Probiotics

1. PROBIOTCSPROBIOTCS
ByBy
Dr. Tarek ShetaDr. Tarek Sheta
Lecturer of internal medicineLecturer of internal medicine
Mansoura Faculty of MedicineMansoura Faculty of Medicine

2.  First described byFirst described by
Metchnikoff (a RussianMetchnikoff (a Russian
scientist and professorscientist and professor
at the Pasteur Instituteat the Pasteur Institute
in Paris) inin Paris) in 19081908..
“Live microbial food“Live microbial food
ingredients that alteringredients that alter
the microflora andthe microflora and
confer health benefit”confer health benefit”
ProbioticsProbiotics
 First described byFirst described by
Metchnikoff (a RussianMetchnikoff (a Russian
scientist and professorscientist and professor
at the Pasteur Instituteat the Pasteur Institute
in Paris) inin Paris) in 19081908..
“Live microbial food“Live microbial food
ingredients that alteringredients that alter
the microflora andthe microflora and
confer health benefit”confer health benefit”

3. PROBIOTICS (BACTERIOTHERAPY)PROBIOTICS (BACTERIOTHERAPY)
FAO/WHO DefinitionFAO/WHO Definition
 NonNon--pathogenic livingpathogenic living
organisms that exert aorganisms that exert a
positive influence on thepositive influence on the
health of the host animal.health of the host animal.
 Administered in both drugAdministered in both drug
form and as components ofform and as components of
foods and beverages.foods and beverages.
 NonNon--pathogenic livingpathogenic living
organisms that exert aorganisms that exert a
positive influence on thepositive influence on the
health of the host animal.health of the host animal.
 Administered in both drugAdministered in both drug
form and as components ofform and as components of
foods and beverages.foods and beverages.

4. Prebiotics: definitionPrebiotics: definition
 NonNon--digestible fooddigestible food
supplements or ingredients.supplements or ingredients.
 Not absorbed or degradedNot absorbed or degraded
in the intestine.in the intestine.
 NonNon--digestible fooddigestible food
supplements or ingredients.supplements or ingredients.
 Not absorbed or degradedNot absorbed or degraded
in the intestine.in the intestine.

5. PrebioticsPrebiotics
 They stimulate the growth and activity of certainThey stimulate the growth and activity of certain
species of bacteria in the colon.species of bacteria in the colon.
 OligosaccheridesOligosaccherides
 InulinInulin
 garlicgarlic
 onionsonions
 Asparagus,Asparagus,
 whole wheatwhole wheat
 Fiber supplementsFiber supplements
 They stimulate the growth and activity of certainThey stimulate the growth and activity of certain
species of bacteria in the colon.species of bacteria in the colon.
 OligosaccheridesOligosaccherides
 InulinInulin
 garlicgarlic
 onionsonions
 Asparagus,Asparagus,
 whole wheatwhole wheat
 Fiber supplementsFiber supplements

6. Prebiotics: Health benefitsPrebiotics: Health benefits
 Promotion of growth of probiotics.Promotion of growth of probiotics.
 Production of short chain fatty acids.Production of short chain fatty acids.
 Increase of calcium absorption.Increase of calcium absorption.
 Decrease glucose absorption.Decrease glucose absorption.
 Promotion of growth of probiotics.Promotion of growth of probiotics.
 Production of short chain fatty acids.Production of short chain fatty acids.
 Increase of calcium absorption.Increase of calcium absorption.
 Decrease glucose absorption.Decrease glucose absorption.

7. Prebiotic vs ProbioticPrebiotic vs Probiotic
PrebioticPrebiotic
 Usually carbohydrateUsually carbohydrate
 Not aliveNot alive
 Beneficial health effectBeneficial health effect
 Food ingredientFood ingredient
 Act on microbiotaAct on microbiota
 Focus is colonFocus is colon, but broader, but broader
effects also seeneffects also seen
ProbioticProbiotic
 MicroorganismMicroorganism
 AliveAlive
 Beneficial health effectBeneficial health effect
 Food, dietary supplement,Food, dietary supplement,
drugsdrugs
 May act on microbiota, butMay act on microbiota, but
other mechanismsother mechanisms
 Can act on numerous sitesCan act on numerous sites
around the bodyaround the body
 Usually carbohydrateUsually carbohydrate
 Not aliveNot alive
 Beneficial health effectBeneficial health effect
 Food ingredientFood ingredient
 Act on microbiotaAct on microbiota
 Focus is colonFocus is colon, but broader, but broader
effects also seeneffects also seen
 MicroorganismMicroorganism
 AliveAlive
 Beneficial health effectBeneficial health effect
 Food, dietary supplement,Food, dietary supplement,
drugsdrugs
 May act on microbiota, butMay act on microbiota, but
other mechanismsother mechanisms
 Can act on numerous sitesCan act on numerous sites
around the bodyaround the body

8. Synbiotic = Probiotic + PrebioticSynbiotic = Probiotic + Prebiotic

9. SynbioticsSynbiotics
 A combination between a probioticA combination between a probiotic
organism in combination with itsorganism in combination with its
prebiotic food.prebiotic food.
 Improves survivaImproves survivall and colonization byand colonization by
probioticsprobiotics..
 More effective than probiotics aloneMore effective than probiotics alone..
 A combination between a probioticA combination between a probiotic
organism in combination with itsorganism in combination with its
prebiotic food.prebiotic food.
 Improves survivaImproves survivall and colonization byand colonization by
probioticsprobiotics..
 More effective than probiotics aloneMore effective than probiotics alone..

