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The Journal of International Medical Research2008; 36: (Suppl 1): 1A 53A

1A

Probiotics in Clinical Practice: an

Overview

GV ZUCCOTTI1, F MENEGHIN1, C RAIMONDI 1, D D ILILLO1, C AGOSTONI 2, E RIVA2AND M G IOVANNINI 2

1Department of Paediatrics, Luigi Sacco Hospital, and 2Department of Paediatrics, SanPaolo Hospital, University of Milan, Milan, Italy

The observation that intestinal bacterial

microflora might be able to influenceimmune system surveillance throughchanged nutritional habits has raisedawareness of the role of probiotics. Theseare live microorganisms that are able toreach the gastrointestinal tract and alterits microfloral composition, producingbeneficial health effects when consumedin adequate amounts. Recent clinical

trials have evaluated the clinicaleffectiveness of probiotics in the treatmentand prevention of a wide range of acuteand chronic gastrointestinal diseases, andalso non-gastrointestinal diseases, such as

atopy, respiratory infections, vaginitis

and hypercholesterolaemia. Probioticsupplements are generally regarded assafe because the microorganisms theycontain are identical to those found inhuman gastrointestinal and vaginalmicroflora. Guidelines on the use of probiotics in the clinical setting requireperiodical updates for the latest data tobe included in clinical applications.

The purpose of this clinical report isto review current evidence on theuse of probiotics in a variety of gastrointestinal and non-gastrointestinalconditions.

KEY WORDS: P ROBIOTICS ; GASTROINTESTINAL DISEASES ; ALLERGY; INFECTIONS ; CLINICAL TRIALS ;EVIDENCE LEVEL ; CLINICAL EFFECTIVENESS

IntroductionThe intestinal mucosa has a huge surfacearea that is constantly exposed to antigenicstimulation. For this reason, thegastrointestinal tract has the most extensivelymphoid system of the human body, knownas gastrointestinal-associated lymphoidtissue (GALT), which has defence andimmune modulatory functions.

The main role of the gastrointestinalsystem is to transform food into simpler components that can be absorbed and usedto produce energy for cellular function and

growth. Specific immunological and non-immunological protective mechanismsprevent the transit of external andunprocessed antigens across thegastrointestinal barrier. These mechanismsare collectively known as the intestinalmucosal barrier, characterized by non-specific (non-immunological) defensivemechanisms such as intestinal motility,

mucus secretion, gastric acids and pancreaticenzymes, and specific (immunological)mechanisms such as immunoglobulin A(IgA) production and antigenGALT


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GV Zuccotti, F Meneghin, C Raimondi et al .Probiotics in clinical practice

interactions. 1 A fundamental entericfunction, known as oral tolerance, is basedon the interaction between the intestinalepithelium, GALT and food antigens, andconsists of a specific immunologicalhyporesponsivity to mucosal antigenexposure. 2 Oral tolerance, which starts inearly childhood, is able to suppress theimmune responses against both foodproteins and the hosts own residentintestinal bacterial microflora. The intestinalmicroflora is able to modulate thegastrointestinal immune system towardsoral tolerance and protect the gut frompathogenic microorganisms bycompetitively excluding them from nutrientsand epithelial attachment sites (oftenreceptors), by producing antimicrobialsubstances (bacteriocines) and by enhancingspecific antibody 3 production, while theneuroendocrine cells increasingly activateintestinal peristalsis. 4

The observation that intestinal bacterialmicroflora might be able to influenceimmune system surveillance throughchanged nutritional habits has focusedscientific attention on the role of thosebacterial strains known as probiotics.Probiotics, which means for life, are definedas live microorganisms that are able to reach

the gastrointestinal tract and alter itsmicrofloral composition, producing beneficialhealth effects on the host when consumed inadequate amounts. 5 Although the termprobiotic was first used in the 1960s tocontrast with the term antibiotic, reports onthe health benefits of bacteria in food can befound in the literature from earlier years. In1908 Metchnikoff 6 suggested that thelongevity of Bulgarian peasants could berelated to their large consumption of sour milk containing Lactobacillus bulgaricus .

Many microorganisms that constitute theanaerobic intestinal microflora could beconsidered as potential probiotics, but only afew are able to satisfy specific criteria thatdefine probiotics (T able 1). 7 A variety of probiotic microorganisms have been studiedas either single agents or combinationtherapies. Most bacterial strains withprobiotic activity belong primarily to twogenera, Lactobacillus and Bifidobacterium(Table 2). 8 According to the scientificliterature, the taxonomic identity, mainphenotypic features, safety and efficacy,should be clearly defined for any probioticmicroorganism. 9

The Bifidobacterium spp. represent a major group of saccharolytic bacteria in the largeintestine. 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)


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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 acetateand lactate that lower the pH in the local gutenvironment making it unfavourable for bacterial growth. 12 Fujiwara et al .13 identifieda 1 000 000 kDa protein expressed bybifidobacteria that may inhibit the adhesionof pathogenic Escherichia coli .

Among the lactobacilli, Lactobacillus caseiGG (LGG) was originally selected as atherapeutic agent because of its resistance togastric acid and bile digestion, as well as itsability to colonize the human colon at leastfor the duration of supplementation 10 Thelack of plasmids in lactobacilli also makesthem 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 maydepend on both hydrogen peroxideproduction, which decreases intraluminalpH and oxygen concentration, andbacteriocin production 15 . L. acidophilus hasalso been shown to inhibit growth of thepathogenic bacteria Yersinea enterocolitica ,Bacillus cereus , E. coli, Listeria monocytogenes and Salmonella .16 Perdigon et al. 17 havedemonstrated that L. casei and L. acidophilus enhance IgA production from plasma cells ina dose-dependent manner. LGG increases

IgA production in rotavirus infections. 18Exposure to lactobacilli also results in

increased expression of interleukin (IL)-12,IL-6, tumour necrosis factor (TNF) mRNAand increased cytokine excretion. 19,20

Many clinical trials have evaluated theefficacy of probiotics in the therapy andprevention of acute and chronicgastrointestinal diseases, and also of non-

intestinal diseases such as atopy, respiratoryinfections, vaginitis and hypercholesterol-aemia. The evaluation of data on theefficacy of probiotic microorganisms is often

TABLE 2:Common microorganisms investigated for their probiotic properties 8

LactobacilliLactobacillus acidophilus spp. ; L. acidophilus LA-1L. casei spp. ; L. rhamnosus GGL. reuteri L. delbrueckii subsp. bulgaricus L. plantarum spp. ; L. plantarum 299 V L. fermentum KLDL. johnsonii

