Enteropathy produced in mice by intergenerational transmission of small intestinal microbiota from undernourished children

Environmental enteric dysfunction (EED), a small intestinal disorder prevalent in undernourished children with stunted growth and their undernourished mothers, is associated with gut mucosal barrier disruption and decreased absorptive capacity. Here we provide preclinical evidence that intergenerational transmission of a perturbed small intestinal microbiota contributes to pathogenesis. One of two bacterial consortia cultured from duodenal aspirates obtained from Bangladeshi children with EED induced local and systemic inflammation in female gnotobiotic mice, resulting in impaired prenatal and postnatal growth in their offspring. Immunologic changes in pups phenocopied features of EED in children, and dam-to-pup transmission of this consortium altered signalling pathways related to intestinal epithelial cell renewal, barrier integrity and immune function. Screening of co-housed mice harbouring the inflammatory or non-inflammatory consortia identified Campylobacter concisus as an inducer of pro-inflammatory cytokine signalling in a host nitric oxide synthase-dependent manner. This preclinical model could facilitate small intestinal microbiota-targeted therapeutics for intergenerational undernutrition.