Dissecting effects of community context on a gut pathobiont in a model of childhood undernutrition. Host-pathobiont-microbiota interactions in undernutrition

To model how interactions between enteropathogens and gut microbial community members contribute to undernutrition, we colonized gnotobiotic mice fed representative Bangladeshi diets with sequenced bacterial strains cultured from fecal microbiota of 24-month-old Bangladeshis: one healthy, the other severely stunted/underweight. The undernourished donor’s collection contained an enterotoxigenic Bacteroides fragilis strain (ETBF), while the healthy donor’s collection contained two nontoxigenic strains (NTBF). Analyses of mice harboring either the unmanipulated culture collections or systematically manipulated versions revealed that ETBF was causally related to weight loss in the context of its native community, but not when introduced into the healthy donor’s community. This phenotype was transmissible from mothers to offspring and associated with derangements in host energy metabolism manifest by impaired TCA cycle activity and decreased acyl-CoA utilization. NTBF reduced ETBF expression of its enterotoxin and mitigated its effects on other healthy donor community members’ transcriptomes. These results illustrate how intraspecific (ETBF-NTBF) and interspecific interactions impact the effects of harboring this pathobiont.