A future food boom rescues the negative effects of early-life adversity on adult lifespan in a small mammal.

Early-life adversity, even when transient, can have lasting effects on individual phenotypes and reduce lifespan across species. If these effects can be mitigated by a high-quality later-life environment, then differences in future resources may explain variable resilience to early-life adversity. Using data from over 1000 wild North American red squirrels, we tested the hypothesis that the costs of early-life adversity for adult lifespan could be offset by later-life food abundance. We identified six adversities that reduced juvenile survival in the first year of life, though only one-birth date-had continued independent effects on adult lifespan. We then built a weighted early-life adversity (wELA) index integrating the sum of adversities and their effect sizes. Greater weighted early-life adversity predicted shorter adult lifespans in males and females, but a naturally occurring food boom in the second year of life ameliorated this effect. Experimental food supplementation did not replicate this pattern, despite increasing lifespan, indicating that the buffering effect of a future food boom may hinge on more than an increase in available calories. Our results suggest a non-deterministic role of early-life conditions for later-life phenotype, highlighting the importance of evaluating the consequences of early-life adversity in the context of an animal's entire life course.

Evolution of vertebral numbers in primates, with a focus on hominoids and the last common ancestor of hominins and panins.

The primate vertebral column has been extensively studied, with a particular focus on hominoid primates and the last common ancestor of humans and chimpanzees. The number of vertebrae in hominoids-up to and including the last common ancestor of humans and chimpanzees-is subject to considerable debate. However, few formal ancestral state reconstructions exist, and none include a broad sample of primates or account for the correlated evolution of the vertebral column. Here, we conduct an ancestral state reconstruction using a model of evolution that accounts for both homeotic (changes of one type of vertebra to another) and meristic (addition or loss of a vertebra) changes. Our results suggest that ancestral primates were characterized by 29 precaudal vertebrae, with the most common formula being seven cervical, 13 thoracic, six lumbar, and three sacral vertebrae. Extant hominoids evolved tail loss and a reduced lumbar column via sacralization (homeotic transition at the last lumbar vertebra). Our results also indicate that the ancestral hylobatid had seven cervical, 13 thoracic, five lumbar, and four sacral vertebrae, and the ancestral hominid had seven cervical, 13 thoracic, four lumbar, and five sacral vertebrae. The last common ancestor of humans and chimpanzees likely either retained this ancestral hominid formula or was characterized by an additional sacral vertebra, possibly acquired through a homeotic shift at the sacrococcygeal border. Our results support the 'short-back' model of hominin vertebral evolution, which postulates that hominins evolved from an ancestor with an African ape-like numerical composition of the vertebral column.

The glucocorticoid response to environmental change is not specific to agents of natural selection in wild red squirrels.

Evolutionary endocrinology aims to understand how natural selection shapes endocrine systems and the degree to which endocrine systems themselves can induce phenotypic responses to environmental changes. Such responses may be specialized in that they reflect past selection for responsiveness only to those ecological factors that ultimately influence natural selection. Alternatively, endocrine responses may be broad and generalized, allowing organisms to cope with a variety of environmental changes simultaneously. Here, we empirically tested whether the endocrine response of female North American red squirrels (Tamiasciurus hudsonicus) was specialized or generalized. We first quantified the direction and magnitude of natural selection acting on three female life history traits (parturition date, litter size, offspring postnatal growth rate) during 32 years of fluctuations in four potential ecological agents of selection (food availability, conspecific density, predator abundance, and temperature). Only three of the four variables (food, density, and predators) affected patterns of natural selection on female life history traits. We then quantified fecal glucocorticoid metabolites (FGMs) across 7 years and found that all four environmental variables, regardless of their effects on patterns of selection, were associated with glucocorticoid production. Our results provide support for a generalized, rather than specific, glucocorticoid response to environmental change that can integrate across multiple co-occurring environmental stressors.

Social correlates of androgen levels and dispersal age in juvenile male geladas.

