Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.

Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat C. difficile infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. Prior work indicates that FMT is safe in marmosets and may successfully mediate gut microbiome function and host health. This narrative review (1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, (2) summarizes the prior use of FMT in marmosets, (3) outlines a protocol synthesized from prior literature for studying FMT in aging marmosets, and (4) describes limitations, knowledge gaps, and future research needs in this field.

The potential importance of the built-environment microbiome and its impact on human health.

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.

Effects of leaf herbivory and autumn seasonality on plant secondary metabolites: A meta-analysis.

Plant secondary metabolites (PSMs) are produced by plants to overcome environmental challenges, both biotic and abiotic. We were interested in characterizing how autumn seasonality in temperate and subtropical climates affects overall PSM production in comparison to herbivory. Herbivory is commonly measured between spring to summer when plants have high resource availability and prioritize growth and reproduction. However, autumn seasonality also challenges plants as they cope with limited resources and prepare survival for winter. This suggests a potential gap in our understanding of how herbivory affects PSM production in autumn compared to spring/summer. Using meta-analysis, we recorded overall production of 22 different PSM subgroups from 58 published papers to calculate effect sizes from herbivory studies (absence to presence) and temperate to subtropical seasonal studies (summer to autumn), while considering other variables (e.g., plant type, increase in time since herbivory, temperature, and precipitation). We also compared production of five phenolic PSM subgroups - hydroxybenzoic acids, flavan-3-ols, flavonols, hydrolysable tannins, and condensed tannins. We wanted to detect a shared response across all PSMs and found that herbivory increased overall PSM production in herbaceous plants. Herbivory was also found to have a positive effect on individual PSM subgroups, such as flavonol production, while autumn seasonality was found to have a positive effect on flavan-3-ol and condensed tannin production. We discuss how these responses might stem from plants producing some PSMs constitutively, whereas others are induced only after herbivory, and how plants produce metabolites with higher costs only during seasons when other resources for growth and reproduction are less available, while other phenolic PSM subgroups serve more than one function for plants and such functions can be season dependent. The outcome of our meta-analysis is that autumn seasonality changes some PSM production differently from herbivory, and we see value in further investigating seasonality-herbivory interactions with plant chemical defense.

Host-gut microbiota interactions during pregnancy.

Mammalian pregnancy is characterized by a well-known suite of physiological changes that support fetal growth and development, thereby positively affecting both maternal and offspring fitness. However, mothers also experience trade-offs between current and future maternal reproductive success, and maternal responses to these trade-offs can result in mother-offspring fitness conflicts. Knowledge of the mechanisms through which these trade-offs operate, as well as the contexts in which they operate, is critical for understanding the evolution of reproduction. Historically, hormonal changes during pregnancy have been thought to play a pivotal role in these conflicts since they directly and indirectly influence maternal metabolism, immunity, fetal growth and other aspects of offspring development. However, recent research suggests that gut microbiota may also play an important role. Here, we create a foundation for exploring this role by constructing a mechanistic model linking changes in maternal hormones, immunity and metabolism during pregnancy to changes in the gut microbiota. We posit that marked changes in hormones alter maternal gut microbiome composition and function both directly and indirectly via impacts on the immune system. The gut microbiota then feeds back to influence maternal immunity and metabolism. We posit that these dynamics are likely to be involved in mediating maternal and offspring fitness as well as trade-offs in different aspects of maternal and offspring health and fitness during pregnancy. We also predict that the interactions we describe are likely to vary across populations in response to maternal environments. Moving forward, empirical studies that combine microbial functional data and maternal physiological data with health and fitness outcomes for both mothers and infants will allow us to test the evolutionary and fitness implications of the gestational microbiota, enriching our understanding of the ecology and evolution of reproductive physiology.

Time to rethink academic publishing: the peer reviewer crisis.

There is concern that the time taken to publish academic papers in microbiological science has significantly increased in recent years. While the data do not specifically support this, evidence suggests that editors are having to invite more and more reviewers to identify those willing to perform peer review.

