PROBIOTCSPROBIOTCS

ByBy

Dr. Tarek ShetaDr. Tarek ShetaLecturer of internal medicineLecturer of internal medicine

Mansoura Faculty of MedicineMansoura Faculty of Medicine

First described byFirst described byMetchnikoff (a RussianMetchnikoff (a Russianscientist and professorscientist and professorat the Pasteur Instituteat the Pasteur Institutein Paris) inin Paris) in 19081908..“Live microbial food“Live microbial foodingredients that alteringredients that alterthe microflora andthe microflora andconfer health benefit”confer health benefit”

ProbioticsProbiotics First described byFirst described by

Metchnikoff (a RussianMetchnikoff (a Russianscientist and professorscientist and professorat the Pasteur Instituteat the Pasteur Institutein Paris) inin Paris) in 19081908..“Live microbial food“Live microbial foodingredients that alteringredients that alterthe microflora andthe microflora andconfer health benefit”confer health benefit”

PROBIOTICS (BACTERIOTHERAPY)PROBIOTICS (BACTERIOTHERAPY)FAO/WHO DefinitionFAO/WHO Definition

NonNon--pathogenic livingpathogenic livingorganisms that exert aorganisms that exert apositive influence on thepositive influence on thehealth of the host animal.health of the host animal.

Administered in both drugAdministered in both drugform and as components ofform and as components offoods and beverages.foods and beverages.

NonNon--pathogenic livingpathogenic livingorganisms that exert aorganisms that exert apositive influence on thepositive influence on thehealth of the host animal.health of the host animal.

Administered in both drugAdministered in both drugform and as components ofform and as components offoods and beverages.foods and beverages.

Prebiotics: definitionPrebiotics: definition

NonNon--digestible fooddigestible foodsupplements or ingredients.supplements or ingredients.

Not absorbed or degradedNot absorbed or degradedin the intestine.in the intestine.

NonNon--digestible fooddigestible foodsupplements or ingredients.supplements or ingredients.

Not absorbed or degradedNot absorbed or degradedin the intestine.in the intestine.

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 certainspecies of bacteria in the colon.species of bacteria in the colon.

OligosaccheridesOligosaccherides InulinInulin garlicgarlic onionsonions Asparagus,Asparagus, whole wheatwhole wheat Fiber supplementsFiber supplements

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.

Prebiotic vs ProbioticPrebiotic vs ProbioticPrebioticPrebiotic

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 broadereffects 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 broadereffects 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

Synbiotic = Probiotic + PrebioticSynbiotic = Probiotic + Prebiotic

SynbioticsSynbiotics A combination between a probioticA combination between a probiotic

organism in combination with itsorganism in combination with itsprebiotic food.prebiotic food.

Improves survivaImproves survivall and colonization byand colonization byprobioticsprobiotics..

More effective than probiotics aloneMore effective than probiotics alone..

A combination between a probioticA combination between a probioticorganism in combination with itsorganism in combination with itsprebiotic food.prebiotic food.

Improves survivaImproves survivall and colonization byand colonization byprobioticsprobiotics..

More effective than probiotics aloneMore effective than probiotics alone..

Characteristics of EffectiveCharacteristics of EffectiveProbioticsProbiotics

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 temporaryresidence in the intestineresidence in the intestine Import health benefitsImport health benefits

Characteristics of EffectiveCharacteristics of EffectiveProbioticsProbiotics

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 temporaryresidence in the intestineresidence in the intestine Import health benefitsImport health benefits

Different types of bacteria used asDifferent types of bacteria used asprobioticsprobiotics

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

Other speciesOther species

Escherichia coliEscherichia coli StreptococcusStreptococcus SaccharomycesSaccharomyces Several combinationsSeveral combinationson the marketon the market

Escherichia coliEscherichia coli StreptococcusStreptococcus SaccharomycesSaccharomyces Several combinationsSeveral combinationson the marketon the market

Clinical Effects are strainClinical Effects are strain--specificspecific

•• Different strains of the same species can beDifferent strains of the same species can bedifferent.different.

Potential Mechanisms of Action of ProbioticsPotential Mechanisms of Action of Probiotics

Levels of Probiotic ActivityLevels of Probiotic ActivityInterfere with

growth or survivalof bacteria in gut

lumen

Improve mucosalbarrier function and

mucosal immunesystem

Adapted from Rijkers GT, et al. J Nutr. 2010;140:671S-676S.

