MICROBIOTA DYSBIOSIS INDUCED BY DEFECT OF ENTERIC ANTIMICROBIAL ACTIVITY TRIGGERS VISCERAL HYPERSENSITIVITY IN YOUNG ADULT MICE

Paneth cell-derived antimicrobial peptides like lysozyme provide antibacterial protection and maintain intestinal homeostasis. In this study, we analyzed the consequences of altered Paneth cells function on fecal antimicrobial activity, intestinal homeostasis and visceral sensitivity at adulthood. In 50-days old Sox9flox/flox-vil-Cre female mice, absence of Paneth increased fecal population of Enterobacteriaceae associated to visceral hypersensitivity. Daily gavage of conventional adult mice with 109 commensal Escherichia coli, induced visceral hypersensitivity. Occurrence of adverse events during neonatal period is known to impair intestinal homeostasis establishment. Maternal separation (MS) is a well described rodent model of psychological stress characterized by a decrease of intestinal secretory cells and visceral hypersensitivity mimicking what we observed in Sox9flox/flox-vil-cre mice. We wondered if in this model we also observed a dysbiosis in favor of Enterobacteriaceae. Mice submitted to MS, presented a defect of fecal antimicrobial activity associated with a fecal overgrowth of Enterobacteriaceae. Furthermore, this antimicrobial defect and its consequences on visceral sensitivity were prevented by an oral administration of lysozyme. Altogether our results show that a defect of enteric antimicrobial functions leads to microbiota dysbiosis in favor of Enterobacteriaceae responsible for visceral hypersensitivity providing new mechanistic insights in maternal separation-induced visceral hypersensitivity