title: Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources.
abstract: Dietary fibre sources are fermented by the gut flora to yield short-chain fatty acids (SCFA) together with degraded phytochemicals and plant nutrients. Butyrate, a major SCFA, is potentially chemoprotective by suppressing the growth of tumour cells and enhancing their differentiation. Conversely, it could lead to a positive selection pressure for transformed cells by inducing glutathione S-transferases (GST) and enhancing chemoresistance. Virtually nothing is known about how butyrate's activities are affected by other fermentation products. To investigate such interactions, a variety of dietary fibre sources was fermented with human faecal slurries in vitro, analysed for SCFA, and corresponding SCFA mixtures were prepared. HT29 colon tumour cells were treated for 72 h with individual SCFA or complex samples. The growth of cells, GST activity, and chemoresistance towards 4-hydroxynonenal were determined. Fermentation products inhibited cell growth more than the corresponding SCFA mixtures, and the SCFA mixtures were more active than butyrate, probably due to phytoprotectants and to propionate, respectively, which also inhibit cell growth. Only butyrate induced GST, whereas chemoresistance was caused by selected SCFA mixtures, but not by all corresponding fermentation samples. In summary, fermentation supernatant fractions contain compounds that: (1) enhance the anti-proliferative properties of butyrate (propionate, phytochemical fraction); (2) do not alter its capacity to induce GST; (3) prevent chemoresistance in tumour cells. It can be concluded that fermented dietary fibre sources are more potent inhibitors of tumour cell growth than butyrate alone, and also contain ingredients which counteract the undesired positive selection pressures that higher concentrations of butyrate induce in tumour cells.
authors.affiliation: Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Beyer-Sehlmeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Glei
authors.forename: Esther
authors.initials: E
authors.lastname: Hartmann
authors.forename: Rosin
authors.initials: R
authors.lastname: Hughes
authors.forename: Christoph
authors.initials: C
authors.lastname: Persin
authors.forename: Volker
authors.initials: V
authors.lastname: Böhm
authors.forename: Ian
authors.initials: I
authors.lastname: Rowland
authors.forename: Rainer
authors.initials: R
authors.lastname: Schubert
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahreis
authors.forename: Beatrice L
authors.initials: BL
authors.lastname: Pool-Zobel
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000382:microbiology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004043:Dietary Fiber / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005232:Fatty Acids, Volatile / Q000494:pharmacology; D005285:Fermentation / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans
chemical_list: D000447:Aldehydes; D002087:Butyrates; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; D006131:Growth Inhibitors; D005982:Glutathione Transferase; C027576:4-hydroxy-2-nonenal