BifidobacteriaBifidobacterium bifidumB. breve B. infantis B. longum

Other bacteriaEnterococcus faeciumEscherichia coli Nissle 1917Streptococcus salivarius subsp. thermophilus

YeastSaccharomyces boulardii


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controversial due to the use of different studydesigns, the inclusion of different probioticspecies, the heterogeneous nature of thestudy populations and varying outcomemeasures. The dose of microorganism that isadministered can also vary greatly and thereis no uniform consensus on therapeuticschedules. Studies to date have used oraldoses ranging from 1 10 9 to 10 10 9 colony-forming units (cfu) per dose, withadministration frequency ranging fromtwice daily to intermittent weekly schedules.Based on the literature, the number of probiotic microorganisms that is sufficient toobtain temporary colonization is 10 9 livecells daily for adults 21 and, according to thismeta-analysis, the dose might be crucial toensure efficacy, since a doseresponserelationship has been observed for lactobacilli administration in the therapy of acute diarrhoea. 21

Probiotic supplements are generallyregarded as safe because the microorganismsthey contain are identical to those found in thehuman gastrointestinal and vaginalmicroflora. Nevertheless, probiotics as viablemicroorganisms may have the potential tocause invasive infections in hosts withcompromised mucosal epithelia. 22 Large-scaleepidemiological studies in countries whereprobiotic use is endemic demonstrate low rates

of systemic infection of 0.05 0.40% inadults. 22 Documented invasive infections havebeen primarily noted in immunocompromisedadults. 23,24 Invasive infections attributed toprobiotic supplementation in infants andchildren are exceedingly rare, 25 but childrenwith indwelling central venous catheter access,prolonged hospitalizations, an immuno-compromised status and a recognized or

potential impairment of gut mucosalintegrity seem to be particularly at risk.

Most probiotic formulations areadministered orally, either in capsule or

powder form. Furthermore, food processingmay result in varying viability and cfuability of the probiotic microorganisms,compared with commercially-preparedprobiotic formulations. The purpose of thisclinical report is to review evidence on theuse of probiotics in a variety of gastrointestinal and non-gastrointestinalconditions. PubMed, MEDLINE and EMBASEsearches (January 1978 March 2007) wereperformed in order to identify all humantrials related to probiotic therapy.

Acute and chronicgastrointestinal diseaseINFECTIOUS DIARRHOEAProbiotics have been extensively studied inthe treatment and prevention of infectiousgastroenteritis, and show convincingevidence that they reduce symptom duration(Table 3), 26 52 especially in the paediatricpopulation. 53 56 Probiotics may, indeed,reduce the duration of infectious diarrhoeaby 0.7 days, as well as the frequency of diarrhoea. 21 More solid evidence of efficacy isfound in the treatment of mild-to-moderaterotavirus diarrhoea that has been treatedearly with oral rehydration therapy (ORT) inassociation with LGG. 27,32,33,35 LGG reducesthe duration of rotavirus excretion 41 and, asa consequence, it may limit viral diffusion.

Several trials have evaluated the efficacy of probiotics in preventing community-acquired and nosocomial infectiousdiarrhoea with contrasting results. 26,51,57

Probiotics are not efficacious in non-rotavirus gastroenteritis, especially entero-invasive bacterial diarrhoea. 32,50 LGGappears to be effective for viral but notbacterial diarrhoea, possibly because of

LGG-associated over-expression of intestinalmucins (MUC-2, MUC-3), which areprotective during intestinal infections. Theseprotective qualities could be overcome by


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T A B L E 3

( c o n t i n u e d ) :

T y p e o f

R e f e r e n c e

T y p e o f t r i a l

P o p u

l a t i o n s t u d i e d

T y p e o f p r o b i o t i c

P r o b i o t i c d o s e

O u t c o m e

e v i d e n c e

a

I s o l a u r i e t a

l . ,

R a n d o m i z e d ,

7 1 w e l l - n o u r i s h e d c h i l d r e n a g e d

L a c t o b a c

i l l u s s p s t r a i n

A f t e r O R T

, g r o u p 1 r e c e i v e L G G i n e i t h e r f o r m w a s e f f e c t i v e i n

I

1 9 9 1 3 4

p l a c e b o -

4

4 5 m o n t h s

G G ( L G G )

L G G f e r m e n t e d m i l k

s h o r t e n i n g t h e c o u r s e o f a c u t e d i a r r h o e a

c o n t r o l l e d

p r o d u c t 1 2 5 g ( 1 0 1 0

1 0 1 1 c f u ) t w i c e d a i l y

, g r o u p

2 L G G f r e e z e - d r i e d p o w d e r

o n e d o s e ( 1 0 1 0

1 0 1 1 c f u ) ,

g r o u p 3 p l a c e b o ( 1 2 5 g

p a s t e u r i z e d y o g u r t ) t w i c e

d a i l y f o r 5 d a y s

S z y m a n s k i


8 7 c h i l d r e n ( 2 m o n t h s

6 y e a r s )

L a c t o b a c

i l l u s r h a m n o s u s

L G G d o s e o f 1 . 2 x 1 0 1 0

A d m i n i s t r a t i o n o f

L . r h a m n o s u s s t r a i n s

I

e t a l . ,

2 0 0 6 3 5

d o u b l e - b

l i n d ,

w i t h i n f e c t i o u s d i a r r h o e a

G G ( L G G )

c f u t w i c e d a i l y f o r 5 d a y s

s h o r t e n e d d u r a t i o n o f r o t a v i r u s d i a r r h o e a

i n

p l a c e b o -

c h i l d r e n b u t n o t o f d i a r r h o e a o f a n y a e t i o l o g y

c o n t r o l l e d

R o s e n f e l d t


2 4 n o n - h o s p i t a l i z e d c h i l d r e n

L a c t o b a c


1 0 1 0 c f u t w i c e d a i l y

C o m b i n a t i o n o f

L . r h a m n o s u s a n d L . r e u t e r

i

I

e t a l . ,

2 0 0 2 3 6

p l a c e b o -

w i t h m i l d d i a r r h o e a

1 9 0 7 0 - 2 L . r e u t e r i D

S M

f o r 5 d a y s

w a s e f f e c t i v e i n r e d u c i n g d u r a t i o n o f

c o n t r o l l e d

1 2 2 4 6

d i a r r h o e a

P a n t e t a l . ,

P r o s p e c t i v e ,

3 9 c h i l d r e n ( m e a n a g e 8

L a c t o b a c

i l l u s

G G ( L G G )

