Dietary Fiber, Prebiotics, &

Probiotics
Martin H. Floch,M.D.MACG,AGAF
Yale University
AGA Fellow's Nutrition Course - 2007
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MCROECOLOGY
Gut Secretions Microflora Foods
Gut Wall
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GUT WALL GUT WALL
W W HoIIow Lumen Organ HoIIow Lumen Organ
W W EpitheIiaI Lining Varies EpitheIiaI Lining Varies
at Each Organ at Each Organ
W W Mucous Layer Mucous Layer
Protective and Nurtures Protective and Nurtures
FIora FIora
W W Permits SeIective Permits SeIective
Absorption Absorption
W W HeIps ReguIate pH HeIps ReguIate pH
W W Integrity Affected by Integrity Affected by
Diet and FIora Diet and FIora
Definitions
W Dietary Fiber Nonstarch
polysaccharides of plant foods poorly
digested by human enzymes
W Prebiotics Nonstarch polysaccharide or
other substance supplements poorly
digested by human enzymes that nurture
probiotic organisms
W Probiotics human microorganisms fed as
supplements that benefit the host
Dietary Fiber Dietary Fiber
W W By chemicaI anaIysis fiber can be By chemicaI anaIysis fiber can be
broken into broken into soluble soluble and and insoluble insoluble
components (resistant starch identified by other chemicaI method) components (resistant starch identified by other chemicaI method)
W W $oluble $oluble components are pectic substances, some hemiceIIuIoses, components are pectic substances, some hemiceIIuIoses,
gums and muciIages and are compIeteIy fermented by the bacteriaI gums and muciIages and are compIeteIy fermented by the bacteriaI
fIora fIora
W W nsoluble nsoluble components are ceIIuIose, some hemiceIIuIoses, waxes, and components are ceIIuIose, some hemiceIIuIoses, waxes, and
Iignin primariIy in pIant ceII waIIs as weII as resistant starch are onIy Iignin primariIy in pIant ceII waIIs as weII as resistant starch are onIy
sIightIy fermented sIightIy fermented
W W eat eat is 90% insoIubIe and 10% soIubIe is 90% insoIubIe and 10% soIubIe
ats ats are 50% insoIubIe and 50% soIubIe are 50% insoIubIe and 50% soIubIe
Psyllium Psyllium 10% insoIubIe and 90% soIubIe 10% insoIubIe and 90% soIubIe
Dietary Fiber
Physiologic Properties
1. Slows transit in small bowel
2. Increases stool bulk
3. Holds on to water
4. Forms gels
5. Binds minerals and organic substances
6. Stimulates bacterial growth
7. Metabolized to SCFA
SCFA Production in Colon
Starch Bacterial Butyric (22)
+ Acetic (56)
Non-starch Enzymes Propionic(61)
Polysaccharides
DETARY FBER NTAKE
W Recommended intake 25-35 gm/day
W Actual intake 8 - 50 gm/day
1.Cereal content varies but bran is usually
cell wall.Examples- Raisen Bran -8gm.
Fiber One, and All Bran -12-14gm.
2.Fruits and vegetables vary and portion can
contain 2-5gm fiber [apple 2.8,beans
5,berries 5, potatoe 1.8]- fruits tend to be
> soluble and vegetable 50/50 sol/insol
3.Meats, fowl, fish, eggs and pure dairy
contain 0 fiber
Benefits of Dietary Fiber
W Large Literature on Benefits. Some Conflicts But General
Consensus s:
W ntake of greater than 25 to 35 gm/day associated with:
1. Prevention of Coronary Heart Disease and
Hyperlipidemia Control
2.Decrease Stroke in Males
3.Prevention and Treatment of Diabetes
4.Treatment of Dietary Constipation
5.Prevention and Treatment of Diverticular Disease
6.nverse Relationship with Colon Cancer Development
(AGA consensus)
Fiber in Cancer Prevention
W Numerous epidemiologic studies
W Prospective Decosse study in human
familial polyposis of the colon showed that
subjects on bran supplementation had less
polyp formation
W Animal studies show that Lactobacilli
degrade carcinogens.
W Bifidobacteria with and without prebiotics
decrease carcinogen activity and tumor
development in numerous animal studies.
