Probiotik Clinical Applications in Gastrointestinal Disease

More than 500 microbial species
About 1 1,5 kg of our body weight

100,000,000,000,000 individual cells
The GI tract is sterile in normal fetus
Bacterial colonization
Bifidobacteria
Defense mechanism
Bifidobacterium
Lactobacillus
Friendly bacteria
Escherichia
Glostridium
Staphylococcus
Pathogenic bacteria
Bacteriodes
Opportunistic bacteria
Veillonella
Gut peristaltic
Gastric acid
Gut secretion ( bile, pancreatic juices, immonuglobulins )
Intestinal mucous
Mucosal blood flow
Enterocyte regeneration
~25 40 % of the gut is

lymphoid tissue
Up to 70% of all the immune
cells are located in the
instestine
Dietary components
Digestion products
Intimate contact with immune system of gut
( Gut Associated Lymphoid Tissue )
food + microorgansims = necessary for development of
GALT
Ruthlein. 1992
Treatment of acute diarrhea

Prevention of acute diarrhea
Prevention of nosocomial diarrhea
Treatment of Antibiotic Associated Diarrhea (AAD)
Prevention of AAD
Randomized Clinical Trials

Children with acute diarrhea
Yogurt vs placebo
Decrease duration of diarrhea
Isolauri et al ( 1994), Reza et al ( 1995 ), Pant et al ( 1995 )
RCT of Probiotic for treatment of

acute diarrhea
PROBIOTIC
AUTHORS
DAY
TREATMENT
GROUP
CONTROL
GROUP
L rhamnosus
Isolauri, 1991
Raza, 1995
Pant, 1996
Shomikova, 1997
Guandalini, 2000
71
40
26
123
287
5
2
2
5
5
1.4 days
31% ( at day 2 )
1.9 days
2.7 days
2.4 days
2.4 days
75% ( at day 2 )
3.3 days
3.7 days
3.0 days
L reuteri
Shomikova, 1997
Shomikova, 1997
66
40
5
5
1.5 days
26% ( at day 2 )
2.5 days
81% ( at day 2 )
S boulardii
Cetina Sauri, 1989
130
15% ( at day 2 )
60% ( at day 2 )
55 infants aged 5 24 months hospitalized for

non- GI disease.
Formula : Bifidobacteria vs control
Observe for 7 months
Diarrhea episode decreased ( 7 % vs 31 % )
Rotavirus enfection decreased ( 10 % vs 39 % )
Saavedra et al, 1994
ND is major problem in pediatric hospital worldwide

81 children aged 1 36 months hospitalized for reason
other than diarrhea.
RCT : LGG ( n = 45 ) vs placebo ( n = 36 )
LGG 6 x 109 cfu twice daily
LGG reduced the risk of nosocomial diarrhea in
comparison with placebo ( 6,7% vs 33,3 % )
LGG significantly reduced the risk of rotavirus
gastroenteritis ( 2,2% vs 17,7 % )
Antibiotic associated diarrhea

Metronidazole / vancomicyn
Relapse
Treatment with Lactobaillus casei
Bacteria-produced substance inhibit in vitro the
growth of enteropatogens, including C.difficille
Prevent relapse of C difficille diarrhea
RCT of probiotic for prevention of

antibiotic-associated diarrhea
PROBIOTIC
AUTHORS
DAY
TREATMENT
GROUP
% DIARRHEA
CONTROL
GROUP
% DIARRHEA
S boulardii
Adam, 1977
Surawicz, 1989
McFarland, 1995
388
180
193
7
28
28
4.5
9.9
7.2
17.5
21.8
14.6
L rhamnosus
Vanderhoof, 1999
Arvoie, 1999
188
167
10
30
8
5
26
16
B longum
Orrhage, 1994
20
21
20
70
E faecium
Wunderlich, 1989
45
8.7
27.2
Helicobacter pylori
Lactose intolerance
Ulcerative colitis
Necrotizing Enterocolitis
In vitro and in vivo data support the use of

probiotics in Hp infections
Adding probiotic to the standard tretment of Hp
infections ( PPI and 2 antibiotics ) reduced side
effects and improve compliances.
Need more trials to replace current treatment
on Hp infections
Children with lactose malabsorption ( BHT )

Milk, yogurt, pasteurized yogurt
Administration of yogurt decrease H2 production
and decrease symptom of lactose intolerance
Sherber et al, 1995 ; Montes et al, 1995
Pre and post test design, Jakarta

42/66 Junior High School students ( 12 -14 years old ) are
lactose intolerance using BHT
Full-cream milk for 1 week : all symptoms appeared :
borborigmy, flatus, adbominal distention, nausea, vomiting,
abdominal pain, and diarrhea.
After 2 weeks of treatment with probiotic, 40 children free
of symptoms
Only 2 children still having abdominal distension and flatus
Boediarso et al, 2005
RCT in 18 patients of active UC