W i t h r e h y d r a t i o n 2 0

L G G a c c e l e r a t e d r e c o v e r y f r o m a c u t e w a t e r y

I

1 9 9 6 3 7

p l a c e b o -

m o n t h s ) h o s p i t a l i z e d f o r

c h i l d r e n r e c e i v e d o r a l L G G d i a r r h o e a i n c h i l d r e n i n t r o p i c a l s e t t i n g

c o n t r o l l e d ,

a c u t e d i a r r h o e a

a s a f r e e z e - d r i e d p r e p a r a t i o n ,

t r i p l e - b

l i n d

t w i c e d a i l y f o r 2 d a y s

R o s e n f e l d t


6 9 c h i l d r e n h o s p i t a l i z e d f o r

L a c t o b a c


M i x t u r e o f

L . r h a m n o s u s

T h e t w o p r o b i o t i c s a m e l i o r a t e d a c u t e

I

e t a l . ,

2 0 0 2 3 8

p l a c e b o -

a c u t e d i a r r h o e a

1 9 0 7 0 - 2 , L . r e u t e r i

D S M

a n d L . r e u t e r

i ( 1 0 1 0 c f u )

d i a r r h o e a i n h o s p i t a l i z e d c h i l d r e n a n d

c o n t r o l l e d

1 2 2 4 6

t w i c e d a i l y f o r 5 d a y s

r e d

u c e d p e r i o d o f r o t a v i r u s e x c r e t i o n

M a j a m a a

D o u b l e - b l i n d

4 9 c h i l d r e n ( 6

3 5 m o n t h s )

L a c t o b a c

i l l u s

G G ( L G G ) ,

1 6 r e c e i v e d L G G ( 6

. 2 5 x

C e r t a i n s t r a i n s o f l a c t i c a c i d b a c t e r i a

,

I I

e t a l . ,

1 9 9 5 3 9

w i t h r o t a v i r u s g a s t r o e n t e r i t i s

S t r e p t o c o c c u s

1 0 9 c f u ) , 1

4 r e c e i v e d

p a r t i c u l a r l y L G G

, p r o m o t e d s e r u m a n d

t h e r m o p

h i l u s ,

L .

L . r h a m n o s u s

( 2 . 7

5 x 1 0 8

i n t e s t i n a l i m m u n e r e s p o n s e s t o r o t a v i r u s

d e l b r u c k

i i s u b s p .

c f u ) a n d 1 9 r e c e i v e d

b u l g a r

i c u s

L . r h a m n o s u s +

L . d e l b r u c k

i i

+ L . b u l g a r

i c u s

( 3 . 5

x 1 0 9

c f u ) t w i c e d a i l y f o r 5 d a y s

L e e e t a l . ,

P r o s p e c t i v e

1 0 0 c h i l d r e n ( 6

6 0 m o n t h s )

L a c t o b a c

i l l u s a c

i d o p

h i l u s ,

5 0 c h i l d r e n g i v e n

T h e s e p r o b i o t i c s w e r e a n e f f e c t i v e a d j u v a n t

I I

2 0 0 1 4 0

h o s p i t a l i z e d w i t h a c u t e d i a r r h o e a

B i f i d o b a c t e r i u m

i n f a n t

i s

L . a c

i d o p

h i l u s a n d

t h e r a p y i n r o t a v i r u s - p o s i t i v e a n d - n e g a t i v e

B . i n f a n t

i s ( 1 0 9 v i a b l e c e l l s

c h i l d r e n w i t h d i a r r h o e a a n d c a n s a f e l y b e

o f e a c h ) , o n e c a p s u l e t h r e e a d m i n i s t e r e d d u r i n g a n e p i s o d e o f a c u t e

t i m e s d a i l y f o r 4 d a y s

d i a r r h o e a


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mucinase-producing bacteria. 58 A newprobiotic, Lactobacillus paracasei ST11,appears to be able to ameliorate theoutcome of non-rotavirus diarrhoea. 52

Many studies have investigated theefficacy of probiotics, alone or incombination, in preventing travellersbacterial diarrhoea in adults, withcontrasting results. 59 62 Whereas some trialsoffer encouraging results, further studies areneeded to investigate the cost versus benefitof treating all travellers.

ANTIBIOTIC-ASSOCIATEDDIARRHOEAAntibiotic-associated diarrhoea (AAD) isdefined as an otherwise unexplaineddiarrhoea occurring in association withantibiotic administration. AAD occurs in 5 30% of the general population duringantibiotic treatment. 10 Although no infectiousagents are found in most cases, the bacterialagent commonly associated with the mostsevere episodes of AAD is Clostridium difficile.Almost all antibiotics, particularly thoseactive against anaerobes, can causediarrhoea, but the risk seems to be higher withaminopenicillins, the combination of aminopenicillins and clavulanate,cephalosporins, and clindamycin. 63 Preventivemeasures include the use of probiotics, the

rationale for their use being based on theassumption that, in some instances, diarrhoeais associated with perturbations of the normalcomposition of the intestinal microflora.

Recent meta-analyses have shown thatsome probiotic strains are associated with adecrease of AAD; 63 65 Saccharomyces boulardiiseems to be the most effective microorganismalthough children with AAD have also been

found to benefit from LGG supplementation(T able 4). 66 89 S. boulardii is a patented yeastpreparation that has been shown to inhibitthe growth of pathogenic bacteria both in

T A B L E 3

( c o n t i n u e d ) :

T y p e o f

R e f e r e n c e


P o p u




O u t c o m e

e v i d e n c e

a

S a l a z a r - L i n d o

,


M a l e i n f a n t s a g e d 3

3 6 m o n t h s

L a c t o b a c

i l l u s c a s e

i s t r a i n

M i l k f o r m u l a w i t h

N o

s i g n i f i c a n t d i f f e r e n c e b e t w e e n t h e t w o

I

e t a l . ,

2 0 0 4 5 0

d o u b l e - b

l i n d

w i t h a c u t e w a t e r y d i a r r h o e a ;

G G ( L G G )

1 0 9 c f u / m l o f L G G

g r o u p s ( p l a c e b o v s L G G ) . N o p o s i t i v e

8 9 r e c e i v e d p l a c e b o

, 9 0 L G G

.