Interactions with alloparents are associated with the diversity of infant skin and fecal bacterial communities in Chicago, United States.

INTRODUCTION: Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin. METHODS: To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States. RESULTS: Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status. CONCLUSION: This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.

Human-influenced diets affect the gut microbiome of wild baboons.

Industrialized diets that incorporate processed foods and are often high in simple sugars and fats and low in fiber have myriad health impacts, many of which may operate via impacts on the gut microbiota. Examining how these diets affect the gut microbiota can be challenging given that lab animal models experience altered environmental contexts, and human studies include a suite of co-varying cultural and environmental factors that are likely to shape the gut microbiota alongside diet. To complement these approaches, we compare the microbiomes of wild populations of olive baboons (Papio anubis) with differential access to human trash high in processed foods, simple sugars, and fats in Rwanda's Akagera National Park. Baboons are a good model system since their microbiomes are compositionally similar to those of humans. Additionally, this population inhabits a common environment with different social groups consuming qualitatively different amounts of human trash, limiting variation in non-dietary factors. Using 16S rRNA gene amplicon sequencing we find that baboons with unlimited access to human trash have reduced microbial alpha diversity and reduced relative abundances of fiber-degrading taxa such as Ruminococcaceae, Prevotellaceae, and Lachnospiraceae. In contrast, baboons with limited access to human trash have a microbiome more similar to that of baboons with no access to human trash. Our results suggest that while a human-influenced diet high in processed foods, simple sugars, and fats is sufficient to alter the microbiome in wild baboons, there is a minimum threshold of dietary alteration that must occur before the microbiome is substantially altered. We recommend that data from wild primate populations such as these be used to complement ongoing research on diet-microbiome-health interactions in humans and lab animal models.

Antibiotic resistance and mecA characterization of Staphylococcus hominis from filarial lymphedema patients in the Ahanta West District, Ghana: A cross-sectional study.

Background and Aim: Filarial infections affect over 150 million people in the tropics. One of the major forms of filarial pathologies is lymphedema; a condition where the immune response is significantly altered, resulting in changes in the normal flora. Staphylococcus hominis, a human skin commensal, can also be pathogenic in immunocompromised individuals. Therefore, there is the possibility that S. hominis could assume a different behavior in filarial lymphedema patients. To this end, we investigated the levels of antibiotic resistance and extent of mecA gene carriage in S. hominis among individuals presenting with filarial lymphedema in rural Ghana. Method: We recruited 160 individuals with stages I-VII lymphedema, in a cross-sectional study in the Ahanta West District of the Western Region of Ghana. Swabs from lymphedematous limb ulcers, pus, and cutaneous surfaces were cultured using standard culture-based techniques. The culture isolates were subjected to Matrix-Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) mass spectrometry for bacterial identification. Antimicrobial susceptibility testing (AST) was performed using the Kirby-Bauer method. mecA genes were targeted by polymerase chain reaction for strains that were cefoxitin resistant. Results: In all, 112 S. hominis were isolated. The AST results showed resistance to chloramphenicol (87.5%), tetracycline (83.3%), penicillin (79.2%), and trimethoprim/sulphamethoxazole (45.8%). Of the 112 strains of S. hominis, 51 (45.5%) were resistant to cefoxitin, and 37 (72.5%) of the cefoxitin-resistant S. hominis haboured the mecA gene. Conclusion: This study indicates a heightened level of methicillin-resistant S. hominis isolated among filarial lymphedema patients. As a result, opportunistic infections of S. hominis among the already burdened filarial lymphedema patients in rural Ghana may have reduced treatment success with antibiotics.

Prenatal household size and composition are associated with infant fecal bacterial diversity in Cebu, Philippines.