Improve mucosalbarrier function and

mucosal immunesystem

Affect systemicimmune system

CLINICAL APPLICATIONSOF PROBIOTICS

H. pyloriEradication

DiarrheaAcute infectiousAntibiotic-associatedC. difficile

IBDUlcerative colitisCrohn’s diseasePouchitis

Constipation

LactoseIntolerance

DiarrheaDiarrhea Treatment of acute diarrhea:

It has been confirmed that differentprobiotic strains are useful in reducingthe severity and duration of acuteinfectious diarrhea in children.

The evidence from studies on viralgastroenteritis is more convincing thanthe evidence on bacterial or parasiticinfections.

PROBIOTICS IN GI DISEASESDiarrheaDiarrhea

Treatment of acute diarrhea:It has been confirmed that different

probiotic strains are useful in reducingthe severity and duration of acuteinfectious diarrhea in children.

The evidence from studies on viralgastroenteritis is more convincing thanthe evidence on bacterial or parasiticinfections.

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 Diarrhea5 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..0505Duration of wateryDuration of waterydiarrheadiarrhea 3737 3838..11 00..9494Duration of fever (days)Duration of fever (days) 11..11 11..44 00..5959Diarrhea afterDiarrhea after 120120 hourshours 77 22 00..0303

V Rosenfeldt, et al. Pediatr Infect Dis J 21:417-9, 2002

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 isonly suggestive evidence thatLactobacillus GG, L. casei DN-114001, and S. boulardii are effective insome specific settings

RadiationRadiation--induced diarrheainduced diarrhea Traveller’s diarrhea. In the prevention of adult andadult and

childhood diarrheachildhood diarrhea, there isonly suggestive evidence thatLactobacillus GG, L. casei DN-114001, and S. boulardii are effective insome specific settings

Yogurt (Yogurt (364364)) Yogurt+Yogurt+L. caseiL. casei((360360))

PP--valuevalue

Children withChildren withdiarrheadiarrhea 8787 ((2222%)%) 6161 ((1616%)%) 00..029029

Prevention of Diarrheal IllnessPrevention of Diarrheal Illness18 Week Therapy in French Children (6-24 months) in Day Care

Children withChildren withdiarrheadiarrhea 8787 ((2222%)%) 6161 ((1616%)%) 00..029029Duration ofDuration ofdiarrhea (days)diarrhea (days) 33..9595 33..5353 00..2424Rotavirus positiveRotavirus positivestoolstool 22..22%% 00..33%%

CA Pedone, et al. Int J Clin Pract 54(9):568-71, 2000

AntibioticAntibiotic--associated diarrhea:associated diarrhea:

One study indicatedthat L. casei DN-114001 is effective inhospitalized adultpatients for preventingantibiotic-associateddiarrhea and C. difficilediarrhea.

One study indicatedthat L. casei DN-114001 is effective inhospitalized adultpatients for preventingantibiotic-associateddiarrhea and C. difficilediarrhea.

Probiotics for the Prevention ofProbiotics for the Prevention ofAntibiotic 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.

S. boulardii Is Effective in Patients withRecurrent C. difficile Disease

Initial CDD

CDD

recu

rren

ce, %

P=NS

Recurrent CDDP=0.04

CDD

recu

rren

ce, %

CDD=Clostridium difficile-associated diseaseMcFarland L, et al. JAMA. 1994;271:1913-1918.

CDD

recu

rren

ce, %

S. boulardii(n=31)

Placebo(n=33)

Control(n=34)

Patients received standard antibiotics (vancomycin or metronidazole) and S. boulardii 1 g/day or placebofor 4 weeks.

CDD

recu

rren

ce, %

S. boulardii(n=26)

Probiotics in C. Difficile-Associated Disease

RCTs of Probiotics for Treatmentof C. difficile Disease

BB=Bifidobacterium bifidum; LA=Lactobacillus acidophilus; LGG=Lactobacillusrhamnosus GG; LP=Lactobacillus plantarum 299v; SB=Saccharomyces boulardiiMacFarland LV. Am J Gastroenterol. 2006;101:812-822.

Eradication ofEradication ofHelicobacter pyloriHelicobacter pylori

Certain probiotics may be helpful asadjuvant therapy with antibiotics in theeradication of H. pylori infection.

Several lactobacilli and bifidobacterialstrains reduce the side effects ofantibiotic therapies and improve patientcompliance.

Certain probiotics may be helpful asadjuvant therapy with antibiotics in theeradication of H. pylori infection.

Several lactobacilli and bifidobacterialstrains reduce the side effects ofantibiotic therapies and improve patientcompliance.

A meta-analysis of 14 randomized trialssuggests that supplementation of anti–H.pylori antibiotic regimens with certainprobiotics may be effective in increasingeradication rates.

There is no evidence to support that aprobiotic alone, without concomitantantibiotic therapy, would be effective.

