteria in the large
intestine. They account for up to 25% of the
TABLE 1:
Criteria used to define whether a microorganism can be considered a probiotic
7
Be of human origin
Be non-pathogenic in nature
Be resistant to destruction by technical processing
Be resistant to destruction by gastric acid and bile
Adhere to intestinal epithelial tissue
Be able to colonize the gastrointestinal tract, even in the short term
Produce antimicrobial substances
Modulate immune responses
Influence human metabolic activities (i.e. cholesterol assimilation, lactase activity, and vitamin production)
3A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
bacteria in an adult colon and up to 95% of
those found in breast-fed newborns.
10
Bifidobacteria produce vitamins, mainly of
the B group, as well as digestive enzymes,
such as casein phosphatase and lysozyme,
11
and metabolic end products such as acetate
and lactate that lower the pH in the local gut
environment making it unfavourable for
bacterial growth.
12
Fujiwara et al.
13
identified
a 1 000 000 kDa protein expressed by
bifidobacteria that may inhibit the adhesion
of pathogenic Escherichia coli.
Among the lactobacilli, Lactobacillus casei
GG (LGG) was originally selected as a
therapeutic agent because of its resistance to
gastric acid and bile digestion, as well as its
ability to colonize the human colon at least
for the duration of supplementation
10
The
lack of plasmids in lactobacilli also makes
them suitable for preventing the transfer of
antibiotic resistance. On the other hand,
lactobacilli inhibit the growth of other
bacterial species in vitro, such as Clostridium,
Bacteroides, Bifidobacterium, Pseudomonas,
Staphylococcus, Streptococcus and
Enterobacteriaceae.
14
This property may
depend on both hydrogen peroxide
production, which decreases intraluminal
pH and oxygen concentration, and
bacteriocin production
15
. L. acidophilus has
also been shown to inhibit growth of the
pathogenic bacteria Yersinea enterocolitica,
Bacillus cereus, E. coli, Listeria monocytogenes
and Salmonella.
16
Perdigon et al.
17
have
demonstrated that L. casei and L. acidophilus
enhance IgA production from plasma cells in
a dose-dependent manner. LGG increases
IgA production in rotavirus infections.
18
Exposure to lactobacilli also results in
increased expression of interleukin (IL)-12,
IL-6, tumour necrosis factor (TNF) mRNA
and increased cytokine excretion.
19,20
Many clinical trials have evaluated the
efficacy of probiotics in the therapy and
prevention of acute and chronic
gastrointestinal diseases, and also of non-
intestinal diseases such as atopy, respiratory
infections, vaginitis and hypercholesterol-
aemia. The evaluation of data on the
efficacy of probiotic microorganisms is often
TABLE 2:
Common microorganisms investigated for their probiotic properties
8
Lactobacilli
Lactobacillus acidophilus spp.; L. acidophilus LA-1
L. casei spp.; L. rhamnosus GG
L. reuteri
L. delbrueckii subsp. bulgaricus
L. plantarum spp.; L. plantarum 299 V
L. fermentum KLD
L. johnsonii
Bifidobacteria
Bifidobacterium bifidum
B. breve
B. infantis
B. longum
Other bacteria
Enterococcus faecium
Escherichia coli Nissle 1917
Streptococcus salivarius subsp. thermophilus
Yeast
Saccharomyces boulardii
4A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
controversial due to the use of different study
designs, the inclusion of different probiotic
species, the heterogeneous nature of the
study populations and varying outcome
measures. The dose of microorganism that is
administered can also vary greatly and there
is no uniform consensus on therapeutic
schedules. Studies to date have used oral
doses ranging from 1 10
9
to 10 10
9
colony-
forming units (cfu) per dose, with
administration frequency ranging from
twice daily to intermittent weekly schedules.
Based on the literature, the number of
probiotic microorganisms that is sufficient to
obtain temporary colonization is 10
9
live
cells daily for adults
21
and, according to this
meta-analysis, the dose might be crucial to
ensure efficacy, since a doseresponse
relationship has been observed for
lactobacilli administration in the therapy of
acute diarrhoea.
21
Probiotic supplements are generally
regarded as safe because the microorganisms
they contain are identical to those found in the
human gastrointestinal and vaginal
microflora. Nevertheless, probiotics as viable
microorganisms may have the potential to
cause invasive infections in hosts with
compromised mucosal epithelia.
22
Large-scale
epidemiological studies in countries where
probiotic use is endemic demonstrate low rates
of systemic infection of 0.05 0.40% in
adults.
