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Supplement: Nutrition and Gene Regulation

Short Chain Fatty Acid Regulation of Signaling Genes Expressed by the Intestinal Epithelium

Professor of Paediatric Gastroenterology, Centre for Adult & Paediatric Gastroenterology, Institute of Cell and Molecular Science, Barts and the London, Queen Mary, University of London, London, UK

²To whom correspondence should be addressed. E-mail: i.r.sanderson{at}.qmul.ac.uk.

Changes in diet greatly affect the mucosal immune system, particularly in diseases such as Crohn’s disease and necrotizing enterocolitis. This review examines the hypothesis that alterations in the luminal environment of the intestine regulate the expression of genes in the epithelium responsible for signaling to immune cells. Increasing chemokine expression in the mouse intestinal epithelium using transgenic techniques enhances the recruitment of neutrophils and lymphocytes into the intestine. Furthermore, SCFA concentrations in the intestinal lumen vary markedly with diet. SCFAs alter chemokine expression by inhibiting histone deacetylase activity in the enterocyte. The review therefore describes a molecular pathway explaining how changes in diet may alter leukocyte recruitment by regulating enterocyte gene expression. It is likely that other similar pathways remain to be discovered.

KEY WORDS: • intestine • epithelium • butyrate • chemokine • gene expression • histone acetylation

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