Androgens offer a window into the timing of important male life history events such as maturation. However, when males are the dispersing sex, piecing together normative androgen profiles across development is challenging because dispersing males are difficult to track. Here, we examined the conditions that may be associated with male androgen status (via fecal androgen metabolites, fAMs) and age at dispersal in wild male geladas (Theropithecus gelada). Gelada male life histories are highly variable - dispersal may occur before sexual maturation, dispersal itself can be immediate or drawn out, and, due to their multi-leveled society, social conditions affecting dispersal can vary for juveniles living in different reproductive units within the same band. Using longitudinal data from known natal males, we examined how androgen levels and age at dispersal were associated with: (1) access to maternal resources (i.e., maternal rank, birth of a younger sibling, experiencing maternal loss), and (2) access to male peers (i.e., number of similar-aged males in their unit). We found that androgens were significantly lower in males with high-ranking mothers (in males >2.5 years of age; infant androgens were unrelated) and that having more male peers in their social group and larger groups overall predicted an earlier age at dispersal. Moreover, dispersal in geladas was not preceded or followed by a surge in androgen levels. Taken together, results suggest that social environments can cause individual variation in androgens and dispersal age. Whether this variation leads to differences in male fitness in later life remains to be determined.

Developmental responses to early-life adversity: Evolutionary and mechanistic perspectives.

Adverse ecological and social conditions during early life are known to influence development, with rippling effects that may explain variation in adult health and fitness. The adaptive function of such developmental plasticity, however, remains relatively untested in long-lived animals, resulting in much debate over which evolutionary models are most applicable. Furthermore, despite the promise of clinical interventions that might alleviate the health consequences of early-life adversity, research on the proximate mechanisms governing phenotypic responses to adversity have been largely limited to studies on glucocorticoids. Here, we synthesize the current state of research on developmental plasticity, discussing both ultimate and proximate mechanisms. First, we evaluate the utility of adaptive models proposed to explain developmental responses to early-life adversity, particularly for long-lived mammals such as humans. In doing so, we highlight how parent-offspring conflict complicates our understanding of whether mothers or offspring benefit from these responses. Second, we discuss the role of glucocorticoids and a second physiological system-the gut microbiome-that has emerged as an additional, clinically relevant mechanism by which early-life adversity can influence development. Finally, we suggest ways in which nonhuman primates can serve as models to study the effects of early-life adversity, both from evolutionary and clinical perspectives.

Steroid hormone concentrations in milk predict sex-specific offspring growth in a nonhuman primate.

OBJECTIVES: In humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. Here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone-sulfate (DHEAS) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates. METHODS: Demographic information, morphometrics, and milk samples were collected from rhesus macaque mothers and their infants at the California National Primate Research Center in Davis, California. Using linear models, we examined the relationship between maternal traits and milk hormone concentrations (N = 104 females) and explored the effect of milk hormones on the rate of offspring growth (N = 72 mother-infant dyads), controlling for available milk energy. RESULTS: Contrary to previous studies, we found that milk cortisol concentrations were categorically higher in multiparous females than in primiparous females. However, milk DHEAS concentrations decreased with maternal parity. Neither milk cortisol nor DHEAS were related to maternal rank. Finally, changes in milk hormones predicted offspring growth in a sex-specific and temporal manner: increases in cortisol from peak to late lactation predicted faster female growth, and increases in DHEAS concentrations from early to peak and peak to late lactation predicted faster male growth. CONCLUSIONS: Our findings shed light on how hormonal components of milk have sex-specific effects on offspring growth during early postnatal life with varying temporal windows of sensitivity.

Natural variation in fetal cortisol exposure is associated with neonatal body mass in captive vervet monkeys (Chlorocebus aethiops).

Poor maternal condition during gestation is commonly associated with impaired fetal growth in humans and other animals. Although elevated maternal glucocorticoids (GCs) are often implicated as the mechanism of intrauterine growth stunting, the direct contribution of maternal GCs remains unclear because enzymatic conversion of GCs at the placenta may limit the ability of maternal hormones to reach the fetus. Further, because previous studies on gestational stress have often employed synthetic GCs, which cross the placenta unobstructed, it remains unknown whether naturalistic endogenous GC elevations will have similar effects. Here, we use an unmanipulated colony of captive vervet monkeys (N = 18 mother-offspring dyads) to examine how maternal condition predicts maternal gestational hormones, and how these in turn predict neonatal body mass, especially in comparison with total prenatal hormone exposure as measured from neonatal hair. We focused on GCs and dehydroepiandrosterone-sulfate (DHEAS), an additional steroid suspected to influence growth. We found that measures of poor maternal condition (low body mass and low parity) were not associated with elevations in maternal GCs or DHEAS. Furthermore, only fetal GC exposure predicted neonatal body mass, while neither maternal GCs, nor maternal or fetal DHEAS, had any effect. Surprisingly, neonates exposed to higher gestational GCs were larger, rather than smaller at birth. Taken together, these results suggest that GC concentrations within a more naturalistic range may be positively rather than negatively associated with neonatal body mass. Further, the effect of maternal gestational GCs on neonatal mass may be modulated by placental control of GC exposure.