22
Documented invasive infections have
been primarily noted in immunocompromised
adults.
23,24
Invasive infections attributed to
probiotic supplementation in infants and
children are exceedingly rare,
25
but children
with indwelling central venous catheter access,
prolonged hospitalizations, an immuno-
compromised status and a recognized or
potential impairment of gut mucosal
integrity seem to be particularly at risk.
Most probiotic formulations are
administered orally, either in capsule or
powder form. Furthermore, food processing
may result in varying viability and cfu
ability of the probiotic microorganisms,
compared with commercially-prepared
probiotic formulations. The purpose of this
clinical report is to review evidence on the
use of probiotics in a variety of
gastrointestinal and non-gastrointestinal
conditions. PubMed, MEDLINE and EMBASE
searches (January 1978 March 2007) were
performed in order to identify all human
trials related to probiotic therapy.
Acute and chronic
gastrointestinal disease
INFECTIOUS DIARRHOEA
Probiotics have been extensively studied in
the treatment and prevention of infectious
gastroenteritis, and show convincing
evidence that they reduce symptom duration
(Table 3),
26 52
especially in the paediatric
population.
53 56
Probiotics may, indeed,
reduce the duration of infectious diarrhoea
by 0.7 days, as well as the frequency of
diarrhoea.
21
More solid evidence of efficacy is
found in the treatment of mild-to-moderate
rotavirus diarrhoea that has been treated
early with oral rehydration therapy (ORT) in
association with LGG.
27,32,33,35
LGG reduces
the duration of rotavirus excretion
41
and, as
a consequence, it may limit viral diffusion.
Several trials have evaluated the efficacy of
probiotics in preventing community-
acquired and nosocomial infectious
diarrhoea with contrasting results.
26,51,57
Probiotics are not efficacious in non-
rotavirus gastroenteritis, especially entero-
invasive bacterial diarrhoea.
32,50
LGG
appears to be effective for viral but not
bacterial diarrhoea, possibly because of
LGG-associated over-expression of intestinal
mucins (MUC-2, MUC-3), which are
protective during intestinal infections. These
protective qualities could be overcome by
5A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
mucinase-producing bacteria.
58
A new
probiotic, Lactobacillus paracasei ST11,
appears to be able to ameliorate the
outcome of non-rotavirus diarrhoea.
52
Many studies have investigated the
efficacy of probiotics, alone or in
combination, in preventing travellers
bacterial diarrhoea in adults, with
contrasting results.
59 62
Whereas some trials
offer encouraging results, further studies are
needed to investigate the cost versus benefit
of treating all travellers.
ANTIBIOTIC-ASSOCIATED
DIARRHOEA
Antibiotic-associated diarrhoea (AAD) is
defined as an otherwise unexplained
diarrhoea occurring in association with
antibiotic administration. AAD occurs in 5
30% of the general population during
antibiotic treatment.
10
Although no infectious
agents are found in most cases, the bacterial
agent commonly associated with the most
severe episodes of AAD is Clostridium difficile.
Almost all antibiotics, particularly those
active against anaerobes, can cause
diarrhoea, but the risk seems to be higher with
aminopenicillins, the combination of
aminopenicillins and clavulanate,
cephalosporins, and clindamycin.
63
Preventive
measures include the use of probiotics, the
rationale for their use being based on the
assumption that, in some instances, diarrhoea
is associated with perturbations of the normal
composition of the intestinal microflora.
Recent meta-analyses have shown that
some probiotic strains are associated with a
decrease of AAD;
63 65
Saccharomyces boulardii
seems to be the most effective microorganism
although children with AAD have also been
found to benefit from LGG supplementation
(Table 4).
66 89
S. boulardii is a patented yeast
preparation that has been shown to inhibit
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GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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12A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
vivo and in vitro
10
It lives at an optimum
temperature of 37C and has been shown to
resist digestion and, therefore, can reach the
colon in a viable state. S. boulardii also
appears to be unaffected by antibiotic
therapy. Once therapy has been completed,
this microorganism is rapidly eliminated.
90
There is a risk of haematogenous diffusion in
immunocompromised patients.
91
S. boulardii
inhibits C. difficile toxins A and B by
releasing a 54 kDa protease that cleaves
these toxins and their receptors at the brush
border membrane, which might explain how
S. boulardii can inhibit recurrent episodes of
C. difficile infection.
92
A few trials have also
documented a lack of efficacy of probiotics in
preventing AAD.
86 89
INFLAMMATORY BOWEL DISEASE
Several mechanisms of action have been
elucidated for probiotics in the past few years
that relate to inflammatory bowel disease
and that support their use in the
management of clinical inflammatory
bowel disease. The potential use of probiotics
in the inflammatory bowel diseases, Crohns
disease, ulcerative colitis and pouchitis, has
been explored in a number of studies
(Table 5).
93 122
Crohns disease
An epidemiological study found that
Bifidobacterium counts were decreased in the
faeces of patients with Crohns disease.
123
Since antibiotics are widely used in its
treatment, probiotics have been suggested as
a new treatment. The immunomodulatory
effect of lactobacilli on cytokine production
could be beneficial in reducing the
characteristic inflammatory pattern of
Crohns disease. It is still unclear whether
probiotics are useful both for the treatment
of active Crohns disease as well as for
maintaining relapse rates.
93 99,109,110
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13A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
T
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L
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GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
Ulcerative colitis
A study of the intestinal microflora of IL-10
knockout mice revealed that, as colitis
developed between 2 and 8 weeks of age,
there was a decrease in the numbers of
lactobacilli.
124
Indeed, by repopulating the
mice with supplemental lactobacilli the
histological severity of the colitis was
attenuated and the amount of mucosal
adherence and invasion by aerobic bacteria
was decreased. Several studies have
evaluated the effects of probiotic treatment
in human ulcerative colitis.
100 108
Clinical
studies of affected patients have demonstrated
the efficacy of probiotics, most notably E. coli
(strain Nissle 1917), in maintaining remission
in ulcerative colitis at a rate equivalent to
treatment with mesalamine.
100,102,103
Pouchitis
Pouchitis, a common complication of ileal
pouch anal anastomosis (IPAA) surgery for
ulcerative colitis, is a non-specific
inflammatory disease of the ileal reservoir.
The clinical frequency of pouchitis varies
depending on the duration of the follow-up,
but it is approximately 50% after 10 years
125
Although the causes of pouchitis remain
largely unknown, some studies have
reported reduced counts of lactobacilli and
bifidobacteria within the pouch,
126
which
suggests that these bacteria may play a role
in the development of this syndrome.
Moreover, the majority of pouchitis cases
respond to treatment with antimicrobial
agents. The therapeutic potential of
probiotics for pouchitis has been studied in
several clinical trials.
111 122,125
There is strong evidence to support the use
of the probiotic cocktail VSL#3 (Lactobacillus
plantarum, L. acidophilus, L. delbrueckii subsp.
bulgaricus, L. casei, Bifidobacterium longum, B.
breve, B. infantis and Streptococcus salivarius
subsp. thermophilus) for both primary
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18A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
pouchitis prevention after IPAA surgery and
prevention of pouchitis recurrence after
antibiotic-induced remission; probiotic
supplementation is particularly suggested in
the post-operative period.
112,113,115,118,119
IRRITABLE BOWEL SYNDROME
Irritable bowel syndrome is the most
frequently diagnosed gastroenterological
disorder, affecting 11 14% of the North
American population
10
. It is characterized by
abdominal pain, flatulence and irregular
bowel movements. The aetiology of irritable
bowel syndrome is unclear, but may include
genetic susceptibility, behavioural and stress
factors.
127
Its causes have not been fully
elucidated, however the increased gas
production accompanying the syndrome is
suspected to result from a perturbed intestinal
microflora. More specifically, irritable bowel
syndrome has been associated with lower
lactobacilli and bifidobacteria colonies and
increased anaerobic Clostridium spp. in place
of anaerobic Bacteriodes spp. and
Bifidobacterium spp.
128
Clinical trials on patients with irritable
bowel syndrome have suggested that
supplementation with probiotics might be a
promising therapy. Although studies are not
easily comparable because of differences in
study design, probiotic dose, strain and
duration of therapy, the results suggest
amelioration of symptoms such as bloating,
abdominal pain or colonic transit
(Table 6).
129 147
HELICOBACTER PYLORI INFECTION
Helicobacter pylori is a highly prevalent
pathogen considered to be an aetiological
agent for gastroduodenal ulcers, and a risk
factor for gastric adenocarcinoma and
lymphoma in humans. It is one of the most
prevalent pathogens with over 50% of the
worlds population being colonized by this
microorganism. Gastric colonization by H.
pylori results in chronic gastritis, which is
asymptomatic in most subjects;
gastroduodenal symptoms and pathologies
develop in 10 15% of the infected
population.