e f f e c t s o f L G G

C o s t a - R

i b e i r o


1 2 4 m a l e c h i l d r e n < 2 y e a r s o l d

L a c t o b a c

i l l u s

G G ( L G G )

O R S w i t h p l a c e b o a n d

N o

s i g n i f i c a n t r e d u c t i o n i n d i a r r h o e a

I

e t a l . ,

2 0 0 3 5 1

d o u b l e - b

l i n d ,

w i t h m o d e r a t e d e h y d r a t i o n

w i t h L G G

d u r a t i o n a n d s t o o l o u t p u t

p l a c e b o -

c o n t r o l l e d

S a r k e r e t a

l . ,


2 3 0 m a l e i n f a n t s a n d y o u n g

L a c t o b a c

i l l u s p a r a c a s e

i

1 0 1 0 c f u l y o p h i l i z e d S T 1 1

S T 1 1 h a d a c l i n i c a l l y s i g n i f i c a n t b e n e f i t i n

t h e

I

2 0 0 5 5 2

d o u b l e - b

l i n d ,

c h i l d r e n ( 4 2 4

m o n t h s ) w i t h

s t r a i n S T 1 1

d a i l y f o r 5 d a y s

m a n a g e m e n t o f c h i l d r e n w i t h n o n - r o t a v i r u s -

p l a c e b o -

d i a r r h o e a o f < 2 d a y s d u r a t i o n ;

i n d u c e d d i a r r h o e a , b u t w a s i n e f f e c t i v e i n

c o n t r o l l e d

h o s p i t a l i z e d

t h o s e w i t h r o t a v i r u s d i a r r h o e a

c f u , c o l o n y f o r m i n g u n i t s ; O R T

, o r a l r e h y d r a t i o n t h e r a p y ; I g A

, i m m u n o g l o b u l i n A

.

a T y p e o f e v i d e n c e : I , f r o m a t l e a s t o n e p r o p e r l y d e s i g n e d r a n d o m i z e d c o n t r o l l e d s t u d y ; I I , f r o m

w e l l - d e s i g n e d c o h o r t o r c a s e - c o n t r o l l e d t r i a l s w i t h o u t r a n d o m i z a t i o n .


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T A B L E 4

:

C l i n i c a l t r i a l s o f t h e e f f i c a c y o f p r o b i o t i c s f o r t h e t r e a t m e n t a n d

p r e v e n t i o n o f a n t i b i o t i c - a s s o c i a t e d d i a r r h o e a 6

6

8 9

T y p e o f

R e f e r e n c e


P o p u




O u t c o m e

e v i d e n c e

a

A r v o l a e t a

l . ,


1 6 7 ( f i n a l s t u d y

p o p u l a t i o n : 1 1 9 ) L a c t o b a c


2 x 1 0 1 0 c f u L G G i n

L G G e f f e c t i v e l y p r e v e n t e d d i a r r h o e a i n

I

1 9 9 9 6 6

d o u b l e - b

l i n d ,

c h i l d r e n ( a g e d 2 w e e k s

1 2 . 8

G G ( L G G )

c a p s u l e s t w i c e d a i l y

c h i l d r e n r e c e i v i n g a n t i m i c r o b i a l

p l a c e b o -

y e a r s ) o n a n t i b i o t i c t h e r a p y f o r

t r e a t m e n t f o r r e s p i r a t o r y i n f e c t i o n s

c o n t r o l l e d

a c u t e r e s p i r a t o r y i n f e c t i o n s

K o t o w s k a e t a l . ,


2 6 9 c h i l d r e n ( 6

m o n t h s

1 4

S a c c

h a r o m y c e s

b o u

l a r d

i i

2 5 0 m g

S . b o u l a r

d i i o r a l l y

S . b o u l a r

d i i e f f e c t i v e l y r e d u c e d t h e r i s k o f

I

2 0 0 5 6 7

d o u b l e - b

l i n d ,

y e a r s o l d ) w i t h o t i t i s m e d i a a n d / o r

t w i c e d a i l y

A A D i n c h i l d r e n

p l a c e b o -

r e s p i r a t o r y t r a c t i n f e c t i o n s

c o n t r o l l e d

C a n e t a l . ,


1 5 1 p a t i e n t s ( 2 5

5 0 y e a r s o l d ) S a c c

h a r o m y c e s

b o u

l a r d

i i

S . b o u l a r

d i i t w i c e d a i l y

P r o p h y l a c t i c u s e o f

S . b o u l a r

d i i r e d u c e d

I

2 0 0 6 6 8

d o u b l e - b

l i n d ,

h o s p i t a l i z e d a t a D e p a r t m e n t

A A D i n h o s p i t a l i z e d p a t i e n t s

c o n t r o l l e d

o f I n f e c t i o u s D i s e a s e a n d C l i n i c a l

M i c r o b i o l o g y

V a n d e r h o o f


2 0 2 c h i l d r e n ( 6

m o n t h s

1 0

L a c t o b a c

i l l u s c a s e

i s p .

L G G ( 1 x 1 0 1 0

L G G r e d u c e d i n c i d e n c e o f A A D i n

I

e t a l . ,

1 9 9 9 6 9

d o u b l e - b

l i n d

y e a r s o l d )

, 1 8 8 c o m p l e t e d t h e

r h a m n o s u s

2 x 1 0 1 0 c f u / d a y )

c h i l d r e n t r e a t e d w i t h o r a l a n t i b i o t i c s

s t u d y , r e c e i v i n g

o r a l a n t i b i o t i c

f o r c o m m o n c h i l d h o o d i n f e c t i o n s

t h e r a p y i n a n o u t p a t i e n t s e t t i n g

M c F a r l a n d


1 9 3 h o s p i t a l i z e d p a t i e n t s

S a c c

h a r o m y c e s

b o u

l a r d

i i

L y o p h i l i z e d

S . b o u l a r

d i i

P r o p h y l a c t i c u s e o f

S . b o u l a r

d i i w i t h a

I

e t a l . ,

1 9 9 5 7 0

d o u b l e - b

l i n d ,

r e c e i v i n g

- l a c t a m a n t i b i o t i c s

( 1 g / d a y ) w i t h i n 7 2 h o f

- l a c t a m a n t i b i o t i c g a v e s i g n i f i c a n t r e d u c t i o n

