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Prebiotics, Probiotics, & Antibiotics: Controversies in the .

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Slide 1 :

Prebiotics, Probiotics, & Antibiotics: Controversies in the Treatment of IBS Brian E. Lacy, Ph.D., M.D. Associate Professor of Medicine Dartmouth Medical School Director, GI Motility Laboratory Dartmouth-Hitchcock Medical Center

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Disclosure Investigator Initiated Research Support: AstraZeneca, GlaxoSmithKline, Medtronics, Novartis, Prometheus Speaker’s Bureau: Novartis, Takeda

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Goals Define commonly used terms Review the microecology of the intestinal tract Discuss the mechanism of action of probiotics Review the available literature on probiotics and IBS Assess the role of antibiotics in the treatment of IBS

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Functional Foods Functional foods – substances or supplements administered to obtain a specific result Also called “nutriceuticals” or “biotherapeutics” Examples: Prebiotics Probiotics

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Prebiotics Non-digestible food supplements or ingredients Not absorbed or degraded Alter the balance of intestinal flora and by acting as substrates stimulate the growth of beneficial bacteria (i.e., Lactobacillus and Bifidobacteria)

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Prebiotics Fructooligosaccharide (aka oligofructose) Isomaltooligosaccharide Xylooligosaccharide Inulin Fiber Oligomate Palatinose Pyrodextrin Raftiline

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Probiotics Non-pathogenic live microbial food supplements Organisms that, when administered in adequate amounts, exert a positive influence on the health of the host animal Live organisms that benefit the host animal by improving intestinal microbial balance Usually administered in yogurt or capsules

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A Brief History of Probiotics Metchnikoff – 1907 – ingesting yogurt with Lactobacilli reduces toxic bacteria of the gut and prolongs life Kipeloff – 1926 – stressed importance of Lactobacillus acidophilus for good health Rettger – 1930’s – early clinical application of Lactobacillus Parker – 1974 – 1st to use the term probiotics Fuller – 1989 – defined probiotics

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Probiotics Lactobacilli – anerobic, gram (+) rods casei plantarum acidophilus reuteri Bifidobacteria – anerobic, gram (+) rods VSL #3 (8 separate organisms: 3 Bifidobacteria, 1 Streptococcus, 4 Lactobacilli) Enterococcus Streptococcus salivarius Saccharomyces

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How is normal mucosal immune function maintained? GI secretions (saliva, acid, bile) Mucus Normal peristalsis (presence of MMC) Barrier function (tight junctions) Intestinal proteolysis Intestinal immune cells IgA production and secretion

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Intestinal Microecology Foods that enter the GI Tract

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Intestinal Flora: A symbiotic relationship with the host Human GI tract contains 10x more bacteria (1014) than eukaryotic cells in the body Protects the host Stimulates immune function Produces antimicrobial substances Trophic effect on intestinal epithelium Maintains the enterohepatic circulation of bile acids Involved in metabolic processes (i.e., fermentation) in the colon

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Intestinal Microflora: Location & Prevalence Rare in the esophagus Uncommon in the stomach primarily gram (+) 102 - 104 105 in the jejunum – primarily aerobes 1010 – 1012 in the colon primarily anerobes 1000x more anerobes than aerobes

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Formation & Maintenance of Gut Flora (Microbiota) Genetic factors Age Gender Mother’s microbiology Mode of delivery Feeding practices Breast-fed – Bifidobacterium Bottle-fed - Lactobacillus Co-morbid conditions Medications Diet

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Predominant human fecal flora Aerobic organisms E. coli Enterococcus sp. Streptococcus sp. Bacillus sp. Citrobacter sp. Klebsiella sp. Anaerobic species Anaerobic cocci Bacteroides sp. Eubacterium sp. Bifidobacterium sp. Lactobacillus sp. Fusobacterium sp. Clostridium sp.

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Conditions that can disrupt normal gut flora homeostasis Medications Antibiotics Surgery Radiation Diet Co-morbid diseases Crohn’s Scleroderma

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Probiotics: An Overview Key properties Mechanisms of action Potential uses

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Key Properties of Probiotics Bacteria of human origin Safe to use in large amounts in clinical practice Resist secretions of the upper GI tract Survive passage through the GI tract Adhere to human intestinal cells

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Key Properties of Probiotics Able to colonize the lumen of the GI tract Help to protect the cells against invasion by pathogens Produce antimicrobial substances hydrogen peroxide organic acids bacteriocins Antagonize carcinogenic and pathogenic flora

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Probiotics: Mechanism of Action Competitive inhibition Barrier protection Immune effects Anti-inflammatory effects Production of various substances (enzymes, SCFA, bacteriocidal agents) Ability to alter local pH and physiology Provides nutrition to colonocytes

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Probiotics: Competitive Inhibition Helps to restore the balance of “good” bacteria and “bad” bacteria Facilitates the growth of healthy bacteria – i.e., Bifidobacterium and Lactobacillus Bifidobacterium infantis inhibits the growth of Salmonella (O’Mahony 2004; Gastro)

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Probiotics: Barrier Protection Intestinal permeability to bacteria is increased with inflammation, i.e., Crohn’s, UC, ischemia (Nejdfors et al Scan J Gastroenterol 1998) Pretreatment with L. plantarum 299v inhibits E. coli intestinal permeability (Mangell et al Dig Dis Sci 2002) B. infantis prevents bacterial (Salmonella) translocation (O’Mahony Gastro 2004)

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Probiotics & Immune Function Mononuclear cells incubated with Lactobacilli produce higher levels of IFN-gamma, TNF-alpha, and IL-1 (MacFarlane & Cummings, BMJ, 1999) Bifidobacteria suppressed the pro-inflammatory mediators (TNF-alpha, IFN-gamma, IL-12) in a murine model of IBD (IL-10 knockout) (McCarthy et al, Gut 2003) In healthy volunteers, L. rhamnosus increased phagocytic activity and NK tumor cell killing activity (Sheih et al, J Am Coll Nutri 2001)

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Probiotics & Immune Function Borruel and colleagues assayed ileal specimens from Crohn’s patients (10) and compared to 5 controls (right hemicolectomy for colon cancer) Specimens cultured with various bacteria (L. casei, L. bulgaricus, L. crispatus) CD4 levels and TNF-alpha levels reduced in Crohn’s explants but not in normal volunteers Impression: probiotics interact with immunocompetent cells to modulate the production of pro-inflammatory cytokines from ileal tissue in Crohn’s patients (Borruel Gut 2002)

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Probiotics: Production of Other Substances Intestinal bacteria play a key role in the production of short-chain fatty acids (SCFA) Butyric acid is the main fuel for colonocytes L. plantarum appeared to increase production of butyric acid in 36 healthy volunteers, leading to reductions in fibrinogen, leptin, and monocyte adhesive properties (Naruszewicz et al Am J Clin Nutr 2002)

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Probiotics: Impact on Local Physiology Example - Antibiotic associated diarrhea Restores resident flora Increases production of SCFA SFCAs are absorbed by diffusion, leading to increased water and Na absorption Stimulates colonocyte proliferation, which may further improve water and Na reabsorption

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Probiotics: Potential Uses IBS IBD Infectious diarrhea in children (i.e., rotavirus) Traveler’s diarrhea Antibiotic associated diarrhea Clostridium difficile

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	SlidesOnline 1 Years ago. Category: other

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Chaudary & Truelove – 1962 – described onset of IBS after dysentery; McKendall & Read – 1994IBS pat more Chaudary & Truelove – 1962 – described onset of IBS after dysentery; McKendall & Read – 1994IBS patients may have different ratios of normal gut flora ... less

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