10. Characteristics of EffectiveCharacteristics of Effective
ProbioticsProbiotics
 Survive the stomach acid and bile.Survive the stomach acid and bile.
 Adhere to intestinal mucosal lining.Adhere to intestinal mucosal lining.
 non pathogenic and non toxic.non pathogenic and non toxic.
 Grow and establish temporaryGrow and establish temporary
residence in the intestineresidence in the intestine
 Import health benefitsImport health benefits
Characteristics of EffectiveCharacteristics of Effective
ProbioticsProbiotics
 Survive the stomach acid and bile.Survive the stomach acid and bile.
 Adhere to intestinal mucosal lining.Adhere to intestinal mucosal lining.
 non pathogenic and non toxic.non pathogenic and non toxic.
 Grow and establish temporaryGrow and establish temporary
residence in the intestineresidence in the intestine
 Import health benefitsImport health benefits

11. Different types of bacteria used asDifferent types of bacteria used as
probioticsprobiotics
Lactobacillus speciesLactobacillus species
 L. acidophilusL. acidophilus
 L. plantarumL. plantarum
 L. casei subspecies rhamnosusL. casei subspecies rhamnosus
 L. brevisL. brevis
 L. delbreuckii subspecies bulgaricusL. delbreuckii subspecies bulgaricus
Bifidobacterium speciesBifidobacterium species
 B. adolescentisB. adolescentis
 B. bifidumB. bifidum
 B. longumB. longum
 B. infantisB. infantis
 B. breveB. breve
Lactobacillus speciesLactobacillus species
 L. acidophilusL. acidophilus
 L. plantarumL. plantarum
 L. casei subspecies rhamnosusL. casei subspecies rhamnosus
 L. brevisL. brevis
 L. delbreuckii subspecies bulgaricusL. delbreuckii subspecies bulgaricus
Bifidobacterium speciesBifidobacterium species
 B. adolescentisB. adolescentis
 B. bifidumB. bifidum
 B. longumB. longum
 B. infantisB. infantis
 B. breveB. breve

12. Other speciesOther species
 Escherichia coliEscherichia coli
 StreptococcusStreptococcus
 SaccharomycesSaccharomyces
 Several combinationsSeveral combinations
on the marketon the market
 Escherichia coliEscherichia coli
 StreptococcusStreptococcus
 SaccharomycesSaccharomyces
 Several combinationsSeveral combinations
on the marketon the market

13. Clinical Effects are strainClinical Effects are strain--
specificspecific
•• Different strains of the same species can beDifferent strains of the same species can be
different.different.

14. Potential Mechanisms of Action of ProbioticsPotential Mechanisms of Action of Probiotics

15. Levels of Probiotic ActivityLevels of Probiotic Activity
Interfere with
growth or survival
of bacteria in gut
lumen
Improve mucosal
barrier function and
mucosal immune
system
Adapted from Rijkers GT, et al. J Nutr. 2010;140:671S-676S.
Improve mucosal
barrier function and
mucosal immune
system
Affect systemic
immune system

16. CLINICAL APPLICATIONS
OF PROBIOTICS
H. pylori
Eradication
Diarrhea
Acute infectious
Antibiotic-associated
C. difficile
IBD
Ulcerative colitis
Crohn’s disease
Pouchitis
Constipation
Lactose
Intolerance

17. DiarrheaDiarrhea
 Treatment of acute diarrhea:
It has been confirmed that different
probiotic strains are useful in reducing
the severity and duration of acute
infectious diarrhea in children.
 The evidence from studies on viral
gastroenteritis is more convincing than
the evidence on bacterial or parasitic
infections.
PROBIOTICS IN GI DISEASES
DiarrheaDiarrhea
 Treatment of acute diarrhea:
It has been confirmed that different
probiotic strains are useful in reducing
the severity and duration of acute
infectious diarrhea in children.
 The evidence from studies on viral
gastroenteritis is more convincing than
the evidence on bacterial or parasitic
infections.

18. Control (Control (1919)) L. reuteri/L. reuteri/
L. rhamnosusL. rhamnosus
((2424))
PP--valuevalue
Duration of diarrheaDuration of diarrhea
(hours)(hours) 115115..77 7575..99 00..0505
Treatment of Acute DiarrheaTreatment of Acute Diarrhea
5 Day Therapy in Danish Children (9 to 44 months) in Day Care with Acute Diarrhea
Duration of diarrheaDuration of diarrhea
(hours)(hours) 115115..77 7575..99 00..0505
Duration of wateryDuration of watery
diarrheadiarrhea 3737 3838..11 00..9494
Duration of fever (days)Duration of fever (days)
11..11 11..44 00..5959
Diarrhea afterDiarrhea after 120120 hourshours
77 22 00..0303
V Rosenfeldt, et al. Pediatr Infect Dis J 21:417-9, 2002

19. Prevention of acute diarrhea:Prevention of acute diarrhea:
 RadiationRadiation--induced diarrheainduced diarrhea
 Traveller’s diarrhea.
 In the prevention of adult andadult and
childhood diarrheachildhood diarrhea, there is
only suggestive evidence that
Lactobacillus GG, L. casei DN-114
001, and S. boulardii are effective in
some specific settings
 RadiationRadiation--induced diarrheainduced diarrhea
 Traveller’s diarrhea.
 In the prevention of adult andadult and
childhood diarrheachildhood diarrhea, there is
only suggestive evidence that
Lactobacillus GG, L. casei DN-114
001, and S. boulardii are effective in
some specific settings

20. Yogurt (Yogurt (364364)) Yogurt+Yogurt+
L. caseiL. casei
((360360))
PP--valuevalue
Children withChildren with
diarrheadiarrhea 8787 ((2222%)%) 6161 ((1616%)%) 00..029029
Prevention of Diarrheal IllnessPrevention of Diarrheal Illness
18 Week Therapy in French Children (6-24 months) in Day Care
Children withChildren with
diarrheadiarrhea 8787 ((2222%)%) 6161 ((1616%)%) 00..029029
Duration ofDuration of
diarrhea (days)diarrhea (days) 33..9595 33..5353 00..2424
Rotavirus positiveRotavirus positive
stoolstool 22..22%% 00..33%%
CA Pedone, et al. Int J Clin Pract 54(9):568-71, 2000

21. AntibioticAntibiotic--associated diarrhea:associated diarrhea:
 One study indicated
that L. casei DN-114
001 is effective in
hospitalized adult
patients for preventing
antibiotic-associated
diarrhea and C. difficile
diarrhea.
 One study indicated
that L. casei DN-114
001 is effective in
hospitalized adult
patients for preventing
antibiotic-associated
diarrhea and C. difficile
diarrhea.

