Dietary Fiber, Prebiotics,

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Dietary Fiber, Prebiotics, Probiotics

• Martin H. Floch,M.D.MACG,AGAF
• Yale University

AGA Fellows Nutrition Course - 2007
Aga fello
AGA
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MICROECOLOGY
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GUT WALL

• Hollow Lumen Organ
• Epithelial Lining Varies at Each Organ
• Mucous Layer Protective and Nurtures Flora
• Permits Selective Absorption
• Helps Regulate pH
• Integrity Affected by Diet and Flora

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Definitions

• Dietary Fiber Nonstarch polysaccharides of
  plant foods poorly digested by human enzymes
• Prebiotics Nonstarch polysaccharide or other
  substance supplements poorly digested by human
  enzymes that nurture probiotic organisms
• Probiotics human microorganisms fed as
  supplements that benefit the host

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Dietary Fiber

• By chemical analysis fiber can be
• broken into soluble and insoluble
• components (resistant starch identified by other
  chemical method)
• Soluble components are pectic substances, some
  hemicelluloses, gums and mucilages and are
  completely fermented by the bacterial flora
• Insoluble components are cellulose, some
  hemicelluloses, waxes, and lignin primarily in
  plant cell walls as well as resistant starch are
  only slightly fermented
• Wheat is 90 insoluble and 10 soluble
• Oats are 50 insoluble and 50 soluble
• Psyllium 10 insoluble and 90 soluble

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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
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SCFA Production in Colon

• Starch Bacterial Butyric
  (22)
• 
  Acetic (56)
• Non-starch Enzymes Propionic(61)
• Polysaccharides

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DIETARY FIBER INTAKE

• Recommended intake 25-35 gm/day
• 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 gt soluble and
  vegetable 50/50 sol/insol
• 3.Meats, fowl, fish, eggs and pure dairy contain
  0 fiber

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Benefits of Dietary Fiber

• Large Literature on Benefits. Some Conflicts But
  General Consensus Is
• Intake 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.Inverse Relationship with Colon Cancer
  Development
• (AGA consensus)

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Fiber in Cancer Prevention

• Numerous epidemiologic studies
• Prospective Decosse study in human familial
  polyposis of the colon showed that subjects on
  bran supplementation had less polyp formation
• Animal studies show that Lactobacilli degrade
  carcinogens.
• Bifidobacteria with and without prebiotics
  decrease carcinogen activity and tumor
  development in numerous animal studies.

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PREBIOTICS

• Supplements not digested by human enzymes that
  stimulate growth of beneficial bacteria
• Fructo-oligosaccharides
• Inulin
• Galacto-,galactosyllactose-,xylo-,isomalto-and
  soya oligosaccharides
• Pyrodextrins (glucose oligosaccharides)
• Lactulose
• Breast milk oligosaccharides

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Oligosaccharides

• Usual pleasant slight sweet taste
• Add texture to foods
• Naturally occurs in artichoke, onion,garlic,
  chicory, leek, and to a lesser degree in cereals
• Raffinose and stachynose are major CHO of beans
  and peas
• Commercially produced (FOS)

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Benefits of Oligosaccharides

• Promote the growth of bifido-and lactobacilli
• Lower colon pH
• Discourage growth of Clostridia
• Prevent constipation and diarrhea
• Have low glycemic index
• Water-soluble and of low viscosity
• Do not bind minerals

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Inulin

• Naturally occurs in fruits and vegetables
• Longer chain length than FOS
• Provides a fat mimicking texture when added to
  food
• Now available in a supplement

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Clinical use of Prebiotic Inulin

• Constipation- 40g/d inulin for 19 days increased
  bifidobacteria and produced soft stools
  (Kleeson-AJCN,1997)
• IBS- two studies- no significant effect
• IBD- two Japan reports in open label decreased
  symptoms.
• Controversial lipid lowering effect
• Main positive reports are increase in
  bifidobacteria in infants by use of FOS

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Bifidobacteria

• At least 4g/day of FOS are needed to increase
  counts
• Effect increases with increased doses
• Ferment oligosaccharides to SCFA
• Produce B vitamins and some amino acids
• Restore flora after antibiotics
• Inhibit the growth of pathogenic bacteria

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Hepatic Encephalopathy

• Lactulose as a prebiotic alters the enteric flora
  and successfully reduces encephalopathy
• Lactobacillus acidophilus has also been used and
  associated with a decrease in urease and
  amino-acid-oxidase activity

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Prebiotic Substances Available Commercially

• In USA
• FOS (Ross),
• Guar (Novartis)
• Lactulose (Solvay and Bartek)
• Inulin (Fibersourse,P G)
• In Japan and Europe many of the other
  oligosaccharides

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PROBIOTICS
Lactobacillus acidophilus
Floch,Gastro Clin NA 200534517 Huebner Gastro
Clin NA 2006 35355
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Elie Metchnikoff

• 1845-1916 , Nobel Prize Winner
• Phagocytosis and Ageing
• Intoxication from the gut flora
• Putrefactive bacteria produced toxic substances
  absorbed from the gut affecting the nervous and
  vascular systems causing ageing
• His radical solution for autointoxication was
  removal of the flora by colectomy
• Another approach was to replace putrefactive
  bacteria with carbohydrate fermenting bacteria

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PROBIOTICS

• Live microbial food supplements which
  beneficially affect the host animal by improving
  its intestinal microbial balance.
• Usually strains of bacteria (lactobacilli or
  bifidobacteria) or yeasts (Saccharomyces)
• Administered in yogurts or capsules
• Survive passage thru the gut

