title: Modulation of genotoxic enzyme activities by non-digestible oligosaccharide metabolism in in-vitro human gut bacterial ecosystems.
abstract: Supplementation of the human diet with prebiotic substances such as inulin and non-digestible oligosaccharides (NDO), e.g., galacto-oligosaccharides (GOS), has been associated with various health benefits. However, little information is available regarding the spatial location of their metabolism in human gut bacterial ecosystems. Therefore, the present study investigated the metabolism of inulin and GOS with respect to bacterial growth, bifidobacterial stimulatory properties and anti-mutagenicity potential, in a three-stage continuous culture model of the colon which reproduces the physicochemical characteristics of the proximal (V1) and distal (V2, V3) colons. Fermentation of both carbohydrates was rapid, and occurred primarily in V1, as evidenced by acid formation. Inulin metabolism was associated with 10-fold stimulation of lactobacillus populations, together with smaller increases in bifidobacterial cell counts in V1. However, peptostreptococci, enterococci and Clostridium perfringens also increased in this fermentation vessel. In contrast, GOS was only weakly bifidogenic in V1, although these bacteria did proliferate in V2. GOS also increased lactobacilli by an order of magnitude in V1. However, overall changes in microbial populations resulting from inulin or GOS addition were minimal in V2 and V3. Potential beneficial effects of inulin metabolism included minor reductions in beta-glucosidase and beta-glucuronidase, whereas GOS strongly suppressed these enzymes, together with arylsulphatase (AS). Growth of putatively health promoting micro-organisms was not only associated with reductions in enzymes linked to genotoxicity. For example, both carbohydrates stimulated synthesis of nitroreductase and azoreductase, throughout the fermentation system, while inulin increased AS. Colonic transit time is an important factor in bacterial metabolism in the large bowel, and these data suggest that, in some circumstances, NDO fermentation will occurprincipally in the proximal colon.
authors.forename: A J
authors.initials: AJ
authors.lastname: McBAIN
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL and *MRC Microbiology and Gut Biology Group, Level 6, Dundee University Medical School, Ninewells Hospital, Dundee DD1 9SY.
authors.forename: G T
authors.initials: GT
authors.lastname: Macfarlane
mesh_terms: D000328:Adult; D016587:Antimutagenic Agents / Q000378:metabolism; D001192:Arylsulfatases / Q000378:metabolism; D001419:Bacteria / Q000254:growth & development / Q000378:metabolism*; D001644:Bifidobacterium / Q000254:growth & development / Q000378:metabolism; D017753:Ecosystem; D005243:Feces / Q000201:enzymology / Q000382:microbiology; D005285:Fermentation; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007420:Intestine, Large / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D007444:Inulin / Q000378:metabolism*; D007777:Lactobacillaceae / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009601:Nitroreductases / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*; D019936:Probiotics / Q000378:metabolism; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; D009844:Oligosaccharides; D007444:Inulin; D009247:NADH, NADPH Oxidoreductases; D009601:Nitroreductases; C021106:azoreductase; D001192:Arylsulfatases; D001617:beta-Glucosidase; D005966:Glucuronidase