OBJECTIVES: The gut microbiome (GM) connects physical and social environments to infant health. Since the infant GM affects immune system development, there is interest in understanding how infants acquire microbes from mothers and other household members. MATERIALS AND METHODS: As a part of the Cebu Longitudinal Health and Nutrition Survey (CLHNS), we paired fecal samples (proxy for the GM) collected from infants living in Metro Cebu, Philippines at 2 weeks (N = 39) and 6 months (N = 36) with maternal interviews about prenatal household composition. We hypothesized that relationships between prenatal household size and composition and infant GM bacterial diversity (as measured in fecal samples) would vary by infant age, as well as by household member age and sex. We also hypothesized that infant GM bacterial abundances would differ by prenatal household size and composition. RESULTS: Data from 16 S rRNA bacterial gene sequencing show that prenatal household size was the most precise estimator of infant GM bacterial diversity, and that the direction of the association between this variable and infant GM bacterial diversity changed between the two time points. The abundances of bacterial families in the infant GM varied by prenatal household variables. CONCLUSIONS: Results highlight the contributions of various household sources to the bacterial diversity of the infant GM, and suggest that prenatal household size is a useful measure for estimating infant GM bacterial diversity in this cohort. Future research should measure the effect of specific sources of household bacterial exposures, including social interactions with caregivers, on the infant GM.

Factors influencing terrestriality in primates of the Americas and Madagascar.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Limited microbiome differences in captive and semi-wild primate populations consuming similar diets.

Gut microbial communities are shaped by a myriad of extrinsic factors, including diet and the environment. Although distinct human populations consistently exhibit different gut microbiome compositions, variation in diet and environmental factors are almost always coupled, making it difficult to disentangle their relative contributions to shaping the gut microbiota. Data from discrete animal populations with similar diets can help reduce confounds. Here, we assessed the gut microbiota of free-ranging and captive rhesus macaques with at least 80% diet similarity to test the hypothesis that hosts in difference environments will have different gut microbiomes despite a shared diet. Although we found that location was a significant predictor of gut microbial composition, the magnitude of observed differences was relatively small. These patterns suggest that a shared diet may limit the typical influence of environmental microbial exposure on the gut microbiota.

The faecal metabolome of black howler monkeys (Alouatta pigra) varies in response to seasonal dietary changes.

Mammals rely on the metabolic functions of their gut microbiota to meet their energetic needs and digest potentially toxic components in their diet. The gut microbiome plastically responds to shifts in host diet and may buffer variation in energy and nutrient availability. However, it is unclear how seasonal differences in the gut microbiome influence microbial metabolism and nutrients available to hosts. In this study, we examine seasonal variation in the gut metabolome of black howler monkeys (Alouatta pigra) to determine whether those variations are associated with differences in gut microbiome composition and nutrient intake, and if plasticity in the gut microbiome buffers shortfalls in energy or nutrient intake. We integrated data on the metabolome of 81 faecal samples from 16 individuals collected across three distinct seasons with gut microbiome, nutrient intake and plant metabolite consumption data from the same period. Faecal metabolite profiles differed significantly between seasons and were strongly associated with changes in plant metabolite consumption. However, microbial community composition and faecal metabolite composition were not strongly associated. Additionally, the connectivity and stability of faecal metabolome networks varied seasonally, with network connectivity being highest during the dry, fruit-dominated season when black howler monkey diets were calorically and nutritionally constrained. Network stability was highest during the dry, leaf-dominated season when most nutrients were being consumed at intermediate rates. Our results suggest that the gut microbiome buffers seasonal variation in dietary intake, and that the buffering effect is most limited when host diet becomes calorically or nutritionally restricted.

Butyrate Production Pathway Abundances Are Similar in Human and Nonhuman Primate Gut Microbiomes.