A meta-analysis of 14 randomized trialssuggests that supplementation of anti–H.pylori antibiotic regimens with certainprobiotics may be effective in increasingeradication rates.

There is no evidence to support that aprobiotic alone, without concomitantantibiotic therapy, would be effective.

Probiotics in irritable bowel syndrome(IBS)

IBS includes a range of symptoms, such asabdominal pain, altered bowel habits, bloatingand flatulence in the absence of structuralabnormalities in the intestine.

IBS includes a range of symptoms, such asabdominal pain, altered bowel habits, bloatingand flatulence in the absence of structuralabnormalities in the intestine.

Studies have observed alterations in intestinalmicroflora in patients and increased symptomsfollowing enteric infections, thereforeprobiotics might be a useful tool to improvesymptoms.

A reduction in abdominal bloating andflatulence as a result of probiotic treatments isa consistent finding in published studies; somestrains may ameliorate pain and provide globalrelief (B. infantis 35624). Lactobacillus reuterimay improve colicky symptoms within oneweek of treatment.

Studies have observed alterations in intestinalmicroflora in patients and increased symptomsfollowing enteric infections, thereforeprobiotics might be a useful tool to improvesymptoms.

A reduction in abdominal bloating andflatulence as a result of probiotic treatments isa consistent finding in published studies; somestrains may ameliorate pain and provide globalrelief (B. infantis 35624). Lactobacillus reuterimay improve colicky symptoms within oneweek of treatment.

Summary of Key Randomized ControlledSummary of Key Randomized ControlledTrials of Probiotics in IBSTrials of Probiotics in IBS

William D Chey, Reviews in Gastroenterol 2010

Probiotics after gut surgery

Roux-en Y gastric bypass surgery (one typeof bariatric surgery) is an effective treatmentof morbid obesity.

Problems that occur post operatively arealteration of microflora with bacterialovergrowth (BO) in the blind sac of theintestine, intestinal pain, and possiblyimpaired vitamin B12 status (due to lack ofintrinsic factor production from thestomach).

Roux-en Y gastric bypass surgery (one typeof bariatric surgery) is an effective treatmentof morbid obesity.

Problems that occur post operatively arealteration of microflora with bacterialovergrowth (BO) in the blind sac of theintestine, intestinal pain, and possiblyimpaired vitamin B12 status (due to lack ofintrinsic factor production from thestomach).

Probiotic treatment (6 mo)in 44 post operationalpatients. BO improvedonly after 6 mo, but notearlier.

Vitamin B12 statusimproved, gastrointestinalsymptoms remainedunchanged, but postoperational weight losswas significantly increasedin the probiotic group.

Probiotic treatment (6 mo)in 44 post operationalpatients. BO improvedonly after 6 mo, but notearlier.

Vitamin B12 statusimproved, gastrointestinalsymptoms remainedunchanged, but postoperational weight losswas significantly increasedin the probiotic group.

Lactose intolerance

Streptococcusthermophilus andLactobacillusdelbrueckii subsp.Bulgaricusimprove lactosedigestion andreduce symptomsrelated to lactoseintolerance.

Streptococcusthermophilus andLactobacillusdelbrueckii subsp.Bulgaricusimprove lactosedigestion andreduce symptomsrelated to lactoseintolerance.

Necrotizing enterocolitis

Probiotics supplementation reduces the riskof necrotizing enterocolitis in pretermneonates.

Systematic reviews of randomized controlledtrials have also shown a reduced risk ofdeath in probiotic treated groups.

Probiotics supplementation reduces the riskof necrotizing enterocolitis in pretermneonates.

Systematic reviews of randomized controlledtrials have also shown a reduced risk ofdeath in probiotic treated groups.

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.

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 preventingrelapse of ulcerative colitis.relapse of ulcerative colitis.

The combination of VSL#The combination of VSL#33 plus mesalazineplus mesalazinewas slightly more effective than mesalazinewas slightly more effective than mesalazinealone 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 withimprovement in histologic scores and immuneimprovement in histologic scores and immuneactivation in a oneactivation in a one--month randomizedmonth randomizedcontrolled 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 preventingrelapse of ulcerative colitis.relapse of ulcerative colitis.

The combination of VSL#The combination of VSL#33 plus mesalazineplus mesalazinewas slightly more effective than mesalazinewas slightly more effective than mesalazinealone 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 withimprovement in histologic scores and immuneimprovement in histologic scores and immuneactivation in a oneactivation in a one--month randomizedmonth randomizedcontrolled trial.controlled trial.

