Bacterial Metabolite Indole Modulates Incretin Secretion from Intestinal Enteroendocrine L Cells

• Published in: Cell reports (Cambridge) 2014-11, Vol.9 (4), p.1202-1208
• Main Authors: Chimerel, Catalin, Emery, Edward, Summers, David K., Keyser, Ulrich, Gribble, Fiona M., Reimann, Frank
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adenosine Diphosphate - metabolism; Adenosine Triphosphate - biosynthesis; Adenosine Triphosphate - metabolism; Animals; Calcium - metabolism; Cells, Cultured; Colon - cytology; Enteroendocrine Cells - drug effects; Enteroendocrine Cells - metabolism; Glucagon-Like Peptide 1 - metabolism; Incretins - metabolism; Indoles - pharmacology; Ions; Mice; NADP - metabolism; Potassium Channels, Voltage-Gated - metabolism; Potassium Chloride - pharmacology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.10.032

It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K+ channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca2+ entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolism. [Display omitted] •Bacterial metabolite indole modulates secretion of incretin peptide GLP-1•Indole widens the width of action potentials fired by L cells and elevates GLP-1•Prolonged exposure to indole inhibits ATP production and thus GLP-1 secretion Indole is the main metabolite produced by gut bacteria from tryptophan. Chimerel et al. demonstrate that indole modulates the hormone secretion of enteroendocrine L cells and reveal the molecular mechanism behind this modulation. These findings suggest that the production of indole by bacteria could have a major impact on host metabolism.