Abstract
The hypothesis was studied that intestinal microbial metabolites play a role in the pathogenesis of inflammatory bowel disease. For that purpose, an in vitro model of the colon was inoculated with fresh feces of six healthy individuals and eight inflammatory bowel disease patients. Samples were taken from the model over time to analyze metabolites from both saccharolytic and proteolytic fermentation. Microbiotas from inflammatory bowel disease patients produced significantly more short-chain fatty acids and ammonia than microbiotas from healthy individuals. Furthermore, the branched-chain fatty acid production was 25% higher after inoculation with microbiotas from patients than after inoculation with microbiotas from healthy individuals. Phenolic compounds were produced by all microbiotas, with large interindividual variation. The production of (potentially toxic) metabolites may play a role in the onset or chronicity of inflammatory bowel disease, because they were produced in higher amounts by microbiotas from these patients than by microbiotas from healthy individuals.
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References
Elson CO: Commensal bacteria as targets in Crohn's disease. Gastroenterology 119:254-257, 2000
Raffi F, Ruseler-van Embden JGH, van Lieshout LMC: Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient with ulcerative colitis before and after antimicrobial treatments. Dig Dis Sci 44:637-642, 1999
Chiba M, Hoshina S, Kono M, Tobita M, Fukushima T, lizuka M, Wantanabe S: Staphylococcus aureus in inflammatory bowel disease. Scand J Gastroenterol 36:615-620, 2001
Gibson GR, MacFarlane GT: Human colonic bacteria: role in nutrition, physiology, and pathology. Boca Raton, FL, CRC Press, 1995
Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF: Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 115:1405-1413, 1998
Blaser MJ, Miller RA, Lacher J, Singleton JW: Patients with active Crohn's disease have elevated serum antibodies to antigens of seven enteric bacterial pathogens. Gastroenterol 87:888-894, 1984
Harris JE, Lammerding AM: Crohn's disease and Mycobacterium avium subsp. paratuberculosis: current issues. J Food Prot 64:2103-2110, 2001
MacFarlane GT, Gibson GR, Cummings JH: Comparison of fermentation reactions in different regions of the human colon. J Appl Bacteriol 72:57-64, 1992
Cummings JH: The Large Intestine in Nutrition and Disease. Bruxelles, Institut Danone, 1997
Gottschalk G: Bacterial fermentation. In Bacterial Metabolism. New York, Springer-Verlag, 1986, pp 210-282
Salminen S, Bouly C, Boutron-Ruault M-C, Cummings JH, Franck A, Gibson GR, Isolauri E, Moreau M-C, Roberfroid MB, Rowland IR: Functional food science and gastrointestinal physiology and function. Br J Nutr 80:S147-S171, 1998
Alles MS, Hartemink R, Meyboom S, Harryvan JL, van Laere KMJ, Nagengast FM, Hautvast JGAJ: Effect of transgalactooligosaccharides on the composition of the human intestinal microflora and on putative risk markers for colon cancer. Am J Clin Nutr 69:980-991, 1999
Wrong OM: Bacterial metabolism of protein and endogenous nitrogen compounds. In Role of the Gut Flora in Toxicity and Cancer. Rowland IR (ed). London, Academic Press, 1988, pp 227-262
Smith EA, MacFarlane GT: Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. Microb Ecol 33:180-188, 1997
Roedinger WEW, Duncan A: Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology 104:802-809, 1993
Jorgensen J, Mortensen PB: Hydrogen sulfide and colonic epithelial metabolism—Implications for ulcerative colitis. Dig Dis Sci 46:1722-1732, 2001
Jacobasch G, Schmiedl D, Kruschewski M, Schmehl K: Dietary resistant starch and chronic inflammatory bowel diseases. Int J Colorectal Dis 14:201-211, 1999
Fiocchi C: Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115:182-205, 1998
MacFariane GT: Fermentation reactions in the large intestine. In Short-Chain Fatty Acids: Metabolism and Clinical Importance. Report of the Tenth Ross Conference on Medical Research. Roche AF (ed). Columbus, OH, Ross Laboratories, 1991, pp 5-10
Chadwick VS, Anderson RP: Microorganism and their products in inflammatory bowel disease. In Inflammatory Bowel Disease. MacDermott, RP (ed). New York, Elsevier, 1992, pp 241-258
Gibson GR, Cummings JH, MacFariane GT: Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria. Appl Environ Microbiol 54:2750-2755, 1988
Minekus M, Smeets-Peeters M, Bernalier A, Marol-Bonnin S, Havenaar R, Marteau P, Alric M, Fonty G, Huis in 't Veld JHJ: A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl Microbiol Biotechnol 53:108-114, 1999
Venema K, van Nuenen HMC, Smeets-Peeters M, Minekus M, Havenaar R: TNO's in vitro large intestinal model: an excellent screening tool for functional food and pharmaceutical research. Ernährung/Nutrition 24:558-564, 2000
Jouany JP: Volatile fatty acids and alcohols determination in digestive contents, silage juice, bacterial culture and anaerobic fermenter contents. Sci Aliments 2:131-144, 1982
Yoshihara I: Gas chromatographic detection of volatile phenols and microdetermination of p-cresol in gastrointestinal contents of domestic animals. Agr Biol Chem 42:1607-1609, 1978
Yoshihara I: Simultaneous gas chromatographic microdetermination of indole, skatole, and p-cresol in gastrointestinal contents of domestic animals. Agr Biol Chem 43:1985-1987, 1979
Yoshihara I: Gas chromatographic rapid microdetermination of urinary volatile phenols. Agr Biol Chem 44:1185-1187, 1980
Phenols according to EPA method 8040. Application note 912. Chrompack Chromatography catalog, GC applications, Bergen op Zoom, Chrompack Nederland, 1997
Cummings JH, Roberfroid MB, Andersson H, Barth C, Ferro-Luzzi A, Ghoos Y, Gibney M, Hermonsen K, James WPT, Korver O, Lairon D, Pascal G, Voragen AGS: A new look at dietary carbohydrate: chemistry, physiology and health. Eur J Clin Nutr 51:417-423, 1997
Cummings JH and MacFarlane GT: The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 70:443-459, 1991
Ruseler-van Embden JGH, Schouten WR, van Lieshout LMC: Pouchitis: result of microbial imbalance? Gut 35:658-664, 1994
Cummings JH, Englyst HN: Fermentation in the large intestine and the available substrates. Am J Clin Nutr 45:1243-1255, 1987
Cummings JH, Gibson GR, MacFarlane GT: Quantitative estimates of fermentation in the hind gut of man. Acta Vet Scan Suppl 86:76-82, 1989
Van Nuenen HMC, Meyer PD, Venema K: The effect of various inulins and Clostridium difficile on the metabolic activity of the human colonic microbiota in vitro. Microbial Ecology in Health and Disease 15(2–3):137-144, 2003
Venema K, Van Nuenen HMC, Van den Heuvel EG, Pool W, Van der Vossen JMBM: The effect of lactulose on the composition of the intestinal microbiota and short-chain fatty acid production in human volunteers and a computer-controlled model of the proximal large intestine. Microbial Ecology in Health and Disease 15(2–3):94-105, 2003
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Van Nuenen, M.H.M.C., Venema, K., Van Der Woude, J.C.J. et al. The Metabolic Activity of Fecal Microbiota from Healthy Individuals and Patients with Inflammatory Bowel Disease. Dig Dis Sci 49, 485–491 (2004). https://doi.org/10.1023/B:DDAS.0000020508.64440.73
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DOI: https://doi.org/10.1023/B:DDAS.0000020508.64440.73