Maintaining remission of ulcerativeMaintaining remission of ulcerativecolitis withcolitis with Escherichia coli NissleEscherichia coli Nissle 19171917

Kruis et al., Gut. 2004 Nov;53(11):1617-23

Probiotics in Crohn's Disease

Studies proved the preventive effect ofStudies proved the preventive effect ofLactobacillus on the appearance of recurrentLactobacillus on the appearance of recurrentlesions of CD after surgery.lesions of CD after surgery.

Studies proved the preventive effect ofStudies proved the preventive effect ofLactobacillus on the appearance of recurrentLactobacillus on the appearance of recurrentlesions of CD after surgery.lesions of CD after surgery.

A combination of three BifidobacteriumA combination of three Bifidobacteriumspecies, four Lactobacillus species has beenspecies, four Lactobacillus species has beenevaluated for the prevention of recurrentevaluated for the prevention of recurrentinflammation after surgery.inflammation after surgery.

After one year, there was a significantly lowerAfter one year, there was a significantly lowerrate of severe endoscopic recurrence in patientsrate of severe endoscopic recurrence in patientstreated with the antibiotic and probiotictreated with the antibiotic and probioticcombination.combination.

A combination of three BifidobacteriumA combination of three Bifidobacteriumspecies, four Lactobacillus species has beenspecies, four Lactobacillus species has beenevaluated for the prevention of recurrentevaluated for the prevention of recurrentinflammation after surgery.inflammation after surgery.

After one year, there was a significantly lowerAfter one year, there was a significantly lowerrate of severe endoscopic recurrence in patientsrate of severe endoscopic recurrence in patientstreated with the antibiotic and probiotictreated with the antibiotic and probioticcombination.combination.

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 forulcerative colitis.ulcerative colitis.

Disturbances in the intestinal micro flora mayDisturbances in the intestinal micro flora maybe the triggering factor in its pathogenesis.be the triggering factor in its pathogenesis.

PouchitisPouchitis is a nonspecific inflammation of theis a nonspecific inflammation of theileal reservoir after ileoileal reservoir after ileo--anal anastomosis foranal anastomosis forulcerative colitis.ulcerative colitis.

Disturbances in the intestinal micro flora mayDisturbances in the intestinal micro flora maybe the triggering factor in its pathogenesis.be the triggering factor in its pathogenesis.

There is good evidence for the usefulness ofprobiotics in preventing an initial attack ofpouchitis (VSL#3), and in preventing furtherrelapse of pouchitis after the induction ofremission with antibiotics.

Probiotics can be recommended to patientswith pouchitis of mild activity, or asmaintenance therapy for those in remission.

There is good evidence for the usefulness ofprobiotics in preventing an initial attack ofpouchitis (VSL#3), and in preventing furtherrelapse of pouchitis after the induction ofremission with antibiotics.

Probiotics can be recommended to patientswith pouchitis of mild activity, or asmaintenance therapy for those in remission.

The SYNCAN study testedthe effect of oligofructoseoligofructoseplus two probiotic strainsplus two probiotic strainsin patients at risk ofdeveloping colonic cancer.

The results of the studysuggest that a synbioticpreparation can decreasethe expression ofbiomarkers for colorectalcancer.

Colon cancer The SYNCAN study tested

the effect of oligofructoseoligofructoseplus two probiotic strainsplus two probiotic strainsin patients at risk ofdeveloping colonic cancer.

The results of the studysuggest that a synbioticpreparation can decreasethe expression ofbiomarkers for colorectalcancer.

PROBIOTICS IN HEPATOLOGY

A major aspect of liver disease is abnormal gutA major aspect of liver disease is abnormal gutflora.flora.

A balanced and healthy gut prevents a highA balanced and healthy gut prevents a highpercentage 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 tosuggest that the microflora affect the liver andsuggest that the microflora affect the liver andacts as a cofactor in aetiology of chronic liveracts as a cofactor in aetiology of chronic liverdamage.damage.

A major aspect of liver disease is abnormal gutA major aspect of liver disease is abnormal gutflora.flora.

A balanced and healthy gut prevents a highA balanced and healthy gut prevents a highpercentage 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 tosuggest that the microflora affect the liver andsuggest that the microflora affect the liver andacts as a cofactor in aetiology of chronic liveracts as a cofactor in aetiology of chronic liverdamage.damage.

Probiotic actions most relevant to liverProbiotic actions most relevant to liverdisease are modification of intestinal barrierdisease are modification of intestinal barrierfunction 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 toincreased BT, and there is a strongincreased BT, and there is a strongcorrelation between the rate of BT and thecorrelation between the rate of BT and theseverity of cirrhosis.severity of cirrhosis.