p l a c e b o -

t h e s t a r t o f a n t i b i o t i c

o f A A D w i t h n o s e r i o u s a d v e r s e r e a c t i o n s

c o n t r o l l e d ,

t r e a t m e n t a n d c o n t i n u e d

p a r a l l e l - g r o u p

u n t i l 3 d a y s a f t e r a n t i b i o t i c

d i s c o n t i n u e d

S u r a w i c z


1 8 0 h o s p i t a l i z e d p a t i e n t s

S a c c

h a r o m y c e s

b o u

l a r d

i i

S . b o u l a r

d i i g i v e n i n c a p s u l e

S . b o u l a r

d i i r e d u c e d t h e i n c i d e n c e o f

I

e t a l . ,

1 9 8 9 7 1

r a n d o m i z e d ,

r e c e i v i n g a n t i m i c r o b i a l t r e a t m e n t

f o r m c o n c u r r e n t l y w i t h

a n t i b i o t i c - a s s o c i a t e d d i a r r h o e a i n

d o u b l e - b

l i n d ,

a n t i b i o t i c s

h o s p i t a l i z e d p a t i e n t s

c o n t r o l l e d

C o r r e a e t a

l . ,


8 0 i n f a n t s ( a g e d 6

3 6 m o n t h s )


l a c t i s

,

C o m m e r c i a l f o r m u l a

P r e v e n t i o n o f A A D i n i n f a n t s w a s o b t a i n e d

I

2 0 0 5 7 2

d o u b l e - b

l i n d ,

S t r e p t o c o c c u s

c o n t a i n i n g 1 0 7 v i a b l e c e l l s b y o r a l t r e a t m e n t w i t h a d a i l y d o s e o f t h e s e

c o n t r o l l e d

t h e r m o p

h i l u s

o f B . l a c t

i s a n d 1 0 6 v i a b l e

t w o p r o b i o t i c s

f o r m u l a s t u d y

c e l l s o f

S . t h e r m o p

h i l u s

a t i n i t i a t i o n o f a n t i b i o t i c s

f o r 1 5 d a y s


10/53


11/53


12/53

12A


vivo and in vitro10 It lives at an optimumtemperature of 37C and has been shown toresist digestion and, therefore, can reach thecolon in a viable state. S. boulardii alsoappears to be unaffected by antibiotictherapy. Once therapy has been completed,this microorganism is rapidly eliminated. 90

There is a risk of haematogenous diffusion inimmunocompromised patients. 91 S. boulardiiinhibits C. difficile toxins A and B byreleasing a 54 kDa protease that cleavesthese toxins and their receptors at the brushborder membrane, which might explain howS. boulardii can inhibit recurrent episodes of C. difficile infection. 92 A few trials have alsodocumented a lack of efficacy of probiotics inpreventing AAD. 86 89

INFLAMMATORY BOWEL DISEASESeveral mechanisms of action have beenelucidated for probiotics in the past few yearsthat relate to inflammatory bowel diseaseand that support their use in themanagement of clinical inflammatorybowel disease. The potential use of probioticsin the inflammatory bowel diseases, Crohnsdisease, ulcerative colitis and pouchitis, hasbeen explored in a number of studies(Table 5). 93 122

Crohns disease

An epidemiological study found thatBifidobacterium counts were decreased in thefaeces of patients with Crohns disease. 123

Since antibiotics are widely used in itstreatment, probiotics have been suggested asa new treatment. The immunomodulatoryeffect of lactobacilli on cytokine productioncould be beneficial in reducing thecharacteristic inflammatory pattern of

Crohns disease. It is still unclear whether probiotics are useful both for the treatmentof active Crohns disease as well as for maintaining relapse rates. 93 99,109,110

T A B L E 4

( c o n t i n u e d ) :

T y p e o f

R e f e r e n c e


P o p u




O u t c o m e

e v i d e n c e a

L a w r e n c e


1 5 a d u l t s p r e s e n t i n g w i t h

L a c t o b a c


P a r t i c i p a n t s r a n d o m i z e d t o N o

d i f f e r e n c e i n o u t c o m e s

I

e t a l . ,

2 0 0 5 8 8

d o u b l e - b

l i n d ,

d i a r r h o e a , e n z y m e i m m u n o -

G G ( L G G )

o n e L G G c a p s u l e ( 4 0 m g

p l a c e b o -

a s s a y d e t e c t i o n o f s t o o l

l y o p h i l i z e d L G G a n d

c o n t r o l l e d

C l o s t r i d

i u m

d i f f i c i

l e t o x i n A o r

3 2 0 m g i n u l i n ) o r a l l y t w i c e

B , a n d h i s t o r y o f C

. d i f f i c i

l e

d a i l y

, a d j u n c t i v e l y w i t h

i n f e c t i o n i n t h e p r e c e d i n g y e a r

a n t i - C

. d i f f i c i

l e a n t i b i o t i c s ,

f o r d u r a t i o n o f a n t i b i o t i c

t h e r a p y a n d f o r a n

a d d i t i o n a l 2 1 d a y s

L e w i s e t a l . ,


6 9 p a t i e n t s ( > 6 5 y e a r s o l d )

S a c c

h a r o m y c e s

b o u

l a r d

i i

S . b o u l a r

d i i 1 1 3 g t w i c e

N o

e v i d e n c e t h a t c o n c o m i t a n t u s e o f

I

1 9 9 8 8 9

d o u b l e - b

l i n d ,

a d m i t t e d t o m e d i c a l w a r d s

d a i l y

S . b o u l a r

d i i w i t h a n t i b i o t i c s a l t e r e d t h e

p l a c e b o -

a n d w h o w e r e b e i n g

p a t i e n t s b o w e l h a b i t s o r p r e v e n t e d

c o n t r o l l e d

p r e s c r i b e d a n t i b i o t i c s

a p p e a r a n c e o f

C .

d i f f i c i

l e t o x i n i n s t o o l s

c f u , c o l o n y f o r m i n g u n i t s ; A A D

, a n t i b i o t i c - a s s o c i a t e d d i a r r h o e a .

a T y p e o f e v i d e n c e : I , f r o m a t l e a s t o n e p r o p e r l y d e s i g n e d r a n d o m i z e d c o n t r o l l e d s t u d y .