Composition and stability of the vervet monkey milk microbiome.

The human milk microbiome is vertically transmitted to offspring during the postnatal period and has emerged as a critical driver of infant immune and metabolic development. Despite this importance in humans, the milk microbiome of nonhuman primates remains largely unexplored. This dearth of comparative work precludes our ability to understand how species-specific differences in the milk microbiome may differentially drive maternal effects and limits how translational models can be used to understand the role of vertically transmitted milk microbes in human development. Here, we present the first culture-independent data on the milk microbiome of a nonhuman primate. We collected milk and matched fecal microbiome samples at early and late lactation from a cohort of captive lactating vervet monkeys (N = 15). We found that, similar to humans, the vervet monkey milk microbiome comprises a shared community of taxa that are universally present across individuals. However, unlike in humans, this shared community is dominated by the genera Lactobacillus, Bacteroides, and Prevotella. We also found that, in contrast to previous culture-dependent studies in humans, the vervet milk microbiome exhibits greater alpha-diversity than the gut microbiome across lactation. Finally, we did not find support for the translocation of microbes from the gut to the mammary gland within females (i.e., "entero-mammary pathway"). Taken together, our results show that the vervet monkey milk microbiome is taxonomically diverse, distinct from the gut microbiome, and largely stable. These findings demonstrate that the milk microbiome is a unique substrate that may selectively favor the establishment and persistence of particular microbes across lactation and highlights the need for future experimental studies on the origin of microbes in milk.

Vigilance for threat accounts for inter-individual variation in physiological responses to adversity in rhesus macaques: A cognition × environment approach.

Early life adversity (ELA) can lead to poor health later in life. However, there is significant variation in outcomes, with some individuals displaying resilience even in the face of adversity. Using longitudinal data collected from free-ranging rhesus macaques between birth and 3 years, we examined whether individual variation in vigilance for threat, an early emerging attentional bias, can account for variation in long-term outcomes between individuals reared in similar environments. We found that ELA and vigilance during infancy interact to predict physiological dysregulation in Sympathetic Nervous System (SNS) and Hypothalamic-Pituitary-Adrenal (HPA) stress responses during juvenility. During high stress periods, High ELA juveniles with high vigilance exhibit less asymmetry than High ELA juveniles with low vigilance. This suggests that although increased vigilance is viewed as a negative consequence of ELA, it might also be a mechanism by which vulnerable individuals proactively buffer themselves from negative outcomes in unstable or threatening environments.

Effects of early life adversity on cortisol/salivary alpha-amylase symmetry in free-ranging juvenile rhesus macaques.

Early life adversity (ELA) affects physiological and behavioral development. One key component is the relationship between the developing Hypothalamic-Pituitary-Adrenal (HPA) axis and the Sympathetic Nervous System (SNS). Recent studies suggest a relationship between early life adversity and asymmetry in cortisol (a measure of HPA activation) and salivary alpha-amylase (sAA: a correlate of SNS activation) responses to stress among human children, but to our knowledge there have been no comparable studies in nonhumans. Here, we investigate the responses of these two analytes in "low stress" and "high stress" situations in free-ranging juvenile rhesus macaques (Macaca mulatta) on Cayo Santiago, Puerto Rico. Behavioral data on maternal maltreatment were collected during the first 3months of life to determine individual rates of ELA, and saliva samples were collected from subjects noninvasively during juvenility. Irrespective of ELA, salivary alpha-amylase levels were lower in low stress situations and higher in high stress situations. For cortisol however, high ELA subjects exhibited higher low stress concentrations and blunted acute responses during high stress situations compared to moderate and low ELA subjects. Cortisol and sAA values were positively correlated among low ELA subjects, suggesting symmetry, but were uncorrelated or negatively correlated among moderate and high ELA subjects, suggesting asymmetry in these individuals. These findings indicate dysregulation of the stress response among juveniles maltreated during infancy: specifically, attenuated cortisol reactivity coupled with typical sAA reactivity characterize the stress response profiles of juveniles exposed to higher rates of ELA during the first 3months of life.