Probiotics might alter gut flora towardsProbiotics might alter gut flora towardsprotective organisms and increase barrierprotective organisms and increase barrierfunctionfunction

Probiotic actions most relevant to liverProbiotic actions most relevant to liverdisease are modification of intestinal barrierdisease are modification of intestinal barrierfunction 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 toincreased BT, and there is a strongincreased BT, and there is a strongcorrelation between the rate of BT and thecorrelation between the rate of BT and theseverity of cirrhosis.severity of cirrhosis.

Probiotics might alter gut flora towardsProbiotics might alter gut flora towardsprotective organisms and increase barrierprotective organisms and increase barrierfunctionfunction

NAFLD Improved the hepatic

inflammatory,steatotic, peroxidativefactors, serumaminotransferaseLevels.

(L. acidophilus, L.bulgaricus)

Improved the hepaticinflammatory,steatotic, peroxidativefactors, serumaminotransferaseLevels.

(L. acidophilus, L.bulgaricus)

Alcoholic Liver Disease

Improving the liver transaminases, totalbilirubin, ameliorating hepatic inflammationand histological grade are results fromprobiotic therapy

Bacteriotherapy with probiotic in patients withcirrhosis modulates bioecological system in theintestinal tract via prevention of the growth ofpathogens, improvement to the mucosal layer,preservation of intestinal epithelia cells, and BTreduction.

All of these mechanisms decrease portalhypertension due to inhibition of NO production

Incidence of HE, hospital admission, plasma-ammonia level, serum bilirubin level

Cirrhosis

Bacteriotherapy with probiotic in patients withcirrhosis modulates bioecological system in theintestinal tract via prevention of the growth ofpathogens, improvement to the mucosal layer,preservation of intestinal epithelia cells, and BTreduction.

All of these mechanisms decrease portalhypertension due to inhibition of NO production

Incidence of HE, hospital admission, plasma-ammonia level, serum bilirubin level

Hepatic Encephalopathy

Evidence obtained from clinical trials suggest thatprobiotics were able to decrease serum ammonialevels 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 thatprobiotics were able to decrease serum ammonialevels and improve neuropsychological symptoms

Possible mechanisms include: Reduction of bacterial urease activity Alleviation of pH and ammonia absorption Decreased intestinal permeability

Viral Hepatitis Loguerico et al. treated 20 patients with HCV

chronic hepatitis and 16 with HCV-relatedcirrhosis withVSL#3 (Streptococcus thermophilus,Bifidobacterium berve, Bifidobacterium longum,Bifidobacterium infanti, Lactobacillus acidophilus,Lactobacillus plantarum, Lactobacillus casei, andLactobacillus bulgaricus) for four months.

ALT, and AST levels improved in two groups, andgamma glutamyl transferase improvement wasobserved only in HCV-related chronic hepatitisgroup.

Loguerico et al. treated 20 patients with HCVchronic hepatitis and 16 with HCV-relatedcirrhosis withVSL#3 (Streptococcus thermophilus,Bifidobacterium berve, Bifidobacterium longum,Bifidobacterium infanti, Lactobacillus acidophilus,Lactobacillus plantarum, Lactobacillus casei, andLactobacillus bulgaricus) for four months.

ALT, and AST levels improved in two groups, andgamma glutamyl transferase improvement wasobserved only in HCV-related chronic hepatitisgroup.

Hepatocellular Carcinoma

Studies were performed to assess probioticeffects on toxicity of aflatoxin in liverdysfunction and hepatocellular carcinoma.

In a recent study (2012), diminution of aflatoxinconcentration was observed in fecal samplesafter the administration of Lactobacillus rhamnosusLC705

Studies were performed to assess probioticeffects on toxicity of aflatoxin in liverdysfunction and hepatocellular carcinoma.

In a recent study (2012), diminution of aflatoxinconcentration was observed in fecal samplesafter the administration of Lactobacillus rhamnosusLC705

Liver transplantation

Infection in a postoperative period is usuallyInfection in a postoperative period is usuallyvery prevalent in patients who havevery prevalent in patients who haveundergone liver transplantation.undergone liver transplantation.

The most causative agents involved in theseThe most causative agents involved in thesetypes of infections originate from thetypes of infections originate from thedigestive tract.digestive tract.

Infection in a postoperative period is usuallyInfection in a postoperative period is usuallyvery prevalent in patients who havevery prevalent in patients who haveundergone liver transplantation.undergone liver transplantation.

The most causative agents involved in theseThe most causative agents involved in thesetypes of infections originate from thetypes of infections originate from thedigestive tract.digestive tract.

Clinical Trials Assessed Probiotics Roles onClinical Trials Assessed Probiotics Roles onPostoperative Infections in Liver TransplantationPostoperative Infections in Liver Transplantation

Four clinical trials performed on liver transplant patientsconfirmed the inhibitory nature of probioticconsumption on postoperative infections.