13/53

13A


T A B L E 5

:

C l i n i c a l t r i a l s o f t h e e f f i c a c y o f p r o b i o t i c s f o r t h e t r e a t m e n t a n d

p r e v e n t i o n o f i n f l a m m a t o r y

b o w e l d i s e a s e 9

3

1 2 2

T y p e o f

R e f e r e n c e


P o p u




O u t c o m e

e v i d e n c e

a

M a r t e a u e t a l . ,


9 8 p a t i e n t s w i t h C r o h n s d i s e a s e

L a c t o b a c

i l l u s

j o h n s o n i

i

T w o p a c k e t s p e r d a y

T h e p r o b i o t i c d i d n o t h a v e s u f f i c i e n t

I

2 0 0 6 9 3

d o u b l e - b

l i n d ,

w e r e e n r o l l e d

L A - 1

o f 2 x 1 0 9 c f u f o r 6 m o n t h s e f f e c t t o p r e v e n t e n d o s c o p i c r e c u r r e n c e o f

p l a c e b o -

C r o h n s d i s e a s e

c o n t r o l l e d

G u s l a n d i e t a l . ,

P l a c e b o -

3 2 p a t i e n t s ( 2 0 m e n a n d 1 2

S a c c

h a r o m y c e s

b o u

l a r d

i i

G r o u p A , m e s a l a m i n e ( 1 g )

S . b o u l a r

d i i m a y b e a u s e f u l t o o l i n

I I

2 0 0 0 9 4

c o n t r o l l e d

w o m e n ) a g e d 2 3

4 9 y e a r s

t h r e e - t i m e s d a i l y f o r 6

m a i n t e n a n c e t r e a t m e n t o f C r o h n s d i s e a s e

w i t h C r o h n s d i s e a s e i n c l i n i c a l

m o n t h s ; g r o u p B ,

r e m i s s i o n

m e s a l a m i n e ( 1 g ) t w i c e

d a i l y p l u s a p r e p a r a t i o n o f

S . b o u l a r

d i i ( 1 g ) d a i l y f o r

6 m o n t h s

P r a n t e r a e t a l . ,


4 5 p a t i e n t s ( 8 w

e r e e x c l u d e d )

L a c t o b a c

i l l u s

G G ( L G G )

1 2 x 1 0 9 c f u o f L G G f o r

L G G s e e m s n e i t h e r t o p r e v e n t e n d o s c o p i c

I

2 0 0 2 9 5

p l a c e b o -

o p e r a t e d o n f o r C r o h n s

1 y e a r

r e c u r r e n c e n o r r e d u c e s e v e r i t y o f r e c u r r e n t

c o n t r o l l e d

d i s e a s e

l e s i o n s

M a l c h o w ,


2 8 p a t i e n t s w i t h c o l o n i c C r o h n s E s c h e r

i c h i a c o

l i s t r a i n

D a i l y d o s e o f t w o c a p s u l e s O v e r a l l r a t e o f r e m i s s i o n c o m p a r a b l e i n

I

1 9 9 7 9 6

d o u b l e - b

l i n d ,

d i s e a s e

N i s s l e 1 9 1 7

c o n t a i n i n g

E . c o

l i o f

b o t h g r o u p s

p l a c e b o -

1 0 0 m g ( 2

. 5 x 1 0 1 0 c f u )

c o n t r o l l e d p i l o t

f o r 1 y e a r

B o u s v a r o s


7 5 c h i l d r e n ( 5

2 1 y e a r s o l d )

L a c t o b a c

i l l u s

G G ( L G G )

L G G f o r 2 y e a r s

L G G d i d n o t p r o l o n g t i m e t o r e l a p s e i n

I

e t a l . ,

2 0 0 5 9 7

p l a c e b o -

w i t h C r o h n s d i s e a s e i n

c h i l d r e n w i t h C r o h n s d i s e a s e w h e n g i v e n

c o n t r o l l e d

r e m i s s i o n

a s a n a d j u n c t t o s t a n d a r d t h e r a p y

G u p t a e t a

l . ,

O p e n - l a b e l

4 c h i l d r e n w i t h m i l d - t o - m o d e r a t e

L a c t o b a c

i l l u s

G G ( L G G )

C h i l d r e n r e c e i v e d L G G

L G G m a y i m p r o v e g u t b a r r i e r f u n c t i o n a n d

I I

2 0 0 0 9 8

p i l o t

a c t i v e C r o h n s d i s e a s e

( 1 0 1 0 c f u ) i n e n t e r o c o a t e d

c l i n i c a l s t a t u s i n c h i l d r e n w i t h m i l d l y t o

t a b l e t s t w i c e d a i l y f o r 6

m o d e r a t e l y a c t i v e , s t a b l e C r o h n s d i s e a s e

m o n t h s

S c h u l t z e t a l . ,


1 1 p a t i e n t s w i t h m o d e r a t e - t o -

L a c t o b a c

i l l u s

G G ( L G G )

A l l p a t i e n t s s t a r t e d o n o r a l D i d n o t d e m o n s t r a t e a b e n e f i t o f

I

2 0 0 4 9 9

p l a c e b o -

a c t i v e C r o h n s d i s e a s e

a n t i b i o t i c t r e a t m e n t

L G G i n i n d u c i n g o r m a i n t a i n i n g

c o n t r o l l e d

( c i p r o f l o x a c i n 5 0 0 m g

m e d i c a l l y - i n

d u c e d r e m i s s i o n i n

t w i c e d a i l y

, m e t r o n i d a z o l e C r o h n s d i s e a s e

2 5 0 m g t h r e e - t i m e s d a i l y )

f o r 2 w e e k s

. F o l l o w i n g

w e e k 1 , p a t i e n t s

r a n d o m i z e d t o r e c e i v e

e i t h e r L G G ( n = 5 ) ( 2 x 1 0 9

c f u / d a y ) o r p l a c e b o

( n = 6 )

. P r o b i o t i c

c o n t i n u e d f o r 6 m o n t h s


14/53

14A


T A B L E 5

( c o n t i n u e d ) :

T y p e o f

R e f e r e n c e


P o p u




O u t c o m e

e v i d e n c e

a

K r u i s e t a l . ,

D o u b l e - b l i n d , 1 2 0 p a t i e n t s w i t h i n a c t i v e

E s c h e r

i c h i a c o

l i s t r a i n

T w o t r e a t m e n t s :

P r o b i o t i c t r e a t m e n t a p p e a r s t o o f f e r a n o t h e r

I

1 9 9 7 1 0 0

d o u b l e - d u m m y u l c e r a t i v e c o l i t i s

N i s s l e ( s e r o t y p e 0 6 :

m e s a l a z i n e 5 0 0 m g t h r e e - o p t i o n f o r m a i n t e n a n c e t h e r a p y o f