PREBOTCS
Supplements not digested by human enzymes that
stimulate growth of beneficial bacteria
W Fructo-oligosaccharides
W nulin
W Galacto-,galactosyllactose-,xylo-,isomalto-and
soya oligosaccharides
W Pyrodextrins (glucose oligosaccharides)
W Lactulose
W Breast milk oligosaccharides
Oligosaccharides
W Usual pleasant slight sweet taste
W Add texture to foods
W Naturally occurs in artichoke, onion,garlic,
chicory, leek, and to a lesser degree in
cereals
W Raffinose and stachynose are major CHO
of beans and peas
W Commercially produced (FOS)
Benefits of Oligosaccharides
W Promote the growth of bifido-and
lactobacilli
W Lower colon pH
W Discourage growth of Clostridia
W Prevent constipation and diarrhea
W Have low glycemic index
W Water-soluble and of low viscosity
W Do not bind minerals
nulin
W Naturally occurs in fruits and vegetables
W Longer chain length than FOS
W Provides a fat mimicking texture when
added to food
W Now available in a supplement
Clinical use of Prebiotic nulin
W Constipation- 40g/d inulin for 19 days
increased bifidobacteria and produced soft
stools (Kleeson-AJCN,1997)
W BS- two studies- no significant effect
W BD- two Japan reports in open label
decreased symptoms.
W Controversial lipid lowering effect
W Main positive reports are increase in
bifidobacteria in infants by use of FOS
Bifidobacteria
W At least 4g/day of FOS are needed to
increase counts
W Effect increases with increased doses
W Ferment oligosaccharides to SCFA
W Produce B vitamins and some amino acids
W Restore flora after antibiotics
W nhibit the growth of pathogenic bacteria
Hepatic Encephalopathy
W Lactulose as a prebiotic alters the enteric
flora and successfully reduces
encephalopathy
W Lactobacillus acidophilus has also been
used and associated with a decrease in
urease and amino-acid-oxidase activity
Prebiotic Substances Available
Commercially
n USA
FOS (Ross),
Guar (Novartis)
Lactulose (Solvay and Bartek)
nulin (Fibersourse,P & G)
n Japan and Europe many of the other
oligosaccharides
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PROBOTCS
Lactobacillus acidophilus
Floch,Gastro Clin NA 2005;34:517 : Huebner Gastro Clin NA 2006 :35;355
Elie Metchnikoff
W 1845-1916 , Nobel Prize Winner
W Phagocytosis and Ageing
W ntoxication from the gut flora
W Putrefactive bacteria produced toxic substances
absorbed from the gut affecting the nervous and
vascular systems causing ageing
W His radical solution for autointoxication was
removal of the flora by colectomy
W Another approach was to replace putrefactive
bacteria with carbohydrate fermenting bacteria
PROBOTCS
W Live microbial food supplements which
beneficially affect the host animal by
improving its intestinal microbial balance.
W Usually strains of bacteria (lactobacilli or
bifidobacteria) or yeasts (Saccharomyces)
W Administered in yogurts or capsules
W Survive passage thru the gut
PROPERTES of PROBOTCS
W Human origin
W Resist upper G tract secretions
W Adhere to human intestinal cells
W Colonize the human intestinal tract
W Production of antimicrobial substances
W Antagonize carcinogenic/ pathogenic flora
W Safe in clinical use at > 10
10
W Stimulate immune process
W Fermentation
Probiotics Used in Human Studies
W Analysis of 186 published human studies [1980-2004]
W 171 controlled, 79 RDBPC (Montrose- JCG '05)
- 173* used single organism
- 82* used multiple organisms
- 84% reported significant benefit
W Most common used single are
L.acidophilus,L.reuteri,L.plantarum,L.GG, B.bacterium,
B.brevi, E.coli Nistle etc
W Most common multiple are combo of L.acidophilus &
Bifidobacterium.
W 'SL#3 has 8 organisms
Dose of Probiotic
W 'aries greatly with product
W Live and active cultureYogurts must
contain >10
8
[100 million]
W L.rhamnosus GG has 10 billion
W 'SL#3 has 300 to 450 billion per packet
W Common OTC have millions
DOSE
W n Crohn's Studies
W 12 billion organisms of L.rhamnosus GG did not
prevent recurrence post-op in placebo controlled
study
W 300 billion Saccharomyces were effective in
decreasing symptoms and preventing relapse in
placebo and mesalamine controlled studies
W 300 billion of eight organisms in 'SL#3 effective
in preventive post-op relapse.
Clinical Relevance *
W Excellent evidence A recommendation
W Studies mixed B recommendation
W Too little information C recommendation
*Floch. JClinGastro 2005;40:275
MMUNOREGULATON (A/B)
W ncrease gA production
W ncrease anti-rotaviral gA
W Production of gamma intereferon, TNF-
alph,L-1 by mononuclear cells incubated
with Lactobacillus.
W Adherant Lactobacilli and Bifidobacteria
significantly increase phagacytosis.
W Lactobacillus GG has been used to treat
cow milk allergy and atopic eczema
Treating nfection
Antibiotic AssociatedDiarrhea (A)
W Associated with C.difficile which may cause
pseudomembraneous colitis
W 3.2-29% of hospitalized patient
W Freeze dried lactobacillus not successful
W Lactobacillus GG successful in eradicating C.difficile
W Saccharomyces boulardii in DBC study reduced
recurrence from 22% to 9.5%
W BMJ 02 of nine studies revealed probiotics may prevent
C.difficile diarrhea
W Probiotics used in prevention and as adjuvant therapy in
AAD.
CHLDHOOD DARRHEA (A)
W Metanalysis revealed length of course
of childhood diarrhea reduced one day
when probiotic added to treatment
W Several species of lactobacilli effective
W B.bifidum reduces risk of diarrhea when
added to acidified milk or formula
TRA'ELLER'S DARRHEA (B)
W ncidence reduced from 71 to 43% in
tourist study with S.boulardii
Genitourinary (C)
W Recurrent Candida 'aginitis and Bacterial
'aginosis have been successfully treated by
administration of both oral and vaginal
Lactobacilli - 11 woman had 36 infections
compared to 11 woman who were on yogurt
who only had 4 infections.
W Recent RDBC study in 185 Nigerian woman
with vaginosis L.rhamnosus + L.reuteri +
metronidazole more effective than
metronidazole alone 88% to 40%*
*Anukum. Mic and nf. 2006
Probiotics in Pouchitis (A)
W Reduced counts of lacto-and bifidobacteria
-Gut '94
W Gionchetti et al - Gastroenteroogy '00
-random trial in 40 patients in remission
-6gm/day of 'SL#3 for 9 mo.
-300 billion org/gm of 8 strains
-20/20 controls but only 3/20 treated
relapse
W Oral probiotic therapy prevented relapse
Probiotic Use in BD (C)
W Ten controlled studies
W 3 in CUC, 4 in Crohn's, 3 in pouchitis
W 'aried organisms , varied doses
W CUC-E.coli Nissle effective in all three
W Crohn's-Saccharomyces effective in two
and 'SL#3 in one. L.GG ineffective in one.
W Pouchitis-'SL#3 effective in three
W Probiotics effective but in varing response
Probiotics in BS(C)
W Nobaek et al- AmJClin Gastro'00
random trial of 60 patients
400ml of 50million L.plantarium org/ml
L.plantarium recovered from feces
Decrease in flatulence and pain in treated
Symptoms difficult to measure but authors
feel strongly their results are significant
W Six other controlled studies published from
1985-2004. Three positive results and three
negative . 190 pts in six studies no conclusions
can be drawn. Larger controlled studies needed.
Lactobacillus and Bifidobacterium
in BS:
W Symptom response and cytokine profiles
L10 and L-12 dysregulated in BS
W L.salivarius,B.infantis,or placebo in malted
milk drink for eight weeks
W Probiotics recovered from stool
W B.infantis improved symptoms and L-10
increased with L-12 decreasing in BS
O'Mahoney-Gastroenterology-3/2005
Probiotic Organisms in USE
W Bifidobactor sp.
(bifidum, longum,
breve,animalis,
infantis,adolescentis)
W Streptoccus
thermophilus
W Saccharomyces
boulardii,cerevisiae
W Enerococcus faecium
W Lactobaciilli sp.
(casei, acidophilus,
bulgaricus, gaseri)
W L.rhamnosus, GG
W Lactococcus sp.
(lactis,cremaris)
CLAMS FOR PROBOTCS
W ncrease resistance to infection
W Decrease duration of diarrhea disease
W Stimulate immunity, modulate cytokine
gene expression, stimulate phagocytosis
W Beneficial effect on blood pressure,serum
cholesterol, diabetes mellitus,lactose
digestion and allergy
W Regression of tumors and reduction in
carcinogens
The Future
W Continued research to evaluate present
known organisms of the flora
W Engineered or alter organisms to create
desired immune or therapeutic response
(actococcus lactis secreting ovalbumin
induced specific tolerance - Gastroenterol
2007;133:517)
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Summary
W Microflora of the large intestine complete digestion
through fermentation, protect against pathogenic
bacteria and stimulate the immune system. Probiotics
and prebiotics(and fiber) in the diet can modify the
composition and some metabolic activities of the
microflora. Many claims for the potential benefits of
prebiotics remain unproved, whereas probiotics appear
effective in treatment of childhood diarrhea, post-
antibiotic diarrhea, and pouchitis. They affect immune
modulation and there are varied but encouraging results
in vaginosis, BS and BD,
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