Probiotics to bind toxins and carcinogens

Some experimental evidence suggests thatprobiotics could be used to bind and immobilisetoxic compounds within the gut lumen.

Through this process, the negative effects ofdietary toxins could be reduced and gut andliver health improved. In vitro, L. rhamnosusGG is able to bind mycotoxins known tointerfere with intestinal mucosal barrier.

Through this process, the negative effects ofdietary toxins could be reduced and gut andliver health improved. In vitro, L. rhamnosusGG is able to bind mycotoxins known tointerfere with intestinal mucosal barrier.

PROBIOTICS IN TREATMENT OFALLERGY

1.1. Prevents food allergy by promotingPrevents food allergy by promotingendogenous barrier mechanisms andendogenous barrier mechanisms andalleviating intestinal inflammation.alleviating intestinal inflammation.

2.2. Reduction of serum IgEReduction of serum IgE levels leading tolevels leading toimprovement of cases of atopic dermatitis.improvement of cases of atopic dermatitis.

PROBIOTICS IN TREATMENT OFALLERGY

1.1. Prevents food allergy by promotingPrevents food allergy by promotingendogenous barrier mechanisms andendogenous barrier mechanisms andalleviating intestinal inflammation.alleviating intestinal inflammation.

2.2. Reduction of serum IgEReduction of serum IgE levels leading tolevels leading toimprovement of cases of atopic dermatitis.improvement of cases of atopic dermatitis.

Impact of Probiotics onImpact of Probiotics onprevention 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; infantsthrough 2 years of age

Probiotics as Immune Enhancers There is evidence that several probiotic strains

and the prebiotic oligofructose are useful inboosting the immune response.

Evidence was obtained in studies aimed atpreventing acute infectious disease(nosocomial diarrhea in children, influenzaepisodes in winter) and studies that testedantibody responses to vaccines.

Evidence was obtained in studies aimed atpreventing acute infectious disease(nosocomial diarrhea in children, influenzaepisodes in winter) and studies that testedantibody responses to vaccines.

L. acidophilus NCFM and/or B. animalis BiL. acidophilus NCFM and/or B. animalis Bi--0707 reducesreducessymptoms 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 powdermixed 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 powdermixed in milkmixed in milk

Daily doseDaily dose 10101010cfu/dcfu/d 66 months administrationmonths administration

Leyer et al. 2009. Pediatrics;124(2):e172-9

Lowering of Blood Cholesterol

Animal studies have demonstrated the efficacy ofAnimal studies have demonstrated the efficacy ofsome strains of LAB at being able tosome strains of LAB at being able to lowerlowerserum cholesterol levels, presumably by breakingserum cholesterol levels, presumably by breakingdown bile in the gut, thus inhibiting itsdown bile in the gut, thus inhibiting itsreabsorptionreabsorption ..

Reduction of Blood pressure

Although not a confirmedAlthough not a confirmedeffect, some studies haveeffect, some studies haveindicated that consumption ofindicated that consumption ofmilk fermented with variousmilk fermented with variousstrains of LABstrains of LAB may result inmay result inmodest reductions in bloodmodest reductions in bloodpressure, an effectpressure, an effect possiblypossiblyrelated to the ACE inhibitorrelated to the ACE inhibitor--like peptides produced duringlike peptides produced duringfermentationfermentation

Although not a confirmedAlthough not a confirmedeffect, some studies haveeffect, some studies haveindicated that consumption ofindicated that consumption ofmilk fermented with variousmilk fermented with variousstrains of LABstrains of LAB may result inmay result inmodest reductions in bloodmodest reductions in bloodpressure, an effectpressure, an effect possiblypossiblyrelated to the ACE inhibitorrelated to the ACE inhibitor--like peptides produced duringlike peptides produced duringfermentationfermentation

Vitamin production

Probiotics have the capacity to synthesizeProbiotics have the capacity to synthesizevitamins. In vitro studies and in humans havevitamins. In vitro studies and in humans havedocumented the capacity ofdocumented the capacity of some probioticsome probioticstrains to synthesize Vitamin k, folic Acid, andstrains to synthesize Vitamin k, folic Acid, andBB1212..

Probiotics have the capacity to synthesizeProbiotics have the capacity to synthesizevitamins. In vitro studies and in humans havevitamins. In vitro studies and in humans havedocumented the capacity ofdocumented the capacity of some probioticsome probioticstrains to synthesize Vitamin k, folic Acid, andstrains to synthesize Vitamin k, folic Acid, andBB1212..

Other uses of probioticsOther uses of probiotics

Dental caries. Urinary Tract Infections Candida vaginal infections.

