Maturation of the infant rhesus macaque (Macaca mulatta) gut microbiome and its role in the development of diarrheal disease

ABSTRACTBackground: Diarrhea is the second leading cause of death in children under five years of age, resulting in nutrient malabsorption and growth stunting. Enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. Although the gut microbiota is believed to play a role in susceptibility to diarrheal diseases, our understanding of the mechanisms underlying this association remains incomplete. Infant rhesus macaques (Macaca mulatta) are naturally susceptible to diarrhea making them an ideal model to address this question.Results: The microbiome of the captive reared infant rhesus macaque more closely resembles that of human children in the developing world than western. The maturation of the infant rhesus macaque gut microbiome throughout the first 8 months of life occurs in a similar pattern as that described for human infants. Additionally, prior to disease onset, the gut microbiome of infants that later developed diarrhea was enriched in pathways of immunomodulatory metabolites synthesis, while those of infants that remained asymptomatic were enriched in pathways for short chain fatty acid production. Moreover, we identified Prevotella strains that are more abundant at the 1-month time-point in infants that later developed diarrhea. At the 8-month time point, the microbiomes of animals that experienced diarrhea showed increased abundance of Campyloabcter and a reduction in Helicobacter.Conclusion: The composition of the microbial community could provide a phenotypic marker of an infant's susceptibility to diarrheal disease. Given the significant physiological and immunological similarities between human and nonhuman primates, these findings provide insight into diarrheal susceptibility in humans and the effects of infection/treatment on the gut microbiome.