22. Probiotics for the Prevention ofProbiotics for the Prevention of
Antibiotic Associated DiarrheaAntibiotic Associated Diarrhea
Mixtures included:
Lactinex = L. acidophilus and L. bulgaricus;
Lactobacillus acidophilus and Bifidobacterium lactis;
Lactobacillus acidophilus and Bifidobacterium infantis.
McFarland, Am J Gastroenterol 2006; 101(4): 812-822.

23. S. boulardii Is Effective in Patients with
Recurrent C. difficile Disease
Initial CDD
CDDrecurrence,%
P=NS
Recurrent CDD
P=0.04
CDDrecurrence,%
CDD=Clostridium difficile-associated disease
McFarland L, et al. JAMA. 1994;271:1913-1918.
CDDrecurrence,%
S. boulardii
(n=31)
Placebo
(n=33)
Control
(n=34)
Patients received standard antibiotics (vancomycin or metronidazole) and S. boulardii 1 g/day or placebo
for 4 weeks.
CDDrecurrence,%
S. boulardii
(n=26)

24. Probiotics in C. Difficile-Associated Disease
RCTs of Probiotics for Treatment
of C. difficile Disease
BB=Bifidobacterium bifidum; LA=Lactobacillus acidophilus; LGG=Lactobacillus
rhamnosus GG; LP=Lactobacillus plantarum 299v; SB=Saccharomyces boulardii
MacFarland LV. Am J Gastroenterol. 2006;101:812-822.

25. Eradication ofEradication of
Helicobacter pyloriHelicobacter pylori
 Certain probiotics may be helpful as
adjuvant therapy with antibiotics in the
eradication of H. pylori infection.
 Several lactobacilli and bifidobacterial
strains reduce the side effects of
antibiotic therapies and improve patient
compliance.
 Certain probiotics may be helpful as
adjuvant therapy with antibiotics in the
eradication of H. pylori infection.
 Several lactobacilli and bifidobacterial
strains reduce the side effects of
antibiotic therapies and improve patient
compliance.

26.  A meta-analysis of 14 randomized trials
suggests that supplementation of anti–H.
pylori antibiotic regimens with certain
probiotics may be effective in increasing
eradication rates.
 There is no evidence to support that a
probiotic alone, without concomitant
antibiotic therapy, would be effective.
 A meta-analysis of 14 randomized trials
suggests that supplementation of anti–H.
pylori antibiotic regimens with certain
probiotics may be effective in increasing
eradication rates.
 There is no evidence to support that a
probiotic alone, without concomitant
antibiotic therapy, would be effective.

27. Probiotics in irritable bowel syndrome
(IBS)
 IBS includes a range of symptoms, such as
abdominal pain, altered bowel habits, bloating
and flatulence in the absence of structural
abnormalities in the intestine.
 IBS includes a range of symptoms, such as
abdominal pain, altered bowel habits, bloating
and flatulence in the absence of structural
abnormalities in the intestine.

28.  Studies have observed alterations in intestinal
microflora in patients and increased symptoms
following enteric infections, therefore
probiotics might be a useful tool to improve
symptoms.
 A reduction in abdominal bloating and
flatulence as a result of probiotic treatments is
a consistent finding in published studies; some
strains may ameliorate pain and provide global
relief (B. infantis 35624). Lactobacillus reuteri
may improve colicky symptoms within one
week of treatment.
 Studies have observed alterations in intestinal
microflora in patients and increased symptoms
following enteric infections, therefore
probiotics might be a useful tool to improve
symptoms.
 A reduction in abdominal bloating and
flatulence as a result of probiotic treatments is
a consistent finding in published studies; some
strains may ameliorate pain and provide global
relief (B. infantis 35624). Lactobacillus reuteri
may improve colicky symptoms within one
week of treatment.

29. Summary of Key Randomized ControlledSummary of Key Randomized Controlled
Trials of Probiotics in IBSTrials of Probiotics in IBS
William D Chey, Reviews in Gastroenterol 2010

30. Probiotics after gut surgery
 Roux-en Y gastric bypass surgery (one type
of bariatric surgery) is an effective treatment
of morbid obesity.
 Problems that occur post operatively are
alteration of microflora with bacterial
overgrowth (BO) in the blind sac of the
intestine, intestinal pain, and possibly
impaired vitamin B12 status (due to lack of
intrinsic factor production from the
stomach).
 Roux-en Y gastric bypass surgery (one type
of bariatric surgery) is an effective treatment
of morbid obesity.
 Problems that occur post operatively are
alteration of microflora with bacterial
overgrowth (BO) in the blind sac of the
intestine, intestinal pain, and possibly
impaired vitamin B12 status (due to lack of
intrinsic factor production from the
stomach).

31.  Probiotic treatment (6 mo)
in 44 post operational
patients. BO improved
only after 6 mo, but not
earlier.
 Vitamin B12 status
improved, gastrointestinal
symptoms remained
unchanged, but post
operational weight loss
was significantly increased
in the probiotic group.
 Probiotic treatment (6 mo)
in 44 post operational
patients. BO improved
only after 6 mo, but not
earlier.
 Vitamin B12 status
improved, gastrointestinal
symptoms remained
unchanged, but post
operational weight loss
was significantly increased
in the probiotic group.

32. Lactose intolerance
 Streptococcus
thermophilus and
Lactobacillus
delbrueckii subsp.
Bulgaricus
improve lactose
digestion and
reduce symptoms
related to lactose
intolerance.
 Streptococcus
thermophilus and
Lactobacillus
delbrueckii subsp.
Bulgaricus
improve lactose
digestion and
reduce symptoms
related to lactose
intolerance.

33. Necrotizing enterocolitis
 Probiotics supplementation reduces the risk
of necrotizing enterocolitis in preterm
neonates.
 Systematic reviews of randomized controlled
trials have also shown a reduced risk of
death in probiotic treated groups.
 Probiotics supplementation reduces the risk
of necrotizing enterocolitis in preterm
neonates.
 Systematic reviews of randomized controlled
trials have also shown a reduced risk of
death in probiotic treated groups.