K 5 : H 1 )

t i m e s d a i l y a n d o r a l

u l c e r a t i v e c o l i t i s

p r e p a r a t i o n o f v i a b l e E . c o

l i

s t r a i n N i s s l e f o r 1 2 w e e k s

I s h i k a w a e t a l . ,


2 1 s u b j e c t s w i t h u l c e r a t i v e c o l i t i s B i f i d o b a c t e r i a f e r m e n t e d B F M ( 1 0 0 m l / d a y ) f o r

S u p p l e m e n t a t i o n w i t h B F M s u c c e s s f u l

I

2 0 0 3 1 0 1

p l a c e b o -

m i l k ( B F M )

1 y e a r

i n m a i n t a i n i n g r e m i s s i o n a n d h a d p o s s i b l e

c o n t r o l l e d

( B i f i d o b a c t e r

i u m

b r e v e

p r e v e n t i v e e f f e c t s o n u l c e r a t i v e c o l i t i s

a n d B . b i f i d u m

)

r e l a p s e s

R e m b a c k e n


1 2 0 p a t i e n t s w i t h a c t i v e

E s c h e r

i c h i a c o

l i s t r a i n

5 9 p a t i e n t s r a n d o m i z e d

T r e a t m e n t w i t h n o n - p a t h o g e n i c E . c o

l i

I

e t a l . ,

1 9 9 9 1 0 2

s i n g l e - c e n t r e ,

u l c e r a t i v e c o l i t i s , 1 1 6

N i s s l e 1 9 1 7

t o m e s a l a z i n e , 5 7 t o

h a d e q u i v a l e n t e f f e c t t o m e s a l a z i n e i n

d o u b l e - d u m m y p a r t i c i p a t e d

E . c o

l i . A l l p a t i e n t s

m a i n t a i n i n g r e m i s s i o n o f u l c e r a t i v e c o l i t i s

a l s o r e c e i v e d s t a n d a r d

m e d i c a l t h e r a p y t o g e t h e r

w i t h 1 - w e e k o f o r a l

g e n t a m i c i n

K r u i s e t a l . ,

D o u b l e - b l i n d , 3 2 7 p a t i e n t s ( 1 8

7 0 y e a r s o l d ) E s c h e r

i c h i a c o

l i s t r a i n

1 6 2 p a t i e n t s r e c e i v e d

P r o b i o t i c s h o w e d e f f i c a c y a n d s a f e t y i n

I

2 0 0 4 1 0 3

d o u b l e - d u m m y w i t h u l c e r a t i v e c o l i t i s i n r e m i s s i o n N i s s l e 1 9 1 7

p r o b i o t i c 2 0 0 m g o n c e

m a i n t a i n i n g r e m i s s i o n e q u i v a l e n t t o g o l d

d a i l y a n d 1 6 5 p a t i e n t s

s t a n d a r d m e s a l a z i n e i n u l c e r a t i v e c o l i t i s

r e c e i v e d m e s a l a z i n e

5 0 0 m g t h r e e - t i m e s d a i l y

f o r 1 2 m o n t h s

B i b i l o n i e t a l . ,

O p e n - l a b e l

4 4 ( 4 2 c o m p l e t e d t h e s t u d y )

V S L # 3 b

V S L # 3 b t r e a t m e n t f o r 6

I n t h e s e p a t i e n t s , n o t r e s p o n d i n g t o

I I

2 0 0 5 1 0 4

a m b u l a t o r y a d u l t p a t i e n t s w i t h

w e e k s ( 3 6 0 0 x 1 0 9 b a c t e r i a c o n v e n t i o n a l t h e r a p y , V

S L # 3 b r e s u l t e d i n a

a c t i v e u l c e r a t i v e c o l i t i s

d a i l y i n t w o d i v i d e d

c o m b i n e d r e m i s s i o n / r e s p o n s e r a t e o f 7 7 %

d o s e s )

w i t h n o a d v e r s e e v e n t s

F u r r i e e t a l . ,


1 8 a d u l t s w i t h a c t i v e u l c e r a t i v e


l o n g u m

2 x 1 0 1 1 f r e e z e - d r i e d

S h o r t - t e r m s y n b i o t i c t r e a t m e n t o f a c t i v e

I

2 0 0 5 1 0 5

d o u b l e - b

l i n d ,

c o l i t i s

v i a b l e B i f i d o b a c t e r i u m

u l c e r a t i v e c o l i t i s r e s u l t e d i n i m p r o v e m e n t

c o n t r o l l e d p i l o t

l o n g u m

i n a g e l a t i n

o f f u l l c l i n i c a l a p p e a r a n c e o f c h r o n i c

c a p s u l e a n d a s a c h e t

i n f l a m m a t i o n

o f 6 g p r e b i o t i c t w i c e d a i l y

f o r 4 w e e k s


15/53

15A


K a t o e t a l . ,


2 0 p a t i e n t s w i t h m i l d - t o -

B i f i d o b a c t e r i a f e r m e n t e d 1 0 0 m l / d a y b i f i d o b a c t e r i a S u p p l e m e n t a t i o n w i t h t h i s B F M p r o d u c t

I

2 0 0 4 1 0 6

p l a c e b o -

m o d e r a t e , a c t i v e , u l c e r a t i v e

m i l k ( B F M ) c o n t a i n i n g

f e r m e n t e d m i l k ( 1 0 x 1 0 9

w a s s a f e a n d m o r e e f f e c t i v e t h a n c o n v e n t i o n a l

c o n t r o l l e d

c o l i t i s


b r e v e ,

b a c t e r i a / 1 0 0 m l b o t t l e ) f o r t r e a t m e n t a l o n e , s u g g e s t i n g p o s s i b l e


b i f i d u m

1 2 w e e k s

b e n e f i c i a l e f f e c t s i n m a n a g i n g a c t i v e

a n d L a c t o b a c

i l l u s

u l c e r a t i v e c o l i t i s

a c i d o p

h i l l u s

G u s l a n d i e t a l . ,

P i l o t

2 5 p a t i e n t s ( 1 9

4 7 y e a r s o l d )