Over the course of human evolution, shifts in dietary practices such as meat-eating and cooking, have resulted in reduced fiber intake, a trend that has been exaggerated more recently in industrialized populations. Reduced fiber consumption is associated with a loss of gut microbial taxa that degrade fiber, particularly butyrate. Therefore, this dietary shift in humans may have altered the abundance of microbial genes involved in butyrate production. This study uses a gene-targeted alignment approach to quantify the abundance of butyrate production pathway genes from published wild nonhuman primate and human gut metagenomes. Surprisingly, humans have higher diversity and relative abundances of butyrate production pathways compared with all groups of nonhuman primates except cercopithecoids. Industrialized populations of humans also differ only slightly in butyrate pathway abundance from nonindustrialized populations. This apparent resilience of butyrate production pathways to shifts in human diet across both evolutionary and modern populations may signal an evolutionary shift in host-microbe interactions in humans that increased SCFA production. Such a shift could have contributed to meeting the increased energy requirements of humans relative to nonhuman primates.

Comparing different sample collection and storage methods for field-based skin microbiome research.

OBJECTIVES: The skin, as well as its microbial communities, serves as the primary interface between the human body and the surrounding environment. In order to implement the skin microbiome into human biology research, there is a need to explore the effects of different sample collection and storage methodologies, including the feasibility of conducting skin microbiome studies in field settings. METHODS: We collected 99 skin microbiome samples from nine infants living in Veracruz, Mexico using a dual-tipped "dry" swab on the right armpit, palm, and forehead and a "wet" swab (0.15 M NaCl and 0.1% Tween 20) on the same body parts on the left side of the body. One swab from each collection method was stored in 95% ethanol while the other was frozen at -20°C. 16S rRNA amplicon sequencing generated data on bacterial diversity and community composition, which were analyzed using PERMANOVA, linear mixed effects models, and an algorithm-based classifier. RESULTS: Treatment (wet_ethanol, wet_freezer, dry_ethanol, and dry_freezer) had an effect (~10% explanatory power) on the bacterial community diversity and composition of skin samples, although body site exhibited a stronger effect (~20% explanatory power). Within treatments, the collection method (wet vs. dry) affected measures of bacterial diversity to a greater degree than did the storage method (ethanol vs. freezer). CONCLUSIONS: Our study provides novel information on skin microbiome sample collection and storage methods, suggesting that ethanol storage is suitable for research in resource-limited settings. Our results highlight the need for future study design to account for interbody site microbial variation.

The gut microbiome as an indicator of habitat disturbance in a Critically Endangered lemur.

BACKGROUND: Habitat disturbance affects the biology and health of animals globally. Understanding the factors that contribute to the differential responses of animals to habitat disturbance is critical for conservation. The gut microbiota represents a potential pathway through which host responses to habitat disturbance might be mediated. However, a lack of quantitative environmental data in many gut microbiome (GM) studies of wild animals limits our ability to pinpoint mechanisms through which habitat disturbance affects the GM. Here, we examine the impact of anthropogenic habitat disturbance on the diet and GM of the Critically Endangered black-and-white ruffed lemur (Varecia variegata editorum). We collected fecal samples and behavioral data from Varecia occupying habitats qualitatively categorized as primary forest, moderately disturbed forest, and heavily disturbed forest. RESULTS: Varecia diet and GM composition differed substantially across sites. Dietary richness predicted GM richness across sites, and overall GM composition was strongly correlated to diet composition. Additionally, the consumption of three specific food items positively correlated to the relative abundances of five microbial strains and one microbial genus across sites. However, diet did not explain all of the GM variation in our dataset, and differences in the GM were detected that were not correlated with diet, as measured. CONCLUSIONS: Our data suggest that diet is an important influence on the Varecia GM across habitats and thus could be leveraged in novel conservation efforts in the future. However, other factors such as contact with humans should also be accounted for. Overall, we demonstrate that quantitative data describing host habitats must be paired with GM data to better target the specific mechanisms through which environmental change affects the GM.

The relationship between pinworm (Trypanoxyuris) infection and gut bacteria in wild black howler monkeys (Alouatta pigra).