34. Probiotics in Ulcerative Colitis
 Various probiotic species have shown promise inVarious probiotic species have shown promise in
management of ulcerative colitis.management of ulcerative colitis.
 Prevention of relapse is more clinicalyPrevention of relapse is more clinicaly
documented than the treatment of active disease.documented than the treatment of active disease.

35.  The following are illustrative controlled trials:The following are illustrative controlled trials:
 E. coli was as effective as lowE. coli was as effective as low--dosedose 55--
aminosalicylic acid (aminosalicylic acid (55--ASA) in preventingASA) in preventing
relapse of ulcerative colitis.relapse of ulcerative colitis.
 The combination of VSL#The combination of VSL#33 plus mesalazineplus mesalazine
was slightly more effective than mesalazinewas slightly more effective than mesalazine
alone in mildalone in mild--toto--moderate ulcerative colitis.moderate ulcerative colitis.
 The combination of a prebiotic and a probioticThe combination of a prebiotic and a probiotic
( Bifidobacterium) was associated with( Bifidobacterium) was associated with
improvement in histologic scores and immuneimprovement in histologic scores and immune
activation in a oneactivation in a one--month randomizedmonth randomized
controlled trial.controlled trial.
 The following are illustrative controlled trials:The following are illustrative controlled trials:
 E. coli was as effective as lowE. coli was as effective as low--dosedose 55--
aminosalicylic acid (aminosalicylic acid (55--ASA) in preventingASA) in preventing
relapse of ulcerative colitis.relapse of ulcerative colitis.
 The combination of VSL#The combination of VSL#33 plus mesalazineplus mesalazine
was slightly more effective than mesalazinewas slightly more effective than mesalazine
alone in mildalone in mild--toto--moderate ulcerative colitis.moderate ulcerative colitis.
 The combination of a prebiotic and a probioticThe combination of a prebiotic and a probiotic
( Bifidobacterium) was associated with( Bifidobacterium) was associated with
improvement in histologic scores and immuneimprovement in histologic scores and immune
activation in a oneactivation in a one--month randomizedmonth randomized
controlled trial.controlled trial.

36. Maintaining remission of ulcerativeMaintaining remission of ulcerative
colitis withcolitis with Escherichia coli NissleEscherichia coli Nissle 19171917
Kruis et al., Gut. 2004 Nov;53(11):1617-23

37. Probiotics in Crohn's Disease
 Studies proved the preventive effect ofStudies proved the preventive effect of
Lactobacillus on the appearance of recurrentLactobacillus on the appearance of recurrent
lesions of CD after surgery.lesions of CD after surgery.
 Studies proved the preventive effect ofStudies proved the preventive effect of
Lactobacillus on the appearance of recurrentLactobacillus on the appearance of recurrent
lesions of CD after surgery.lesions of CD after surgery.

38.  A combination of three BifidobacteriumA combination of three Bifidobacterium
species, four Lactobacillus species has beenspecies, four Lactobacillus species has been
evaluated for the prevention of recurrentevaluated for the prevention of recurrent
inflammation after surgery.inflammation after surgery.
 After one year, there was a significantly lowerAfter one year, there was a significantly lower
rate of severe endoscopic recurrence in patientsrate of severe endoscopic recurrence in patients
treated with the antibiotic and probiotictreated with the antibiotic and probiotic
combination.combination.
 A combination of three BifidobacteriumA combination of three Bifidobacterium
species, four Lactobacillus species has beenspecies, four Lactobacillus species has been
evaluated for the prevention of recurrentevaluated for the prevention of recurrent
inflammation after surgery.inflammation after surgery.
 After one year, there was a significantly lowerAfter one year, there was a significantly lower
rate of severe endoscopic recurrence in patientsrate of severe endoscopic recurrence in patients
treated with the antibiotic and probiotictreated with the antibiotic and probiotic
combination.combination.

39. Probiotics and Pouchitis
 PouchitisPouchitis is a nonspecific inflammation of theis a nonspecific inflammation of the
ileal reservoir after ileoileal reservoir after ileo--anal anastomosis foranal anastomosis for
ulcerative colitis.ulcerative colitis.
 Disturbances in the intestinal micro flora mayDisturbances in the intestinal micro flora may
be the triggering factor in its pathogenesis.be the triggering factor in its pathogenesis.
 PouchitisPouchitis is a nonspecific inflammation of theis a nonspecific inflammation of the
ileal reservoir after ileoileal reservoir after ileo--anal anastomosis foranal anastomosis for
ulcerative colitis.ulcerative colitis.
 Disturbances in the intestinal micro flora mayDisturbances in the intestinal micro flora may
be the triggering factor in its pathogenesis.be the triggering factor in its pathogenesis.

40.  There is good evidence for the usefulness of
probiotics in preventing an initial attack of
pouchitis (VSL#3), and in preventing further
relapse of pouchitis after the induction of
remission with antibiotics.
 Probiotics can be recommended to patients
with pouchitis of mild activity, or as
maintenance therapy for those in remission.
 There is good evidence for the usefulness of
probiotics in preventing an initial attack of
pouchitis (VSL#3), and in preventing further
relapse of pouchitis after the induction of
remission with antibiotics.
 Probiotics can be recommended to patients
with pouchitis of mild activity, or as
maintenance therapy for those in remission.

41.  The SYNCAN study tested
the effect of oligofructoseoligofructose
plus two probiotic strainsplus two probiotic strains
in patients at risk of
developing colonic cancer.
 The results of the study
suggest that a synbiotic
preparation can decrease
the expression of
biomarkers for colorectal
cancer.
Colon cancer
 The SYNCAN study tested
the effect of oligofructoseoligofructose
plus two probiotic strainsplus two probiotic strains
in patients at risk of
developing colonic cancer.
 The results of the study
suggest that a synbiotic
preparation can decrease
the expression of
biomarkers for colorectal
cancer.

