Regulation of serotonin production by specific microbes from piglet gut

Background Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut.Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models.However,how gut microbes regulate intestinal serotonin production in piglets remains vague.To investigate the relationship between microbiota and serotonin specifically in the colon,microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion.Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investi-gate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells.Results Antibiotic infusion increased quantities of Lactobacillus amylovorus(LA)that positively correlated with increased serotonin concentrations in the colon,while no effects observed for Limosilactobacillus reuteri(LR).To understand how microbes regulate serotonin,representative strains of LA,LR,and Streptococcus alactolyticus(SA,enriched in feces from prior observation)were selected for cell culture studies.Compared to the control group,LA,LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1(TPH1)expression and promoted serotonin production in IPEC-J2 cells,while in RIN-14B cells only LA exerted similar action.To investigate potential mechanisms mediated by microbe-derived molecules,microbial metabolites including lactate,acetate,glutamine,andγ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacte-rial supernatant.Among these metabolites,acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1.Similar effects were also recapitulated when treating the cells with AR420626,an agonist targeting free fatty acid receptor 3.Conclusions Overall,these results suggest that Lactobacillus amylovorus showed a positive correlation with sero-tonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures.These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host,which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.