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PROPERTIES of PROBIOTICS

• Human origin
• Resist upper GI tract secretions
• Adhere to human intestinal cells
• Colonize the human intestinal tract
• Production of antimicrobial substances
• Antagonize carcinogenic/ pathogenic flora
• Safe in clinical use at gt 1010
• Stimulate immune process
• Fermentation

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Probiotics Used in Human Studies

• Analysis of 186 published human studies
  1980-2004
• 171 controlled, 79 RDBPC (Montrose- JCG 05)
• - 173 used single organism
• - 82 used multiple organisms
• - 84 reported significant benefit
• Most common used single are L.acidophilus,L.reute
  ri,L.plantarum,L.GG, B.bacterium, B.brevi, E.coli
  Nistle etc
• Most common multiple are combo of L.acidophilus
  Bifidobacterium.
• VSL3 has 8 organisms

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Dose of Probiotic

• Varies greatly with product
• Live and active cultureYogurts must contain gt108
  100 million
• L.rhamnosus GG has 10 billion
• VSL3 has 300 to 450 billion per packet
• Common OTC have millions

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DOSE

• In Crohns Studies
• 12 billion organisms of L.rhamnosus GG did not
  prevent recurrence post-op in placebo controlled
  study
• 300 billion Saccharomyces were effective in
  decreasing symptoms and preventing relapse in
  placebo and mesalamine controlled studies
• 300 billion of eight organisms in VSL3 effective
  in preventive post-op relapse.

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Clinical Relevance

• Excellent evidence A recommendation
• Studies mixed B recommendation
• Too little information C recommendation

Floch. JClinGastro 200540275
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IMMUNOREGULATION (A/B)

• Increase IgA production
• Increase anti-rotaviral IgA
• Production of gamma intereferon, TNF-alph,IL-1 by
  mononuclear cells incubated with Lactobacillus.
• Adherant Lactobacilli and Bifidobacteria
  significantly increase phagacytosis.
• Lactobacillus GG has been used to treat cow milk
  allergy and atopic eczema

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Treating Infection Antibiotic AssociatedDiarrhea
(A)

• Associated with C.difficile which may cause
  pseudomembraneous colitis
• 3.2-29 of hospitalized patient
• Freeze dried lactobacillus not successful
• Lactobacillus GG successful in eradicating
  C.difficile
• Saccharomyces boulardii in DBC study reduced
  recurrence from 22 to 9.5
• BMJ 02 of nine studies revealed probiotics may
  prevent C.difficile diarrhea
• Probiotics used in prevention and as adjuvant
  therapy in AAD.

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• CHILDHOOD DIARRHEA (A)
• Metanalysis revealed length of course of
  childhood diarrhea reduced one day when probiotic
  added to treatment
• Several species of lactobacilli effective
• B.bifidum reduces risk of diarrhea when added to
  acidified milk or formula
• TRAVELLERS DIARRHEA (B)
• Incidence reduced from 71 to 43 in tourist
  study with S.boulardii

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Genitourinary (C)

• Recurrent Candida Vaginitis and Bacterial
  Vaginosis 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.
• 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 Inf. 2006
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Probiotics in Pouchitis (A)

• Reduced counts of lacto-and bifidobacteria -Gut
  94
• Gionchetti et al - Gastroenteroogy 00
  -random trial in 40 patients in remission
  -6gm/day of VSL3 for 9 mo.
  -300 billion org/gm of 8 strains
  -20/20 controls but only 3/20 treated
  relapse
• Oral probiotic therapy prevented relapse

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Probiotic Use in IBD (C)

• Ten controlled studies
• 3 in CUC, 4 in Crohns, 3 in pouchitis
• Varied organisms , varied doses
• CUC-E.coli Nissle effective in all three
• Crohns-Saccharomyces effective in two and VSL3
  in one. L.GG ineffective in one.
• Pouchitis-VSL3 effective in three
• Probiotics effective but in varing response

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Probiotics in IBS(C)

• Nobaek et al- AmJClin Gastro00
• 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
• 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.

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Lactobacillus and Bifidobacterium in IBS

• Symptom response and cytokine profiles IL10 and
  IL-12 dysregulated in IBS
• L.salivarius,B.infantis,or placebo in malted milk
  drink for eight weeks
• Probiotics recovered from stool
• B.infantis improved symptoms and IL-10 increased
  with IL-12 decreasing in IBS

OMahoney-Gastroenterology-3/2005
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Probiotic Organisms in USE

• Bifidobactor sp. (bifidum, longum,
  breve,animalis, infantis,adolescentis)
• Streptoccus thermophilus
• Saccharomyces boulardii,cerevisiae
• Enerococcus faecium

• Lactobaciilli sp. (casei, acidophilus,
  bulgaricus, gaseri)
• L.rhamnosus, GG
• Lactococcus sp. (lactis,cremaris)

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CLAIMS FOR PROBIOTICS

• Increase resistance to infection
• Decrease duration of diarrhea disease
• Stimulate immunity, modulate cytokine gene
  expression, stimulate phagocytosis
• Beneficial effect on blood pressure,serum
  cholesterol, diabetes mellitus,lactose digestion
  and allergy
• Regression of tumors and reduction in carcinogens

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The Future

• Continued research to evaluate present known
  organisms of the flora
• Engineered or alter organisms to create desired
  immune or therapeutic response
• (Lactococcus lactis secreting ovalbumin
  induced specific tolerance - Gastroenterol
  2007133517)

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Summary

• 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, IBS and IBD,