42. PROBIOTICS IN HEPATOLOGY
 A major aspect of liver disease is abnormal gutA major aspect of liver disease is abnormal gut
flora.flora.
 A balanced and healthy gut prevents a highA balanced and healthy gut prevents a high
percentage of pathological liver conditions.percentage of pathological liver conditions.
 The term “gut liver axis” has been used toThe term “gut liver axis” has been used to
suggest that the microflora affect the liver andsuggest that the microflora affect the liver and
acts as a cofactor in aetiology of chronic liveracts as a cofactor in aetiology of chronic liver
damage.damage.
 A major aspect of liver disease is abnormal gutA major aspect of liver disease is abnormal gut
flora.flora.
 A balanced and healthy gut prevents a highA balanced and healthy gut prevents a high
percentage of pathological liver conditions.percentage of pathological liver conditions.
 The term “gut liver axis” has been used toThe term “gut liver axis” has been used to
suggest that the microflora affect the liver andsuggest that the microflora affect the liver and
acts as a cofactor in aetiology of chronic liveracts as a cofactor in aetiology of chronic liver
damage.damage.

43.  Probiotic actions most relevant to liverProbiotic actions most relevant to liver
disease are modification of intestinal barrierdisease are modification of intestinal barrier
function and prevention of BT.function and prevention of BT.
 GramGram--negative BO, increased permeability,negative BO, increased permeability,
and impaired immunity all contribute toand impaired immunity all contribute to
increased BT, and there is a strongincreased BT, and there is a strong
correlation between the rate of BT and thecorrelation between the rate of BT and the
severity of cirrhosis.severity of cirrhosis.
 Probiotics might alter gut flora towardsProbiotics might alter gut flora towards
protective organisms and increase barrierprotective organisms and increase barrier
functionfunction
 Probiotic actions most relevant to liverProbiotic actions most relevant to liver
disease are modification of intestinal barrierdisease are modification of intestinal barrier
function and prevention of BT.function and prevention of BT.
 GramGram--negative BO, increased permeability,negative BO, increased permeability,
and impaired immunity all contribute toand impaired immunity all contribute to
increased BT, and there is a strongincreased BT, and there is a strong
correlation between the rate of BT and thecorrelation between the rate of BT and the
severity of cirrhosis.severity of cirrhosis.
 Probiotics might alter gut flora towardsProbiotics might alter gut flora towards
protective organisms and increase barrierprotective organisms and increase barrier
functionfunction

44. NAFLD
 Improved the hepatic
inflammatory,
steatotic, peroxidative
factors, serum
aminotransferase
Levels.
 (L. acidophilus, L.
bulgaricus)
 Improved the hepatic
inflammatory,
steatotic, peroxidative
factors, serum
aminotransferase
Levels.
 (L. acidophilus, L.
bulgaricus)

45. Alcoholic Liver Disease
 Improving the liver transaminases, total
bilirubin, ameliorating hepatic inflammation
and histological grade are results from
probiotic therapy

46.  Bacteriotherapy with probiotic in patients with
cirrhosis modulates bioecological system in the
intestinal tract via prevention of the growth of
pathogens, improvement to the mucosal layer,
preservation of intestinal epithelia cells, and BT
reduction.
 All of these mechanisms decrease portal
hypertension due to inhibition of NO production
 Incidence of HE, hospital admission, plasma-
ammonia level, serum bilirubin level
Cirrhosis
 Bacteriotherapy with probiotic in patients with
cirrhosis modulates bioecological system in the
intestinal tract via prevention of the growth of
pathogens, improvement to the mucosal layer,
preservation of intestinal epithelia cells, and BT
reduction.
 All of these mechanisms decrease portal
hypertension due to inhibition of NO production
 Incidence of HE, hospital admission, plasma-
ammonia level, serum bilirubin level

47. Hepatic Encephalopathy
 Evidence obtained from clinical trials suggest that
probiotics were able to decrease serum ammonia
levels and improve neuropsychological symptoms
 Possible mechanisms include:
 Reduction of bacterial urease activity
 Alleviation of pH and ammonia absorption
 Decreased intestinal permeability
 Evidence obtained from clinical trials suggest that
probiotics were able to decrease serum ammonia
levels and improve neuropsychological symptoms
 Possible mechanisms include:
 Reduction of bacterial urease activity
 Alleviation of pH and ammonia absorption
 Decreased intestinal permeability

48. Viral Hepatitis
 Loguerico et al. treated 20 patients with HCV
chronic hepatitis and 16 with HCV-related
cirrhosis withVSL#3 (Streptococcus thermophilus,
Bifidobacterium berve, Bifidobacterium longum,
Bifidobacterium infanti, Lactobacillus acidophilus,
Lactobacillus plantarum, Lactobacillus casei, and
Lactobacillus bulgaricus) for four months.
 ALT, and AST levels improved in two groups, and
gamma glutamyl transferase improvement was
observed only in HCV-related chronic hepatitis
group.
 Loguerico et al. treated 20 patients with HCV
chronic hepatitis and 16 with HCV-related
cirrhosis withVSL#3 (Streptococcus thermophilus,
Bifidobacterium berve, Bifidobacterium longum,
Bifidobacterium infanti, Lactobacillus acidophilus,
Lactobacillus plantarum, Lactobacillus casei, and
Lactobacillus bulgaricus) for four months.
 ALT, and AST levels improved in two groups, and
gamma glutamyl transferase improvement was
observed only in HCV-related chronic hepatitis
group.

49. Hepatocellular Carcinoma
 Studies were performed to assess probiotic
effects on toxicity of aflatoxin in liver
dysfunction and hepatocellular carcinoma.
 In a recent study (2012), diminution of aflatoxin
concentration was observed in fecal samples
after the administration of Lactobacillus rhamnosus
LC705
 Studies were performed to assess probiotic
effects on toxicity of aflatoxin in liver
dysfunction and hepatocellular carcinoma.
 In a recent study (2012), diminution of aflatoxin
concentration was observed in fecal samples
after the administration of Lactobacillus rhamnosus
LC705

50. Liver transplantation
 Infection in a postoperative period is usuallyInfection in a postoperative period is usually
very prevalent in patients who havevery prevalent in patients who have
undergone liver transplantation.undergone liver transplantation.
 The most causative agents involved in theseThe most causative agents involved in these
types of infections originate from thetypes of infections originate from the
digestive tract.digestive tract.
 Infection in a postoperative period is usuallyInfection in a postoperative period is usually
very prevalent in patients who havevery prevalent in patients who have
undergone liver transplantation.undergone liver transplantation.
 The most causative agents involved in theseThe most causative agents involved in these
types of infections originate from thetypes of infections originate from the
digestive tract.digestive tract.

