(B) Platelet activation, as measured by percentage of large, high granularity (FSC high, SSC high) events after collagen stimulation relative to unstimulated controls. (A) Time to cessation of bleeding in response to tail injury. SPF=specific pathogen-free (conventionally-colonized), GF=germ-free, Sp=spore-forming bacteria, PCPA=para-chlorophenylalanine. Data are normalized to expression levels in SPF mice. (D) Colonic expression of TPH1 relative to GAPDH.
(C) Levels of colon 5-HT relative to total protein after intrarectal treatment with the Tph inhibitor, PCPA, or vehicle. Data are normalized to colon 5-HT relative to total protein in SPF mice. (B) Levels of colon 5-HT relative to total protein. uniformis P21 colonization, n=4 Bd= Bacteroides consortium, n=3. fragilis monoassociation (BF), n=6 SFB=Segmented Filamentous Bacteria monoassociation, n=4 ASF=Altered Schaedler Flora P21 colonization, n=4 Sp=spore-forming bacteria, P21 colonization, n=4 B.
SPF, n=13 GF, n=17 GF+conv.=P21 conventionalization, n=4 SPF+Abx= P42 antibiotic treatment, n=7 B. Data are normalized to serum 5-HT levels in SPF 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.Ĭopyright © 2015 Elsevier Inc. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. 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. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. 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. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. 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.