Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis
Abstract
The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.
Additional Information
© 2015 Elsevier Inc. Received: September 25, 2014; Revised: December 16, 2014; Accepted: February 18, 2015; Published: April 9, 2015. The authors acknowledge the assistance of Andrew Stefka and Taylor Feehley (University of Chicago) for contributing pilot serum and fecal samples, Taren Thron, Sara McBride, and Alyssa Maskell for caring for the animals, Drs. Nathan Dalleska and Jesse Allen (Caltech) for conducting pilot LC/MS experiments, Said Bogatyrev (Caltech) for helpful advice, Natasha Shelby (Caltech) for editing the manuscript, and the late Dr. Paul H. Patterson for his valuable support. This work was supported by the NIH Director's Early Independence Award (5DP5OD017924 to E.Y.H.), Caltech Center for Environmental Microbial Interactions Award (to E.Y.H.), National Science Foundatio (NSF) Emerging Frontiers in Research and Innovation Award (EFRI-1137089 to R.F.I. and S.K.M.), National Human Genome Research Institute (NHGRI) grant (R01HG005826 to R.F.I.), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant (DK078938 to S.K.M.) and National Institute of Mental Health (NIMH) grant (MH100556 to S.K.M.), National Institute of Allergy and Infectious Diseases (NIAID) grant (AI106302 to C.R.N.), and Food Allergy Research and Education (FARE) and University of Chicago Digestive Diseases Center Core Grant (P30DK42086 to C.R.N.).Errata
In Figure S5D of this article, the representative flow cytometry plot of forward versus side scatter for unstimulated platelets was incorrectly duplicated during the final formatting of the paper for SPF+PCPA and GF conditions. The figure has been corrected online, and the originally published descriptions of the results in the text and figure legend are accurate. In Figure 3A, the "GF+conv" bar represents germ-free (GF) mice conventionalized with standard pathogen-free (SPF) microbiota on postnatal day 21 (P21). The published main text incorrectly referred to conventionalization on P42. Though we show in Figure 1B very similar levels of colonic serotonin after conventionalization on P21 versus P42, the "GF+conv" data in Figure 3A is specifically from GF mice conventionalized on P21. This error in the text has also been corrected online. Overall, these changes have no bearing on the experimental results or conclusions presented in the manuscript. We apologize for any inconvenience that these errors have caused.Attached Files
Accepted Version - nihms669675.pdf
Supplemental Material - table_s1.xls
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Additional details
- PMCID
- PMC4393509
- Eprint ID
- 56514
- Resolver ID
- CaltechAUTHORS:20150409-093248232
- 5DP5OD017924
- NIH
- Caltech Center for Environmental Microbial Interactions (CEMI)
- EFRI-1137089
- NSF
- R01HG005826
- NIH
- DK078938
- NIH
- MH100556
- NIH
- AI106302
- NIH
- P30DK42086
- NIH
- Created
-
2015-04-09Created from EPrint's datestamp field
- Updated
-
2023-06-01Created from EPrint's last_modified field
- Caltech groups
- Caltech Center for Environmental Microbial Interactions (CEMI)