51. Clinical Trials Assessed Probiotics Roles onClinical Trials Assessed Probiotics Roles on
Postoperative Infections in Liver TransplantationPostoperative Infections in Liver Transplantation
Four clinical trials performed on liver transplant patients
confirmed the inhibitory nature of probiotic
consumption on postoperative infections.

52. Probiotics to bind toxins and carcinogens
 Some experimental evidence suggests that
probiotics could be used to bind and immobilise
toxic compounds within the gut lumen.

53.  Through this process, the negative effects of
dietary toxins could be reduced and gut and
liver health improved. In vitro, L. rhamnosus
GG is able to bind mycotoxins known to
interfere with intestinal mucosal barrier.
 Through this process, the negative effects of
dietary toxins could be reduced and gut and
liver health improved. In vitro, L. rhamnosus
GG is able to bind mycotoxins known to
interfere with intestinal mucosal barrier.

54. PROBIOTICS IN TREATMENT OF
ALLERGY
1.1. Prevents food allergy by promotingPrevents food allergy by promoting
endogenous barrier mechanisms andendogenous barrier mechanisms and
alleviating intestinal inflammation.alleviating intestinal inflammation.
2.2. Reduction of serum IgEReduction of serum IgE levels leading tolevels leading to
improvement of cases of atopic dermatitis.improvement of cases of atopic dermatitis.
PROBIOTICS IN TREATMENT OF
ALLERGY
1.1. Prevents food allergy by promotingPrevents food allergy by promoting
endogenous barrier mechanisms andendogenous barrier mechanisms and
alleviating intestinal inflammation.alleviating intestinal inflammation.
2.2. Reduction of serum IgEReduction of serum IgE levels leading tolevels leading to
improvement of cases of atopic dermatitis.improvement of cases of atopic dermatitis.

55. Impact of Probiotics onImpact of Probiotics on
prevention of eczemaprevention of eczema
Wickenset et al. 2008. J Allergy Clin Immunol.
6 mo treatment of mother from 35 wks gestation to 6 months of age; infants
through 2 years of age

56. Probiotics as Immune Enhancers
 There is evidence that several probiotic strains
and the prebiotic oligofructose are useful in
boosting the immune response.

57.  Evidence was obtained in studies aimed at
preventing acute infectious disease
(nosocomial diarrhea in children, influenza
episodes in winter) and studies that tested
antibody responses to vaccines.
 Evidence was obtained in studies aimed at
preventing acute infectious disease
(nosocomial diarrhea in children, influenza
episodes in winter) and studies that tested
antibody responses to vaccines.

58. L. acidophilus NCFM and/or B. animalis BiL. acidophilus NCFM and/or B. animalis Bi--0707 reducesreduces
symptoms of colds/flusymptoms of colds/flu in Chinese childrenin Chinese children
..
 DBPC studyDBPC study
 N=N=326326 children (children (33––55 years ofyears of
age)age)
 Probiotic: NCFM orProbiotic: NCFM or
NCFM+BiNCFM+Bi--0707, dried powder, dried powder
mixed in milkmixed in milk
 Daily doseDaily dose 10101010cfu/dcfu/d
 66 months administrationmonths administration
 DBPC studyDBPC study
 N=N=326326 children (children (33––55 years ofyears of
age)age)
 Probiotic: NCFM orProbiotic: NCFM or
NCFM+BiNCFM+Bi--0707, dried powder, dried powder
mixed in milkmixed in milk
 Daily doseDaily dose 10101010cfu/dcfu/d
 66 months administrationmonths administration
Leyer et al. 2009. Pediatrics;124(2):e172-9

59. Lowering of Blood Cholesterol
 Animal studies have demonstrated the efficacy ofAnimal studies have demonstrated the efficacy of
some strains of LAB at being able tosome strains of LAB at being able to lowerlower
serum cholesterol levels, presumably by breakingserum cholesterol levels, presumably by breaking
down bile in the gut, thus inhibiting itsdown bile in the gut, thus inhibiting its
reabsorptionreabsorption ..

60. Reduction of Blood pressure
 Although not a confirmedAlthough not a confirmed
effect, some studies haveeffect, some studies have
indicated that consumption ofindicated that consumption of
milk fermented with variousmilk fermented with various
strains of LABstrains of LAB may result inmay result in
modest reductions in bloodmodest reductions in blood
pressure, an effectpressure, an effect possiblypossibly
related to the ACE inhibitorrelated to the ACE inhibitor--
like peptides produced duringlike peptides produced during
fermentationfermentation
 Although not a confirmedAlthough not a confirmed
effect, some studies haveeffect, some studies have
indicated that consumption ofindicated that consumption of
milk fermented with variousmilk fermented with various
strains of LABstrains of LAB may result inmay result in
modest reductions in bloodmodest reductions in blood
pressure, an effectpressure, an effect possiblypossibly
related to the ACE inhibitorrelated to the ACE inhibitor--
like peptides produced duringlike peptides produced during
fermentationfermentation

61. Vitamin production
 Probiotics have the capacity to synthesizeProbiotics have the capacity to synthesize
vitamins. In vitro studies and in humans havevitamins. In vitro studies and in humans have
documented the capacity ofdocumented the capacity of some probioticsome probiotic
strains to synthesize Vitamin k, folic Acid, andstrains to synthesize Vitamin k, folic Acid, and
BB1212..
 Probiotics have the capacity to synthesizeProbiotics have the capacity to synthesize
vitamins. In vitro studies and in humans havevitamins. In vitro studies and in humans have
documented the capacity ofdocumented the capacity of some probioticsome probiotic
strains to synthesize Vitamin k, folic Acid, andstrains to synthesize Vitamin k, folic Acid, and
BB1212..

62. Other uses of probioticsOther uses of probiotics
 Dental caries.
 Urinary Tract Infections
 Candida vaginal infections.
 Dental caries.
 Urinary Tract Infections
 Candida vaginal infections.