148
The current treatment for H. pylori-
colonized symptomatic patients includes a
combination of antibiotics (amoxicillin,
clarythromicin, metronidazol) and a proton-
pump inhibitor (omeprazol, lanzoprazol,
pentoprazol). This treatment does not
eradicate H. pylori in all patients because of
antibiotic resistance and unsatisfactory
patient compliance due to adverse effects,
such as vomiting, diarrhoea, abdominal
pain and alterations in taste. The high cost
of the treatment also limits its adequate
application. In addition, children who need
to be treated tend to relapse more frequently
and rapidly than adults. In recent years,
therefore, alternative strategies to prevent or
decrease H. pylori colonization in high-risk
populations have been considered, including
probiotic supplementation.
148
The potential role of probiotics in
protecting against or reducing H. pylori
colonization is based on various modes of
action:
148
(i) a decrease in pathogenic
bacterial overgrowth; (ii) production of lactic
acid and short chain fatty acids that
decrease the pH dose-dependent inhibition
of H. pylori growth and has been observed
with acetic and lactic acid, the latter
demonstrating the strongest effect;
149
(iii)
production of bacteriocines with
antimicrobial activities; and (iv)
stabilization of the intestinal barrier
functions and reduction of mucosal
inflammation associated with increased
levels of prostaglandins.
Probiotics, particularly lactobacilli, have
been used to treat H. pylori infection both
alone and in combination with other agents
19A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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22A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
(Table 7).
150 173
Clinical trials in colonized
adults and children suggest that probiotics
do not eradicate H. pylori, but that they help
to maintain lower levels of this pathogen in
the stomach.
148
Combinations of antibiotics
and probiotics may increase eradication
rates and/or decrease adverse events.
148
NECROTIZING ENTEROCOLITIS
Although necrotizing enterocolitis accounts
for a great deal of morbidity and mortality
among premature infants, the mechanism of
injury is still not well understood. It is
hypothesized that the intestinal injury
results from synergy between the three major
risk factors, prematurity, enteral feeding and
bacterial colonization, leading to ischaemic
bowel necrosis.
174
In animal models, supplementation with
bifidobacteria and subsequent colonization
may significantly reduce the incidence of
necrotizing enterocolitis by inhibiting the
growth of necrotizing enterocolitis-associated
bacteria, such as clostridia.
175,176
Based on
the promising results of animal models,
some studies have evaluated the effects of
probiotic supplementation on the incidence
of necrotizing enterocolitis in newborns.
177 180
Although probiotics appear to be promising,
further studies in different settings are
needed to confirm these findings.
Allergy
Recently, diagnoses of autoimmune and
atopic diseases have dramatically increased.
The factors that may be involved in this are:
(i) reduced microbial stimulation during
infancy and early childhood which results in
slower postnatal maturation of the immune
system and development of an optimal
balance between T helper 1 (Th1)- and Th2-
like immunity (the hygiene hypothesis); and
(ii) an altered microflora that promotes the
persistence of those Th2 cytokines (IL-4, IL-5,
IL-13) that are predominant at birth and
prevents the shift towards a Th1 response
with IL-12 and interferon gamma
production. Several studies have shown that
the gut microflora is altered in atopic
children with a prevalence of clostridia,
supporting the latter hypothesis.
181,182
Since
the bowel is sterile at birth, diet may
influence the development and composition
of the intestinal microflora. Indeed, there are
clear differences in the microflora between
breast-fed and formula-fed infants.
183,184
Since probiotics are able to influence the
composition of the intestinal microflora
and may be able to promote the Th2/Th1
switch, several studies have evaluated their
efficacy in reducing the incidence of atopic
clinical symptoms with promising results
(Table 8).
185 206
Other clinical areas
The potential efficacy of probiotics has been
further evaluated in a range of clinical
applications (Table 9), for example bacterial
vaginosis, otitis media, cancer prevention
and hypercholesterolaemia.
207 266
UROGENITAL TRACT INFECTIONS
The dominant bacteria in the urogenital
tract of healthy women are lactobacilli.
During episodes of urinary tract and vaginal
infection, usually by faecal microorganisms,
the number of lactobacilli decreases and
antibiotics are usually the treatment of
choice.
267
Antibiotics, however, frequently
cause gastrointestinal symptoms, may raise
drug resistance and do not restore the
urogenital tracts natural barrier to infection.
Some recent studies suggest alternative
strategies for treatment and protection
against urogenital tract infections.
