Background/aim-Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NF B), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this eVect by acting on proinflammatory cytokine expression. (Gut 2000;47:397-403) Methods-Intestinal

Background-Sodium butyrate, a product of colonic bacterial fermentation, is able to inhibit cell proliferation and to stimulate cell diVerentiation of colonic epithelial cell lines. It has been proposed that these cellular eVects could be linked to its ability to cause hyperacetylation of histone through the inhibition of histone deacetylase. Aim-To analyse the molecular mechanisms of butyrate action on cell proliferation/diVerentiation and to compare them with those of trichostatin A, a well known inhibitor of histone deacetylase. Methods-HT-29 cells were grown in the absence or presence of butyrate or trichostatin A. Cell proliferation and cell cycle distribution were studied after DNA staining by crystal violet and propidium iodide respectively. Cell cycle regulatory proteins were studied by western blot and reverse transcription-polymerase chain reaction. Cell diVerentiation was followed by measuring brush border enzyme activities. Histone acetylation was studied by acid/urea/Triton acrylamide gel electrophoresis. Results-Butyrate blocked cells mainly in the G 1 phase of the cell cycle, whereas trichostatin A was inhibitory in both G 1 and G 2 phases. Butyrate inhibited the mRNA expression of cyclin D1 without aVecting its protein expression and stimulated the protein expression of cyclin D3 without aVecting its mRNA expression. Trichostatin A showed similar eVects on cyclin D1 and D3. Butyrate and trichostatin A stimulated p21 expression both at the mRNA and protein levels, whereas their eVects on the expression of cyclin dependent kinases were slightly diVerent. Moreover, butyrate strongly stimulated the activity of alkaline phosphatase and dipeptidyl peptidase IV, whereas trichostatin A had no eVect. Finally, a six hour exposure to butyrate or trichostatin A induced histone H4 hyperacetylation. At 15 and 24 hours, histone H4 remained hyperacetylated in the presence of butyrate, whereas it returned to control levels in the presence of trichostatin A. Conclusions-The data may explain how butyrate acts on cell proliferation/ diVerentiation, and they show that trichostatin A does not reproduce every eVect of butyrate, mainly because of its shorter half life. (Gut 2000;46:507-514)

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The aim of the present study was to assess the relationship between the disappearance of dietary fibre sugars and the production of individual short-chain fatty acids (SCFA). The bacterial degradation of five dietary fibres whose sugars were quantified was investigated in vitro using a human faecal inoculum. Involvement of the main fibre sugars in SCFA production was evaluated by a stepwise multiple linear regression. The results show first that the nature and chiefly the associations between the fibre sugars were key variables in the fermentability. Second, the nature and the amounts of SCFA produced were closely related to the in vitro fermentation of the main sugars available: uronic acids seemed to be principally involved in the production of acetic acid whereas the production of propionic acid could be promoted by the fermentation of glucose and, to a lesser extent, by that of xylose and arabinose. Xylose tended to have a greater impact than uronic acids and glucose on the production of butyric acid. Thus, it would be possible to predict which SCFA could be specifically produced during the fermentation of a fibre, as far as the chemical composition and structure of this fibre are known.