Gut bacteria may coexist with other groups of organisms, such as nematode parasites, that inhabit the gastrointestinal tract of primates; however, the possible effects of endoparasites on bacterial communities are frequently overlooked. Here we explored whether infection with Trypanoxyuris, an oxyurid gastrointestinal parasite, is associated with changes in the gut bacterial community of wild black howler monkeys (Alouatta pigra), by comparing gut bacterial communities of consistently infected individuals and individuals that never tested positive for Trypanoxyuris throughout different months across the year. We additionally controlled for other sources of variation reported to influence the primate microbiome including individual identity, social group, and seasonality. Trypanoxyuris infection was not related to differences in gut bacterial alpha diversity, but was weakly associated with differences in gut bacterial community structure. In contrast, among the covariates considered, both individual identity and social group were more strongly associated with variation in the howler gut bacterial community. Our results suggest that gastrointestinal parasites may be associated, to some extent, with shifts in the gut bacterial communities hosted by free-ranging primates, although a causal link still needs to be established. Further studies of wild primate hosts infected with parasite species with different pathogenicity are needed to better elucidate health-related consequences from the parasite-microbiome interplay.

Assessing the Influence of Environmental Sources on the Gut Mycobiome of Tibetan Macaques.

The distribution and availability of microbes in the environment has an important effect on the composition of the gut microbiome of wild vertebrates. However, our current knowledge of gut-environmental interactions is based principally on data from the host bacterial microbiome, rather than on links that establish how and where hosts acquire their gut mycobiome. This complex interaction needs to be clarified. Here, we explored the relationship between the gut fungal communities of Tibetan macaques (Macaca thibetana) and the presence of environmental (plant and soil) fungi at two study sites using the fungal internal transcribed spacer (ITS) and next generation sequencing. Our findings demonstrate that the gut, plant and soil fungal communities in their natural habitat were distinct. We found that at both study sites, the core abundant taxa and ASVs (Amplicon Sequence Variants) of Tibetan macaques' gut mycobiome were present in environmental samples (plant, soil or both). However, the majority of these fungi were characterized by a relatively low abundance in the environment. This pattern implies that the ecology of the gut may select for diverse but rare environmental fungi. Moreover, our data indicates that the gut mycobiome of Tibetan macaques was more similar to the mycobiome of their plant diet than that present in the soil. For example, we found three abundant ASVs (Didymella rosea, Cercospora, and Cladosporium) that were present in the gut and on plants, but not in the soil. Our results highlight a relationship between the gut mycobiome of wild primates and environmental fungi, with plants diets possibly contributing more to seeding the macaque's gut mycobiome than soil fungi.

The human gut microbiome and health inequities.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.

Captivity Is Associated With Gut Mycobiome Composition in Tibetan Macaques (Macaca thibetana).

Although recent studies have revealed that gut fungi may play an important functional role in animal biology and health, little is known concerning the effects of anthropogenic pressures on the gut mycobiome. Here, we examined differences of the gut mycobiome in wild and captive populations of Tibetan macaques (Macaca thibetana) targeting the fungal internal transcribed spacer (ITS) and using next generation sequencing. Our findings demonstrate that the diversity, composition, and functional guild of the Tibetan macaque gut mycobiome differ across populations living in different habitats. We found that Tibetan macaques translocated from the wild into a captive setting for a period of 1 year, were characterized by a reduction in fungal diversity and an increase in the abundance of potential gut fungal pathogens compared to wild individuals. Furthermore, we found that the relative abundance of two main fungal guilds of plant pathogens and ectomycorrhizal fungi was significantly lower in captive individuals compared to those living in the wild. Our results highlight that, in addition to bacteria, gut fungi vary significantly among individuals living in captive and wild settings. However, given limited data on the functional role that fungi play in the host's gut, as well as the degree to which a host's mycobiome is seeded from fungi in the soil or ingested during the consumption of plant and animal foods, controlled studies are needed to better understand the role of the local environment in seeding the mycobiome.