Bifidobacterium longum + FOS (1 month)
Clinical status, laboratory and biopsy
Sigmoidescopy score reduced ( p < 0,05 )
mRNA levels for human beta defensins 2,3 and 4
reduced ( p < 0,05 )
TNF, interleucin 1 reduced ( p < 0,05 )
Reduced inflammation in biopsy specimen
Furrie et al, 2005
Reduced NEC in an infant study in 585 VLBW

infants in 12 NICUs in Italy using Lactobacillus GG
with historical controls
( Hoyots et al, 1999 )
Infants given probiotic were less likely than control
infants to develop NEC; 1,4 % vs 2,8 %, not
statiscally significant
( Dani et al, 2002 )
A double blind, placebo controlled, randomized trial.

14 child care center, Israel.
Healthy infants aged 4 10 months, 12 weeks feeding and
observation.
201 infants : control 60, B lactis 73, L reuteri 68
Infants fed probiotic supplemented formula had fewer and
shorter episodes of diarrhea.
No effect on respiratory illnesses
The effect more prominent with L reuteri
Weizman et al, 2005
RCT over 7 month

To examine whether long term consumption or a probiotic milk could
reduce respiratory infections in children in daycare centers.
18 daycare centers in Helsinki, Finland.
571 healthy children aged 1- 6 years, 282 in intervention group and
289 in the control group.
Milk with our without Lactobacillus GG, 260 ml daily
Lactobacillus reduce respiratory infections and their severity among
children in daycare center.
Hatakka et al, 2001
Competitive inhibition of bacterial adhesion

Synthesis of compounds that inhibit or destroy
pathogens
Stimulation of immune response to pathogens
Competitive consumption of nutrient required for
growth of pathogens.
A recent review of 143 human clinical trials of

probiotics between 1961 and 1998 involving more
than 7500 subjects found no adverse events.
1.
2.
3.
4.
5.
6.
7.
8.
Epidemiologic links between less exposure to microbes and allergic disease,

and protective effects of higher microbial burden.
Intestinal microbiotica are the largest source of microbial exposure through early
immune development
Intestinal microbiotica appear to be essential for development of oral tolerance
Changing patterns of microbiotica with progressive Westernization and links with
allergic disease.
Differences in perinatal colonization in children who go on to develop allergic
disease
Perinatal administration of probiotics associated with anti-inflammatory and
immunoregulatory effects on immune function.
Presymptomatic immune dysregulation evident in infants and newborns who
later develop allergic disease, suggesting that ellergy prevention should be
initiated early.
Initial studies with probiotics suggested promise in the prevention and early
treatment of allergis disease.
Mengaktivasi makrofag untuk meningkatkan

pemaparan antigen dengan limfosit B.
Meningkatkan produksi secretory IgA baik secara
lokal maupun sistemik
Memodulasi sitokin
Sumber : WGO, 2008.19
Mencerna makanan dan kompetitif nutrisi terhadap

patogen.
Mempengaruhi PH lokal untuk membuat kondisi yang
tidak menguntungkan untuk patogen.
Memproduksi bakteriosin untuk menghambat patogen.
Stimulasi produksi epithelial mucin.
Memperkuat fungsi barrier intestinal.
Kompetitif adhesi terhadap patogen.
Sumber : WGO.2008.19
Probiotics appear to be useful in the prevention or

treatment of several gastrointestinal disorders,
including infectious diarrhea, antibiotic associated
diarrhea, nosocomial diarrhea , and lactose
intolerance.
Safety does not appera to be a sginificant concern.
Research on probiotics in some diseases should
be done to get more clinical evidences

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More than 500 microbial species

About 1 1,5 kg of our body weight

~25 40 % of the gut is

Treatment of acute diarrhea

Randomized Clinical Trials

Isolauri et al ( 1994), Reza et al ( 1995 ), Pant et al ( 1995 )

RCT of Probiotic for treatment of

Cetina Sauri, 1989

55 infants aged 5 24 months hospitalized for

ND is major problem in pediatric hospital worldwide

Antibiotic associated diarrhea

RCT of probiotic for prevention of

In vitro and in vivo data support the use of

Children with lactose malabsorption ( BHT )

Sherber et al, 1995 ; Montes et al, 1995

Pre and post test design, Jakarta

RCT in 18 patients of active UC

Reduced NEC in an infant study in 585 VLBW

A double blind, placebo controlled, randomized trial.

RCT over 7 month

Competitive inhibition of bacterial adhesion

A recent review of 143 human clinical trials of

Epidemiologic links between less exposure to microbes and allergic disease,

Mengaktivasi makrofag untuk meningkatkan

Mencerna makanan dan kompetitif nutrisi terhadap

Probiotics appear to be useful in the prevention or

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