Dental caries. Urinary Tract Infections Candida vaginal infections.

AVAILABLE FORMSOF PROBIOTICS

Probiotic FoodsProbiotic Foods

YogurtYogurt

UsuallyUsually mademade fromfrom milkmilk (rarely,(rarely, fromfrom cream)cream) inoculatedinoculated withwithStreptococcusStreptococcus thermophilusthermophilus andand eithereither LactobacillusLactobacillus acidophilusacidophilus ororLactobacillusLactobacillus bulgaricusbulgaricus..

TurkishTurkish inin originorigin

AvailableAvailable inin innumerableinnumerable formsforms andand flavorsflavors11.. LowfatLowfat chocolatechocolate yogurtyogurt22.. DrinkableDrinkable fruitfruit--flavoredflavored goatgoat yogurtyogurt33.. NeonNeon--coloredcolored yogurtyogurt inin squeezesqueeze tubestubes

YogurtYogurt

UsuallyUsually mademade fromfrom milkmilk (rarely,(rarely, fromfrom cream)cream) inoculatedinoculated withwithStreptococcusStreptococcus thermophilusthermophilus andand eithereither LactobacillusLactobacillus acidophilusacidophilus ororLactobacillusLactobacillus bulgaricusbulgaricus..

TurkishTurkish inin originorigin

AvailableAvailable inin innumerableinnumerable formsforms andand flavorsflavors11.. LowfatLowfat chocolatechocolate yogurtyogurt22.. DrinkableDrinkable fruitfruit--flavoredflavored goatgoat yogurtyogurt33.. NeonNeon--coloredcolored yogurtyogurt inin squeezesqueeze tubestubes

FrozenFrozenYogurtYogurt

LaLoo’s Goat’s MilkLaLoo’s Goat’s MilkFrozen Yogurt,Frozen Yogurt,

naturally chocknaturally chock--full offull ofS. Thermophilus, L.S. Thermophilus, L.

Bulgaricus, L.Bulgaricus, L.AcidophilusAcidophilus andandBifidus.Bifidus.

FrozenFrozenYogurtYogurt

LaLoo’s Goat’s MilkLaLoo’s Goat’s MilkFrozen Yogurt,Frozen Yogurt,

naturally chocknaturally chock--full offull ofS. Thermophilus, L.S. Thermophilus, L.

Bulgaricus, L.Bulgaricus, L.AcidophilusAcidophilus andandBifidus.Bifidus.

JuiceJuice

FirstFirst probioticprobiotic juicejuice launchedlaunched inin thethe fallfall ofof 20072007 byby NextNextFoodsFoods..

Goodbelly,Goodbelly, organicorganic fruitfruit juicejuice--basedbased probioticprobiotic beveragebeverage ,,containscontains LL..PlantarumPlantarum 299299 hashas effectseffects onon irritableirritable bowelbowelsyndromesyndrome

ThreeThree initialinitial flavorsflavors includeinclude BrilliantBrilliant Blueberry,Blueberry, PeachPeachMangoMango andand StrawberryStrawberry RosehipRosehip

DairyDairy DrinkDrink

Probiotic,Probiotic, culturedcultured dairydairy beveragebeverage

HasHas citruscitrus flavorflavor

SoldSold inin singlesingle--shotshotcontainerscontainers thatthat containcontain aroundaround88 billionbillion livelive andand activeactive LactobacillusLactobacilluscaseicasei ShirotaShirota cellscells perper bottlebottle

DairyDairy DrinkDrink

Probiotic,Probiotic, culturedcultured dairydairy beveragebeverage

HasHas citruscitrus flavorflavor

SoldSold inin singlesingle--shotshotcontainerscontainers thatthat containcontain aroundaround88 billionbillion livelive andand activeactive LactobacillusLactobacilluscaseicasei ShirotaShirota cellscells perper bottlebottle

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, Streptococcusthermophilus, Lactobacillus acidophilusthermophilus, Lactobacillus acidophilus andand BifidobacteriumBifidobacteriumbifidum.bifidum.

Chocolate barsChocolate bars

AttuneAttune makesmakes WellnessWellness BarsBars inin threethree chocolatechocolate varietiesvarietiesandand threethree yogurtyogurt andand granolagranola varietiesvarieties..

AllAll productsproducts containcontain “more“more thanthan 55 timestimes thethe livelive activeactiveculturescultures inin yogurt,yogurt, withwith lessless sugarsugar..

KashiKashi ViveVive ProbioticProbiotic DigestiveDigestiveWellnessWellness CerealCereal

ViveVive containscontains oneone billionbillion CFUsCFUs ofofLactobacillusLactobacillus acidophilusacidophilus perper servingserving..

