UC San Diego

The intestinal microbiome influences host gastrointestinal development, nutritional status, and mucosal immunity, and thus plays important functions in health and disease. However, under some conditions, constituents of the microbiota can become pathogenic to the host and cause disease. The factors that maintain the mutualistic relationship between the host and microbiota and those that drive microbial virulence remain incompletely understood. Escherichia coli are one of the pioneer organisms to colonize the intestine of a newborn shortly after birth and remain as lifelong colonizers of the healthy microbiome. However, numerous stunted infant cohort studies have reported an intestinal expansion of Enterobacteriaceae members, including E. coli during state of undernutrition. To elucidate the roles of E. coli strains on postnatal development, we performed a candidate screen using different strains of E. coli to observe the effect of the colonization of individual E. coli strain on growth. We identified an E. coli strain that behaves as a commensal when colonizing the adult murine intestine, but when colonizing the neonatal intestine, it displays pathogenic behavior by impairing the host’s development. The E. coli-induced growth retardation results in impaired downstream signaling of insulin-like growth factor 1 (IGF-1) and reduced adipose and lean muscle mass, indicating a state of malnourishment in the neonates. We found that colonization of this particular E. coli strain causes growth stunting by manipulating important maternal behaviors that are instrumental for neonatal nurturing and feeding. Our discovery offers a novel gnotobiotic mouse model of failure-to-thrive (FTT), that integrates microbial manipulation of host behavior and metabolic phenotypes.