Consistent spatial patterns in microbial taxa of red squirrel gut microbiomes.

Gut microbiomes are diverse ecosystems whose drivers of variation remain largely unknown, especially in time and space. We analysed a dataset with over 900 red squirrel (Tamiasciurus hudsonicus) gut microbiome samples to identify the drivers of gut microbiome composition in this territorial rodent. The large-scale spatiotemporal replication in the data analysed was an essential component of understanding the assembly of these microbial communities. We identified that the spatial location of the sampled squirrels in their local environment is a key contributor to gut microbial community composition. The non-core gut microbiome (present in less than 75% of gut microbiome samples) had highly localised spatial patterns throughout different seasons and different study areas in the host squirrel population. The core gut microbiome, on the other hand, showed some spatial patterns, though fewer than in the non-core gut microbiome. Environmental transmission of microbiota is the likely contributor to the spatiotemporal distribution observed in the North American red squirrel gut microbiome.

Phenotype-environment mismatch errors enhance lifetime fitness in wild red squirrels.

Mismatches between an organism's phenotype and its environment can result in short-term fitness costs. Here, we show that some phenotype-environment mismatch errors can be explained by asymmetrical costs of different types of errors in wild red squirrels. Mothers that mistakenly increased reproductive effort when signals of an upcoming food pulse were absent were more likely to correctly increase effort when a food pulse did occur. However, mothers that failed to increase effort when cues of an upcoming food pulse were present suffered lifetime fitness costs that could only be offset through food supplementation. In fluctuating environments, such phenotype-environment mismatches may therefore reflect a bias to overestimate environmental cues and avoid making the costliest error, ultimately enhancing lifetime fitness.

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.

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.

Glucocorticoids coordinate changes in gut microbiome composition in wild North American red squirrels.

The gut microbiome impacts host health and fitness, in part through the diversification of gut metabolic function and pathogen protection. Elevations in glucocorticoids (GCs) appear to reduce gut microbiome diversity in experimental studies, suggesting that a loss of microbial diversity may be a negative consequence of increased GCs. However, given that ecological factors like food availability and population density may independently influence both GCs and microbial diversity, understanding how these factors structure the GC-microbiome relationship is crucial to interpreting its significance in wild populations. Here, we used an ecological framework to investigate the relationship between GCs and gut microbiome diversity in wild North American red squirrels (Tamiasciurus hudsonicus). As expected, higher GCs predicted lower gut microbiome diversity and an increase in metabolic taxa. Surprisingly, but in line with prior empirical studies on wild animals, gastrointestinal pathogens decreased as GCs increased. Both dietary heterogeneity and an upcoming food pulse exhibited direct effects on gut microbiome diversity, whereas conspecific density and reproductive activity impacted diversity indirectly via changes in host GCs. Our results provide evidence of a gut-brain axis in wild red squirrels and highlight the importance of situating the GC-gut microbiome relationship within an ecological framework.

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.

Increased variation in numbers of presacral vertebrae in suspensory mammals.

Restricted variation in numbers of presacral vertebrae in mammals is a classic example of evolutionary stasis. Cervical number is nearly invariable in most mammals, and numbers of thoracolumbar vertebrae are also highly conserved. A recent hypothesis posits that stasis in mammalian presacral count is due to stabilizing selection against the production of incomplete homeotic transformations at the lumbo-sacral border in fast-running mammals, while slower, ambulatory mammals more readily tolerate intermediate lumbar/sacral vertebrae. We test hypotheses of variation in presacral numbers of vertebrae based on running speed, positional behaviour and vertebral contribution to locomotion. We find support for the hypothesis that selection against changes in presacral vertebral number led to stasis in mammals that rely on dorsomobility of the spine during running and leaping, but our results are independent of running speed per se. Instead, we find that mammals adapted to dorsostability of the spine, such as those that engage in suspensory behaviour, demonstrate elevated variation in numbers of presacral vertebrae compared to dorsomobile mammals. We suggest that the evolution of dorsostability and reduced reliance on flexion and extension of the spine allowed for increased variation in numbers of presacral vertebrae, leading to departures from an otherwise stable evolutionary pattern.