63. AVAILABLE FORMS
OF PROBIOTICS

64. Probiotic FoodsProbiotic Foods
YogurtYogurt
 UsuallyUsually mademade fromfrom milkmilk (rarely,(rarely, fromfrom cream)cream) inoculatedinoculated withwith
StreptococcusStreptococcus thermophilusthermophilus andand eithereither LactobacillusLactobacillus acidophilusacidophilus oror
LactobacillusLactobacillus bulgaricusbulgaricus..
 TurkishTurkish inin originorigin
 AvailableAvailable inin innumerableinnumerable formsforms andand flavorsflavors
11.. LowfatLowfat chocolatechocolate yogurtyogurt
22.. DrinkableDrinkable fruitfruit--flavoredflavored goatgoat yogurtyogurt
33.. NeonNeon--coloredcolored yogurtyogurt inin squeezesqueeze tubestubes
YogurtYogurt
 UsuallyUsually mademade fromfrom milkmilk (rarely,(rarely, fromfrom cream)cream) inoculatedinoculated withwith
StreptococcusStreptococcus thermophilusthermophilus andand eithereither LactobacillusLactobacillus acidophilusacidophilus oror
LactobacillusLactobacillus bulgaricusbulgaricus..
 TurkishTurkish inin originorigin
 AvailableAvailable inin innumerableinnumerable formsforms andand flavorsflavors
11.. LowfatLowfat chocolatechocolate yogurtyogurt
22.. DrinkableDrinkable fruitfruit--flavoredflavored goatgoat yogurtyogurt
33.. NeonNeon--coloredcolored yogurtyogurt inin squeezesqueeze tubestubes

65. FrozenFrozen
YogurtYogurt
LaLoo’s Goat’s MilkLaLoo’s Goat’s Milk
Frozen Yogurt,Frozen Yogurt,
naturally chocknaturally chock--full offull of
S. Thermophilus, L.S. Thermophilus, L.
Bulgaricus, L.Bulgaricus, L.
AcidophilusAcidophilus andand
Bifidus.Bifidus.
FrozenFrozen
YogurtYogurt
LaLoo’s Goat’s MilkLaLoo’s Goat’s Milk
Frozen Yogurt,Frozen Yogurt,
naturally chocknaturally chock--full offull of
S. Thermophilus, L.S. Thermophilus, L.
Bulgaricus, L.Bulgaricus, L.
AcidophilusAcidophilus andand
Bifidus.Bifidus.

66. JuiceJuice
 FirstFirst probioticprobiotic juicejuice launchedlaunched inin thethe fallfall ofof 20072007 byby NextNext
FoodsFoods..
 Goodbelly,Goodbelly, organicorganic fruitfruit juicejuice--basedbased probioticprobiotic beveragebeverage ,,
containscontains LL..PlantarumPlantarum 299299 hashas effectseffects onon irritableirritable bowelbowel
syndromesyndrome
 ThreeThree initialinitial flavorsflavors includeinclude BrilliantBrilliant Blueberry,Blueberry, PeachPeach
MangoMango andand StrawberryStrawberry RosehipRosehip

67. DairyDairy DrinkDrink
 Probiotic,Probiotic, culturedcultured dairydairy beveragebeverage
 HasHas citruscitrus flavorflavor
 SoldSold inin singlesingle--shotshot
containerscontainers thatthat containcontain aroundaround
88 billionbillion livelive andand activeactive LactobacillusLactobacillus
caseicasei ShirotaShirota cellscells perper bottlebottle
DairyDairy DrinkDrink
 Probiotic,Probiotic, culturedcultured dairydairy beveragebeverage
 HasHas citruscitrus flavorflavor
 SoldSold inin singlesingle--shotshot
containerscontainers thatthat containcontain aroundaround
88 billionbillion livelive andand activeactive LactobacillusLactobacillus
caseicasei ShirotaShirota cellscells perper bottlebottle

68. Rice YogurtRice Yogurt
An organic, nonAn organic, non--dairy, rice “yogurt” with whole grains and live,dairy, rice “yogurt” with whole grains and live,
active cultures, includingactive cultures, including Lactobacillus bulgaricus, StreptococcusLactobacillus bulgaricus, Streptococcus
thermophilus, Lactobacillus acidophilusthermophilus, Lactobacillus acidophilus andand BifidobacteriumBifidobacterium
bifidum.bifidum.

69. Chocolate barsChocolate bars
 AttuneAttune makesmakes WellnessWellness BarsBars inin threethree chocolatechocolate varietiesvarieties
andand threethree yogurtyogurt andand granolagranola varietiesvarieties..
 AllAll productsproducts containcontain “more“more thanthan 55 timestimes thethe livelive activeactive
culturescultures inin yogurt,yogurt, withwith lessless sugarsugar..
KashiKashi ViveVive ProbioticProbiotic DigestiveDigestive
WellnessWellness CerealCereal
ViveVive containscontains oneone billionbillion CFUsCFUs ofof
LactobacillusLactobacillus acidophilusacidophilus perper servingserving..
Chocolate barsChocolate bars
 AttuneAttune makesmakes WellnessWellness BarsBars inin threethree chocolatechocolate varietiesvarieties
andand threethree yogurtyogurt andand granolagranola varietiesvarieties..
 AllAll productsproducts containcontain “more“more thanthan 55 timestimes thethe livelive activeactive
culturescultures inin yogurt,yogurt, withwith lessless sugarsugar..
KashiKashi ViveVive ProbioticProbiotic DigestiveDigestive
WellnessWellness CerealCereal
ViveVive containscontains oneone billionbillion CFUsCFUs ofof
LactobacillusLactobacillus acidophilusacidophilus perper servingserving..