Chocolate barsChocolate bars

AttuneAttune makesmakes WellnessWellness BarsBars inin threethree chocolatechocolate varietiesvarietiesandand threethree yogurtyogurt andand granolagranola varietiesvarieties..

AllAll productsproducts containcontain “more“more thanthan 55 timestimes thethe livelive activeactiveculturescultures inin yogurt,yogurt, withwith lessless sugarsugar..

KashiKashi ViveVive ProbioticProbiotic DigestiveDigestiveWellnessWellness CerealCereal

ViveVive containscontains oneone billionbillion CFUsCFUs ofofLactobacillusLactobacillus acidophilusacidophilus perper servingserving..

PROBIOTICPROBIOTICCANDYCANDY

Drug FormsDrug Forms

CapsulesCapsulesPowder blendsPowder blendsChewable tabletsChewable tablets

CapsulesCapsulesPowder blendsPowder blendsChewable tabletsChewable tablets

PROBIOTICS AVAILABLE INPROBIOTICS AVAILABLE INEGYPTEGYPT

ProbioticsProbioticsDRAWBACKSDRAWBACKS

ProbioticsProbioticsDRAWBACKSDRAWBACKS

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

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 thelabellabel

ProbioticsProbioticsDRAWBACKSDRAWBACKS

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?

ProbioticsProbioticsDRAWBACKSDRAWBACKS

Probiotics taken orally can be destroyed byProbiotics taken orally can be destroyed bythe 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 fromhealth effects of one probiotic strain toanother one and this remains a seriousproblem within the probiotic research fieldand its applications.

Probiotics taken orally can be destroyed byProbiotics taken orally can be destroyed bythe 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 fromhealth effects of one probiotic strain toanother one and this remains a seriousproblem within the probiotic research fieldand its applications.

ProbioticsProbioticsDRAWBACKSDRAWBACKS

Difficult to determine pathogenicity:Difficult to determine pathogenicity:Virulence factors for pathogensVirulence factors for pathogens

(adherence, colonization) are common(adherence, colonization) are commonin probiotic bacteria.in probiotic bacteria.

The required dose of probiotics varyThe required dose of probiotics varygreatly for different strains and thegreatly for different strains and thespecific desired health effect .specific desired health effect .

May need several months of therapyMay need several months of therapyto 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 commonin probiotic bacteria.in probiotic bacteria.

The required dose of probiotics varyThe required dose of probiotics varygreatly for different strains and thegreatly for different strains and thespecific desired health effect .specific desired health effect .

May need several months of therapyMay need several months of therapyto see an effect .to see an effect .

Likely stop its action once discontinued.Likely stop its action once discontinued.

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, abdominalpain (pain (22%).%).

People having on underlyingPeople having on underlyingdisease or compromiseddisease or compromisedimmune system cause potentialimmune system cause potentialhealth problems.health problems.

Probitics are generally safe andProbitics are generally safe andwell tolerated.well tolerated.

Rare cases reported bloating,Rare cases reported bloating,flatulence, diarrhea, abdominalflatulence, diarrhea, abdominalpain (pain (22%).%).

People having on underlyingPeople having on underlyingdisease or compromiseddisease or compromisedimmune system cause potentialimmune system cause potentialhealth problems.health problems.

Invasivesive LactobacillusLactobacillus InfectionInfection

Occasional reports ofOccasional reports ofinvasive infectionsinvasive infections BacteremiaBacteremia skin rashskin rash feverfever bloody stoolsbloody stools EndocarditisEndocarditis Liver abscessLiver abscess

Occasional reports ofOccasional reports ofinvasive infectionsinvasive infections BacteremiaBacteremia skin rashskin rash feverfever bloody stoolsbloody stools EndocarditisEndocarditis Liver abscessLiver abscess

Mostly reported in immunecompromisedMostly reported in immunecompromisedpatients or uncontrolled medical disorders.patients or uncontrolled medical disorders.

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…

TAKE HOME MESSAGETAKE HOME MESSAGE Probiotics are living

microorganisms with multiplemechanisms of action.

Good safety profile

Many beneficial effects ingastroenterology, hepatologyand many other potential uses.

Probiotics are livingmicroorganisms with multiplemechanisms of action.

Good safety profile

Many beneficial effects ingastroenterology, hepatologyand many other potential uses.

TAKE HOME MESSAGETAKE HOME MESSAGE

to confirm theviability ofprobiotics, moreclinical trials invarious countrieswith disparateraces, ethnicity, andlifestyles would berequired.

to confirm theviability ofprobiotics, moreclinical trials invarious countrieswith disparateraces, ethnicity, andlifestyles would berequired.

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