207,208,211
Some probiotics show characteristics that
make them potentially effective in the
urogenital tract, particularly their capacity
23A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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to adhere to uroepithelial cells, and to
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and biosurfactant secretion.
268,269
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viable conditions are able to reach the
vagina and urinary tract after enteral
colonization.
209 212,268
RESPIRATORY INFECTIONS
In a recent trial in formula-fed infants, LGG
administration demonstrated a mild but
significant role in preventing and reducing
respiratory infections and the severity of
otitis media in children.
238
Others have not
been able to confirm the efficacy of
probiotic use in the treatment of acute otitis
media.
215
CANCER PREVENTION
There are various hypothetical mechanisms
by which probiotics could exert an
anticancer effect, particularly in colon
cancer:
270
(i) they may bind to mutagenic
compounds and thus stimulate faecal or
urinary excretion of mutagens; (ii) they may
inhibit the ability of bad bacteria to convert
procarcinogens into carcinogens using
various enzymes such as glucuronidase,
nitroreductase, and cholylglycine hydrolase;
(iii) they may cause deactivation of
carcinogens by protecting DNA from
damage by bacterial invasion of intestinal
stem cells; and (iv) they may stimulate
immune surveillance and suppress
inflammatory processes. Nevertheless, the
clinical evidence for probiotic use in cancer
prevention is definitely insufficient.
216
CHOLESTEROL LEVEL
MODIFICATION
Animal models have shown the possibility of
decreasing total cholesterol levels by
probiotic supplementation and that this
probably occurs by reduced hepatic synthesis
33A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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42A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
and a parallel increase in cholesterol
conversion to bile acids.
10
Human studies,
however, have shown conflicting results.
217 222
Conclusion
Probiotics represent a new frontier for the
treatment of several gastrointestinal
disorders. Further research is needed,
however, to define the role of probiotics as
alternative or complementary therapies in
some intestinal and non-gastrointestinal
clinical applications. Guidelines on the use
of probiotics in various clinical settings
(Table 10)
271
need to be updated periodically
in order for the latest data to be included in
clinical applications.
Conflicts of interest
No conflicts of interest were declared in
relation to this paper.
TABLE 10:
Guidelines for probiotic use
271
Clinical
Clinical condition effectiveness
a
Probiotic microorganisms
Diarrhoea A Saccharomyces boulardii
43,47 49
Lactobacillus casei GG
26,27,32,33*,34,35,37*
L. reuteri ( L. rhamnosus)
30,31*,36*,38
Antibiotic-associated A S. boulardii
67,68,70,71,80,81*
, LGG
66,69,82*
diarrhoea Lactobacilli + bifidobacteria
77*,79*,84,85
Crohns disease B Lactobacillus casei GG
95*,97,99*
Ulcerative colitis A Escherichia coli (Nissle)
100,102,103
C Bifidobacteria
101*,105*,106*
Pouchitis A VSL#3
b112*,113*,115*,118*,119*
B Lactobacilli
114*,120*,121,122
Irritable bowel B Lactobacilli bifidobacteria
130,131*,132,133*,134*,137*,138,139,141,143,144
syndrome
Helicobacter pylori C Lactobacilli
154,156,157,164,165,167,168*
infection
Allergy B Lactobacillus casei GG
187*,188,192,197,198*,201
, other lactobacilli
185,202,204,205
C Bifidobacteria
191*,199*
*A very small number of subjects studied.
a
Clinical effectiveness is based on evidence obtained from at least one properly designed randomized controlled study: A,
recommendation based on strong positive controlled studies in the literature; B, recommendation based on positive controlled studies,
but the presence of some negative studies; C, recommendation based on some positive studies, but clearly an inadequate amount of
work to establish certainty.
b
VSL#3 comprises a mixture of Lactobacillus acidophilus, L. delbrueckii, L. casei, L. plantarum, Bifidobacterium breve, B. longum, B. infantis
and Streptococcus salivarius subsp. thermophilus.
Received for publication 2 July 2007 Accepted subject to revision 12 July 2007
Revised accepted 11 September 2007
Copyright 2007 Field House Publishing LLP
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52A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
53A
GV Zuccotti, F Meneghin, C Raimondi et al.
Probiotics in clinical practice
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Authors address for correspondence
Professor Gian Vincento Zuccotti
Department of Paediatrics, Luigi Sacco Hospital, University of Milan, Via GB Grassi 74,
20157 Milan, Italy.
E-mail: gianvincenzo.zuccotti@unimi.it