Diarrhea as a cause and consequence of reduced gut microbial diversity among undernourished children in Peru

Background. The detrimental effects of diarrhea on child growth and survival are well-documented but underlying mechanisms remain poorly understood. Recent evidence demonstrates that the gut microbiota may influence infection and growth in early life. We assessed associations between diarrhea and gut bacterial diversity among infants with high burden of undernutrition in the Peruvian Amazon. Methods. Diarrheal specimens and routine monthly fecal samples were collected from 271 children 0-24m of age. Specimens (n=928) obtained at quarter year intervals were selected to identify fecal microbiota composition and generate indices of bacterial diversity and richness (Shannon, Simpson, CHAO1, Phylogenetic Diversity). Longitudinal associations between diarrhea and microbiota configuration were investigated using multiple linear regression, adjusting for within-child correlations, age, breastfeeding, infection and antibiotic history, plus dietary diversity. Findings. Cumulative diarrheal frequency, duration and severity were associated with significant, sustained reductions in bacterial diversity and richness (p<0·05), and gut bacterial diversity at 6m was predictive of future diarrhea. Lower gut diversity was associated with increased incidence of subsequent diarrheal episodes, with a 1-unit increase in the Shannon Index at 6m corresponding with a mean reduction of 1·3 diarrheal episodes from 6-24m of age. In addition, the abundances of several specific bacteria were predictive of subsequent diarrheal episodes. Compared to children who were not born stunted, children who were stunted at birth experienced greater perturbations in their gut microbiota per diarrheal episode and exhibited significant differences in the representation of several bacterial taxa.Interpretation. Disruptions to the development of a healthy gut microbiota are one effect of repeated cycles of diarrheal disease, with stunted children exhibiting significantly greater impairments in community resiliency after diarrheal episodes, which in turn may further contribute to their growth faltering.