Maternal effects on early-life gut microbiota maturation in a wild nonhuman primate.

Early-life microbial colonization is an important process shaping host physiology,1-3 immunity,4-6 and long-term health outcomes7-10 in humans. However, our understanding of this dynamic process remains poorly investigated in wild animals,11-13 where developmental mechanisms can be better understood within ecological and evolutionarily relevant contexts.11,12 Using one of the largest developmental datasets on a wild primate-the gelada (Theropithecus gelada)-we used 16S rRNA amplicon sequencing to characterize gut microbiota maturation during the first 3 years of life and assessed the role of maternal effects in shaping offspring microbiota assembly. In contrast to recent data on chimpanzees, postnatal microbial colonization in geladas was highly similar to humans:14 microbial alpha diversity increased rapidly following birth, followed by gradual changes in composition until weaning. Dietary changes associated with weaning (from milk- to plant-based diet) were the main drivers of shifts in taxonomic composition and microbial predicted functional pathways. Maternal effects were also an important factor influencing the offspring gut microbiota. During nursing (<12 months), offspring of experienced (multi-time) mothers exhibited faster functional microbial maturation, likely reflecting the general faster developmental pace of infants born to these mothers. Following weaning (>18 months), the composition of the juvenile microbiota tended to be more similar to the maternal microbiota than to the microbiota of other adult females, highlighting that maternal effects may persist even after nursing cessation.15,16 Together, our findings highlight the dynamic nature of early-life gut colonization and the role of maternal effects in shaping this trajectory in a wild primate.

The early life microbiota mediates maternal effects on offspring growth in a nonhuman primate.

Maternal parity can impact offspring growth, but the mechanisms driving this effect are unclear. Here, we test the hypothesis that vertically transmitted microbiota may be one potential mechanism. We analyzed 118 fecal and milk samples from mother-offspring vervet monkey dyads across the first 6 months of life. Despite poorer milk production, offspring born to low parity females grew larger than their counterparts. These offspring exhibited reduced alpha diversity in the first days of life, stronger seeding of maternal milk microbiota, Bacteroides fragilis dominance, and a greater abundance of glycan utilization pathways. Moreover, the attainment of greater body mass by 6 months of age was mediated by reduced early life alpha diversity and B. fragilis dominance. This work demonstrates that the establishment of a specialized, milk-oriented gut microbiota promotes infant growth and suggests an evolutionarily conserved developmental role of B. fragilis in primates.

Seasonal shifts in the gut microbiome indicate plastic responses to diet in wild geladas.

BACKGROUND: Adaptive shifts in gut microbiome composition are one route by which animals adapt to seasonal changes in food availability and diet. However, outside of dietary shifts, other potential environmental drivers of gut microbial composition have rarely been investigated, particularly in organisms living in their natural environments. RESULTS: Here, we generated the largest wild nonhuman primate gut microbiome dataset to date to identify the environmental drivers of gut microbial diversity and function in 758 samples collected from wild Ethiopian geladas (Theropithecus gelada). Because geladas live in a cold, high-altitude environment and have a low-quality grass-based diet, they face extreme thermoregulatory and energetic constraints. We tested how proxies of food availability (rainfall) and thermoregulatory stress (temperature) predicted gut microbiome composition of geladas. The gelada gut microbiome composition covaried with rainfall and temperature in a pattern that suggests distinct responses to dietary and thermoregulatory challenges. Microbial changes were driven by differences in the main components of the diet across seasons: in rainier periods, the gut was dominated by cellulolytic/fermentative bacteria that specialized in digesting grass, while during dry periods the gut was dominated by bacteria that break down starches found in underground plant parts. Temperature had a comparatively smaller, but detectable, effect on the gut microbiome. During cold and dry periods, bacterial genes involved in energy, amino acid, and lipid metabolism increased, suggesting a stimulation of fermentation activity in the gut when thermoregulatory and nutritional stress co-occurred, and potentially helping geladas to maintain energy balance during challenging periods. CONCLUSION: Together, these results shed light on the extent to which gut microbiota plasticity provides dietary and metabolic flexibility to the host, and might be a key factor to thriving in changing environments. On a longer evolutionary timescale, such metabolic flexibility provided by the gut microbiome may have also allowed members of Theropithecus to adopt a specialized diet, and colonize new high-altitude grassland habitats in East Africa. Video abstract.

Rhesus macaques as a tractable physiological model of human ageing.

Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from short-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research owing to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with the model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population. This article is part of the theme issue 'Evolution of the primate ageing process'.