Intergenerational transmission in mice of small intestinal microbiota from stunted children contributes to growth defects and enteropathy
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 signaling pathways related to intestinal epithelial cell renewal, barrier integrity and immune function. Screening of cohoused mice harbouring the inflammatory or non-inflammatory consortia identified Campylobacter concisus as an inducer of pro-inflammatory cytokine signaling in a host nitric oxide synthase-dependent manner. This preclinical model could facilitate small intestinal microbiota-targeted therapeutics for intergenerational undernutrition.