70. PROBIOTICPROBIOTIC
CANDYCANDY

71. Drug FormsDrug Forms
CapsulesCapsules
Powder blendsPowder blends
Chewable tabletsChewable tablets
CapsulesCapsules
Powder blendsPowder blends
Chewable tabletsChewable tablets

72. PROBIOTICS AVAILABLE INPROBIOTICS AVAILABLE IN
EGYPTEGYPT

73. ProbioticsProbiotics
DRAWBACKSDRAWBACKS

74. ProbioticsProbiotics
DRAWBACKSDRAWBACKS
 Not FDA regulated:Not FDA regulated:
Quality control is poorQuality control is poor
 Not FDA regulated:Not FDA regulated:
Quality control is poorQuality control is poor

75. 8080% of commercial preparations tested had% of commercial preparations tested had 11%%
or less of the bacterial concentration on theor less of the bacterial concentration on the
labellabel

76. ProbioticsProbiotics
DRAWBACKSDRAWBACKS
Numerous preparations on the market ?Numerous preparations on the market ?
 Which species is best?Which species is best?
 Are combination agents better?Are combination agents better?
 What is the appropriate dose?What is the appropriate dose?
 What is the appropriate duration ofWhat is the appropriate duration of
treatment?treatment?
Numerous preparations on the market ?Numerous preparations on the market ?
 Which species is best?Which species is best?
 Are combination agents better?Are combination agents better?
 What is the appropriate dose?What is the appropriate dose?
 What is the appropriate duration ofWhat is the appropriate duration of
treatment?treatment?

77. ProbioticsProbiotics
DRAWBACKSDRAWBACKS
 Probiotics taken orally can be destroyed byProbiotics taken orally can be destroyed by
the acidic conditions of the stomach.the acidic conditions of the stomach.
 Food forms should be kept in fridge.Food forms should be kept in fridge.
 To date, no generalisation can be made from
health effects of one probiotic strain to
another one and this remains a serious
problem within the probiotic research field
and its applications.
 Probiotics taken orally can be destroyed byProbiotics taken orally can be destroyed by
the acidic conditions of the stomach.the acidic conditions of the stomach.
 Food forms should be kept in fridge.Food forms should be kept in fridge.
 To date, no generalisation can be made from
health effects of one probiotic strain to
another one and this remains a serious
problem within the probiotic research field
and its applications.

78. ProbioticsProbiotics
DRAWBACKSDRAWBACKS
 Difficult to determine pathogenicity:Difficult to determine pathogenicity:
 Virulence factors for pathogensVirulence factors for pathogens
(adherence, colonization) are common(adherence, colonization) are common
in probiotic bacteria.in probiotic bacteria.
 The required dose of probiotics varyThe required dose of probiotics vary
greatly for different strains and thegreatly for different strains and the
specific desired health effect .specific desired health effect .
 May need several months of therapyMay need several months of therapy
to see an effect .to see an effect .
 Likely stop its action once discontinued.Likely stop its action once discontinued.
 Difficult to determine pathogenicity:Difficult to determine pathogenicity:
 Virulence factors for pathogensVirulence factors for pathogens
(adherence, colonization) are common(adherence, colonization) are common
in probiotic bacteria.in probiotic bacteria.
 The required dose of probiotics varyThe required dose of probiotics vary
greatly for different strains and thegreatly for different strains and the
specific desired health effect .specific desired health effect .
 May need several months of therapyMay need several months of therapy
to see an effect .to see an effect .
 Likely stop its action once discontinued.Likely stop its action once discontinued.

79. Side Effects of ProbioticsSide Effects of Probiotics
 Probitics are generally safe andProbitics are generally safe and
well tolerated.well tolerated.
 Rare cases reported bloating,Rare cases reported bloating,
flatulence, diarrhea, abdominalflatulence, diarrhea, abdominal
pain (pain (22%).%).
 People having on underlyingPeople having on underlying
disease or compromiseddisease or compromised
immune system cause potentialimmune system cause potential
health problems.health problems.
 Probitics are generally safe andProbitics are generally safe and
well tolerated.well tolerated.
 Rare cases reported bloating,Rare cases reported bloating,
flatulence, diarrhea, abdominalflatulence, diarrhea, abdominal
pain (pain (22%).%).
 People having on underlyingPeople having on underlying
disease or compromiseddisease or compromised
immune system cause potentialimmune system cause potential
health problems.health problems.

80. Invasivesive LactobacillusLactobacillus InfectionInfection
 Occasional reports ofOccasional reports of
invasive infectionsinvasive infections
 BacteremiaBacteremia
 skin rashskin rash
 feverfever
 bloody stoolsbloody stools
 EndocarditisEndocarditis
 Liver abscessLiver abscess
 Occasional reports ofOccasional reports of
invasive infectionsinvasive infections
 BacteremiaBacteremia
 skin rashskin rash
 feverfever
 bloody stoolsbloody stools
 EndocarditisEndocarditis
 Liver abscessLiver abscess

81.  Mostly reported in immunecompromisedMostly reported in immunecompromised
patients or uncontrolled medical disorders.patients or uncontrolled medical disorders.

82. Probiotics: What’s neededProbiotics: What’s needed
 Standardized protocolsStandardized protocols
 Larger studiesLarger studies
 Defined outcomesDefined outcomes
 Correlation with symptoms? Or cytokineCorrelation with symptoms? Or cytokine
levels? Or rectal biopsies? Or…levels? Or rectal biopsies? Or…
 Standardized protocolsStandardized protocols
 Larger studiesLarger studies
 Defined outcomesDefined outcomes
 Correlation with symptoms? Or cytokineCorrelation with symptoms? Or cytokine
levels? Or rectal biopsies? Or…levels? Or rectal biopsies? Or…

83. TAKE HOME MESSAGETAKE HOME MESSAGE
 Probiotics are living
microorganisms with multiple
mechanisms of action.
 Good safety profile
 Many beneficial effects in
gastroenterology, hepatology
and many other potential uses.
 Probiotics are living
microorganisms with multiple
mechanisms of action.
 Good safety profile
 Many beneficial effects in
gastroenterology, hepatology
and many other potential uses.

84. TAKE HOME MESSAGETAKE HOME MESSAGE
 to confirm the
viability of
probiotics, more
clinical trials in
various countries
with disparate
races, ethnicity, and
lifestyles would be
required.
 to confirm the
viability of
probiotics, more
clinical trials in
various countries
with disparate
races, ethnicity, and
lifestyles would be
required.

85. THANK YOU