Microbiota-dependent early life programming of gastrointestinal motility

Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later – or not at all – showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility. Overall design: Microbe-lacking (“germ-free”, GF) mice, were given fecal microbiota transplantation (FMT) at weaning (4wC) or as adults (12wC). Gene expression was evaluated from RNAseq of colonic muscularis propria of adult 4wC and 12wC mice at least 4 weeks after FMT and of adult GF and conventional (SPF) mice.