S a c c

h a r o m y c e s

b o u

l a r d

i i

H i g h - d o s e m e s a l a z i n e

P r e l i m i n a r y r e s u l t s s u g g e s t e d S . b o u l a r

d i i

I I

2 0 0 3 1 0 7

w i t h a m i l d - t o - m o d e r a t e c l i n i c a l

( 1 g t h r e e t i m e s d a i l y )

c a n b e e f f e c t i v e i n t r e a t m e n t o f u l c e r a t i v e

f l a r e - u p o f u l c e r a t i v e c o l i t i s

f o r a t l e a s t 3 m o n t h s ;

c o l i t i s

S . b o u l a r

d i i a d m i n i s t e r e d f o r

4 w e e k s a s 2 5 0 m g c a p s u l e

t h r e e - t i m e s d a i l y w h i l e

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3 0 p a t i e n t s w i t h a c t i v e u l c e r a t i v e B I F I C O p r o b i o t i c c a p s u l e P a t i e n t s r e c e i v e d

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I

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n d

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p r e v e n t i n g f l a r e - u p s o f c h r o n i c u l c e r a t i v e

l a c t o b a c i l l i t r i p l e v i a b l e

r a n d o m l y a d m i n i s t e r e d

c o l i t i s

. M a y b e c o m e a p r o p h y l a c t i c d r u g

b a c t e r i a

B I F I C O t r i p l e v i a b l e c a p s u l e t o d e c r e a s e r e l a p s e o f u l c e r a t i v e c o l i t i s

( 1 . 2

6 g / d a y ) , o

r a n

i d e n t i c a l p l a c e b o

( s t a r c h ) f o r 8 w e e k s

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V S L # 3 b

P a t i e n t s r a n d o m i z e d t o

N o

s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e b e t w e e n

I I

2 0 0 0 1 0 9

t w o p a r a l l e l

d i s e a s e i n r e m i s s i o n

e i t h e r r i f a x i m i n ( 1

. 8 g / d a y ) p r o b i o t i c a n d m e s a l a m i n e

g r o u p s

f o r 3 m o n t h s f o l l o w e d b y

p r o b i o t i c c o c k t a i l V S L # 3 b

f o r 9 m o n t h s o r

m e s a l a z i n e ( 4 g / d a y )


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l . ,

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i l l u s

G G ( L G G )

P a t i e n t s r a n d o m i z e d t o L G G I n t h i s s m a l l s t u d y

, a f t e r 1 2 m o n t h s

I I

2 0 0 3 1 1 0

t h r e e p a r a l l e l

w i t h q u i e s c e n t C r o h n s d i s e a s e

( 1 8 x 1 0 9 v i a b l e b a c t e r i a /

t r e a t m e n t t h e r e w a s n o s t a t i s t i c a l l y s i g n i f i c a n t

g r o u p s , s

i n g l e -

d a y ) o r m e s a l a z i n e

d i f f e r e n c e b e t w e e n p r o b i o t i c a n d m e s a l a z i n e

b l i n d e d

( 2 . 4

g / d a y ) o r L G G ( 1 8 x

1 0 9 v i a b l e b a c t e r i a / d a y )

p l u s m e s a l a z i n e ( 2

. 4 g / d a y )


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O p e n s t u d y

1 0 p a t i e n t s w i t h u l c e r a t i v e c o l i t i s L a c t o b a c i l l i ( L A - 5 ) ,

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S u g g e s t e d t h a t p r o b i o t i c s p r i m a r i l y a c t

I I

2 0 0 3 1 1 1

w h o u n d e r w e n t i l e a l p o u c h

b i f i d o b a c t e r i a ( B b - 1 2 )

( 5 0 0 m l ) c o n t a i n i n g l i v e

s u p e r f i c i a l l y

, c h a r a c t e r i z e d b y c h a n g e

a n a l a n a s t o m o s i s

l a c t o b a c i l l i ( L A - 5

) a n d

i n g r o s s a p p e a r a n c e o f m u c o s a a t

b i f i d o b a c t e r i a ( B b - 1 2 )

e n d o s c o p y , b u t w i t h o u t s i g n i f i c a n t e f f e c t

g i v e n d a i l y f o r 4 w e e k s

o n

h i s t o l o g i c a l p i c t u r e , m u c o s a l

p e r f u s i o n o r f a e c a l c a l p r o t e c t i n


16/53


17/53

17A


Ulcerative colitis

A study of the intestinal microflora of IL-10knockout mice revealed that, as colitisdeveloped between 2 and 8 weeks of age,there was a decrease in the numbers of lactobacilli. 124 Indeed, by repopulating themice with supplemental lactobacilli thehistological severity of the colitis wasattenuated and the amount of mucosaladherence and invasion by aerobic bacteriawas decreased. Several studies haveevaluated the effects of probiotic treatmentin human ulcerative colitis. 100 108 Clinicalstudies of affected patients have demonstratedthe efficacy of probiotics, most notably E. coli(strain Nissle 1917), in maintaining remissionin ulcerative colitis at a rate equivalent totreatment with mesalamine. 100,102,103

Pouchitis

Pouchitis, a common complication of ilealpouch anal anastomosis (IPAA) surgery for ulcerative colitis, is a non-specificinflammatory disease of the ileal reservoir.The clinical frequency of pouchitis variesdepending on the duration of the follow-up,but it is approximately 50% after 10 years 125

Although the causes of pouchitis remainlargely unknown, some studies havereported reduced counts of lactobacilli andbifidobacteria within the pouch, 126 which

suggests that these bacteria may play a rolein the development of this syndrome.Moreover, the majority of pouchitis casesrespond to treatment with antimicrobialagents. The therapeutic potential of probiotics for pouchitis has been studied inseveral clinical trials. 111 122,125

There is strong evidence to support the useof 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

W o o d c o c k


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I

e t a l . ,

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c o n t r o l l e d

L . p l a n t a r u m

d u r i n g

d o e s n o t o c c u r i n h u m a n s . S i g n i f i c a n c e o f

i m m e d i a t e p r e - o p e r a t i v e

t h e i n c r e a s e i n I g M a t t h e m u c o s a l s u r f a c e i n

p e r i o d

t h e c o n t r o l s w a s u n c l e a r

M c N a u g h t


1 2 9 p a t i e n t s u n d e r g o i n g e l e c t i v e

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e t a l . ,

2 0 0 2 1 2 1


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2 9 9 v

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c o n t r o l l e d


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d a y w i t h 5 x 1 0 7 c f u / m l )

c o l o n i z a t i o n , o r i n c i d e n c e o f

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