SUMMARY 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.

Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.microbiome | barrier | IL-22

Cell 161, 264-276; April 9, 2015) 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.

There has been a striking generational increase in life-threatening food allergies in Westernized societies 1 , 2 One hypothesis to explain this rising prevalence is that 21 st century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early life alterations may be particularly detrimental. 3 , 4 To better understand how commensal bacteria regulate food allergy in humans we colonized germ free (GF) mice with feces from healthy or cow’s milk allergic (CMA) infants 5 . We show here that GF mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow’s milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transciptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a Clostridial species, Anaerostipes caccae , that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut.