Editors' ChoiceHost-Microbe Interactions

Microbes message gut secretory cells

Sci. Signal.  21 Apr 2015:
Vol. 8, Issue 373, pp. ec101
DOI: 10.1126/scisignal.aab3722

The microbes that live in our guts are important for promoting health. Germ-free mice have reduced gastrointestinal (GI) motility and reduced amounts of the hormone and neurotransmitter serotonin, which promotes GI motility and is important for platelet activation and aggregation (see Ridaura and Belkaid). Yano et al. found that the colons of germ-free mice had less expression of TPH1 (encoding the rate-limiting enzyme in serotonin synthesis in the periphery), decreased amount of serotonin in enterochromaffin cells, and increased amount of the transcript for the serotonin uptake transporter SLC6A4. Germ-free mice also had increased amounts of the serotonin precursor tryptophan in feces and circulation. Supplementing the diet of the germ-free mice with the product of Tph increased serotonin in the colon and circulation, as did reconstituting the gut flora with spore-forming microbes (SPF mice). Compared with germ-free mice, SPF mice had increased expression of TPH1, reduced expression of SLC6A4, and increased amount of serotonin in the enterochromaffin cells, effects that were blocked by intrarectal administration of an inhibitor of Tph activity. Compared with germ-free mice, SPF mice exhibited increased GI motility (indicated by reduced transit time and increased fecal output), increased activity of the serotonin receptor 5HT4 in the colon (indicated by increased expression of a 5HT4-responsive gene), and increased platelet activation and aggregation. Metabolomic profiling identified α-tocopheral, several short chain fatty acids, doxycholate, p-aminobenzoate, and tyramine as candidates responsible for the differences in the SPF and germ-free mice. Addition of any of these molecules to the medium stimulated TPH1 expression and the amount of serotonin in an enterochromaffin cell line and, when introduced into the colon, also increased serotonin abundance in the colon and serum in mice. Thus, spore-forming microbes produce metabolites that stimulate serotonin production by enterochromaffin cells that contribute to the peripheral effects of this hormone and neurotransmitter.

J. M. Yano, K. Yu, G. P. Donaldson, G. G. Shastri, P. Ann, L. Ma, C. R. Nagler, R. F. Ismagilov, S. K. Mazmanian, E. Y. Hsiao, Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276 (2015). [PubMed]

V. Ridaura, Y. Belkaid, Gut microbiota: The link to your second brain. Cell 161, 193–194 (2015). [PubMed]