Maturation of the infant rhesus macaque gut microbiome and its role in the development of diarrheal disease

Abstract

Background Diarrhea is the second leading cause of death in children under 5 years of age. 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 this association remains incomplete. Infant rhesus macaques ( Macaca mulatta ) are susceptible to diarrhea making them an ideal model to address this question. Results 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. Moreover, the microbiome of the captive reared infant rhesus macaque more closely resembles that of human infants in the developing world than in the western world. Importantly, prior to disease onset, the gut microbiome of infants that later develop diarrhea is enriched in pathways of immunomodulatory metabolite synthesis, while those of infants that remain asymptomatic are enriched in pathways for short-chain fatty acid production. We identify Prevotella strains that are more abundant at 1 month in infants that later develop diarrhea. At 8 months, the microbiomes of animals that experience diarrhea show increased abundance of Campylobacter and a reduction in Helicobacter macacae . 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 potential markers of susceptibility to diarrhea that could be modulated to improve infant health, especially in the developing world. Electronic supplementary material The online version of this article (10.1186/s13059-019-1789-x) contains supplementary material, which is available to authorized users.

Dynamic age-associated changes and their driver microbes in healthy gut microbiota of captive crab-eating macaques

“…We also notice that Bifidobacterium, the key probiotics for the metabolism of oligosaccharides in breast milk [43], reduced with age. The abundance of Bifidobacterium was lower in our post-weaning infant macaques than that in lactating macaques reported by Rhoades et al [9].…”

“…Helicobacter macacae from the genus have been reported to be frequently detected in rhesus monkeys without a diarrheal history [47]. Rhoades et al report that 8-month infant remained asymptomatic for diarrhea were enriched for the species [9]. It should be taken into account that all macaques in the current study were in good health.…”

“…The development of human gut microbiota, with dynamic changes after birth, have been implicated to play an active role concomitantly with the host's development and aging [7]. After first colonization at birth, the postnatal gut microbiota develops rapidly in the first few months of life [8,9]. By 1 week of age, the infant gut microbiota has already become very similar to that at one-month old [10].…”

Modeling of viral-bacterial infections against antibiotic-induced intestinal dysbiosis

“…According to WHO, about 1.7 billion cases of acute diarrhea are reported annually alone in children [1]. Among microorganisms of bacterial nature, the main agents of AII are representatives of the family Enterobacteriaceae [14,15]. Viruses are also important etiologic factors of AII in children, especially in early childhood.…”

Expanding the scope and scale of microbiome research

“…Moving beyond a parochial view of our own species, Rhoades et al [13] provide the highest-resolution view yet of the development of the microbiome of infant Rhesus macaques, an important model animal for biomedical research, whereas Malmuthuge et al [14] provide a high-resolution view of the developing rumen microbiome.…”