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.

Age-related changes in hematological biomarkers in common marmosets.

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC) change with age in common marmosets (Callithrix jacchus). We assessed blood samples collected during routine physical exams at the Southwest National Primate Research Center and the University of Texas Health San Antonio marmoset colonies from November 2020-November 2021. We found that chemistry and CBC profiles varied based on facility, sex, and age. Significant changes in albumin, phosphorus/creatinine ratio, albumin/globulin ratio, amylase, creatinine, lymphocyte percent, hematocrit, granulocytes percent, lymphocytes, hemoglobin, red cell distribution width, and platelet distribution width were all reported with advancing age. Aged individuals also demonstrated evidence for changes in liver, kidney, and immune system function compared with younger individuals. Our results suggest there may be regular changes associated with healthy aging in marmosets that are outside of the range typically considered as normal values for healthy young individuals, indicating the potential need for redefined healthy ranges for clinical biomarkers in aged animals. Identifying animals that exhibit values outside of this defined healthy aging reference will allow more accurate diagnostics and treatments for aging colonies.

A comparison of faecal glucocorticoid metabolite concentration and gut microbiota diversity in bonobos (Pan paniscus).

Sex, age, diet, stress and social environment have all been shown to influence the gut microbiota. In several mammals, including humans, increased stress is related to decreasing gut microbial diversity and may differentially impact specific taxa. Recent evidence from gorillas shows faecal glucocorticoid metabolite concentration (FGMC) did not significantly explain gut microbial diversity, but it was significantly associated with the abundance of the family Anaerolineaceae. These patterns have yet to be examined in other primates, like bonobos (Pan paniscus). We compared FGMC to 16S rRNA amplicons for 202 bonobo faecal samples collected across 5 months to evaluate the impact of stress, measured with FGMC, on the gut microbiota. Alpha diversity measures (Chao's and Shannon's indexes) were not significantly related to FGMC. FGMC explained 0.80 % of the variation in beta diversity for Jensen-Shannon and 1.2% for weighted UniFrac but was not significant for unweighted UniFrac. We found that genus SHD-231, a member of the family Anaerolinaceae had a significant positive relationship with FGMC. These results suggest that bonobos are relatively similar to gorillas in alpha diversity and family Anaerolinaceae responses to FGMC, but different from gorillas in beta diversity. Members of the family Anaerolinaceae may be differentially affected by FGMC across great apes. FGMC appears to be context dependent and may be species-specific for alpha and beta diversity but this study provides an example of consistent change in two African apes. Thus, the relationship between physiological stress and the gut microbiome may be difficult to predict, even among closely related species.

A Test of Foraging Models Using Dietary Diversity Indices for the Lomako Forest Bonobos.

Optimal diet and functional response models are used to understand the evolution of primate foraging strategies. The predictions of these models can be tested by examining the geographic and seasonal variation in dietary diversity. Dietary diversity is a useful tool that allows dietary comparisons across differing sampling locations and time periods. Bonobos (Pan paniscus) are considered primarily frugivorous and consume fruits, leaves, insects, vertebrates, terrestrial herbaceous vegetation, and flowers. Frugivores, like bonobos, are valuable for examining dietary diversity and testing foraging models because they eat a variety of species and are subject to seasonal shifts in fruit availability. Frugivorous primate species thus allow for tests of how variation in dietary diversity is correlated with variation in ecological factors. We investigated measures of dietary diversity in bonobos at two research camps across field seasons within the same protected area (N'dele and Iyema) in Lomako Forest, Democratic Republic of the Congo. We compared the results of behavioral observation (1984/1985, 1991, 1995, 2014, and 2017) and fecal washing analysis (2007 and 2009) between seasons and study period using three diversity indices (Shannon's, Simpson's, and SW evenness). The average yearly dietary diversity indices at N'dele were Shannon's H' = 2.04, Simpson's D = 0.82, and SW evenness = 0.88 while at Iyema, the indices were Shannon's H' = 2.02, Simpson's D = 0.82, and SW evenness = 0.88. Behavioral observation data sets yielded significantly higher dietary diversity indices than fecal washing data sets. We found that food item (fruit, leaf, and flower) consumption was not associated with seasonal food availability for the 2017 behavioral observation data set. Shannon's index was lower during periods when fewer bonobo dietary items were available to consume and higher when fruit was abundant. Finally, we found that optimal diet models best-explained patterns of seasonal food availability and dietary diversity. Dietary diversity is an essential factor to consider when understanding primate diets and can be a tool in understanding variation in primate diets, particularly among frugivores. Dietary diversity varies across populations of the same species and across time, and it is critical in establishing a complete understanding of how primate diets change over time.

Sex differences in bonobo (Pan paniscus) terrestriality: implications for human evolution.

Recent finds in hominin fossil environments place the transition to terrestriality in a wooded or forested habitat. Therefore, forest-dwelling apes can aid in understanding this important evolutionary transition. Sex differences in ape locomotion have been previously attributed to sexual dimorphism or ecological niche differences between males and females. This study examined the hypothesis that differential advantages of terrestrial travel may impact mating success in male bonobos. We examined whether males are more terrestrial when there are mating benefits for fast travel. We analyzed behavioral data on wild bonobos over a ten-month period in the Lomako Forest, DRC and examined the proportion of time spent at lower heights compared to higher heights between adult females and males relative to their location to feeding contexts with high mating frequencies. We found a significant interaction between sex and height class away from food patches (F=4.65, df =1, p <0.05) such that females were primarily arboreal whereas there was no difference between males across height classes. However, there was also a significant interaction between sex and height class (F =29.35, df =1, p <0.0001) for adults traveling near or entering a food patch. Males often arrived at food patches terrestrially and females arrived almost exclusively arboreally. We found a significant difference between the expected and observed distribution of matings by food patch context (G =114.36, df =4, p <0.0001) such that most mating occurred near or in a food patch. These results suggest that males may travel terrestrially to arrive at food patches before cohesive parties of females arrive arboreally, in order to compete with other males for mating access to these females. Such intrasexual selection for sex differences in locomotion may be important in considerations of the evolution of locomotion strategies in hominins in a forested environment.

New Observations of Meat Eating and Sharing in Wild Bonobos (Pan paniscus) at Iyema, Lomako Forest Reserve, Democratic Republic of the Congo.

Bonobos (Pan paniscus) consume a variety of vertebrates, although direct observations remain relatively rare compared to chimpanzees (Pan troglodytes). We report the first direct observations of meat eating and sharing among bonobos at Iyema, Lomako Forest, Democratic Republic of Congo. We collected meat consumption data ad libitum from June to November 2017 over 176.5 observation hours and conducted monthly censuses to measure the abundance of potential prey species. We observed 3 occasions of duiker consumption and found indirect evidence of meat consumption twice (n = 5). We identified the prey species as Weyn's duiker (Cephalophus weynsi) in all 4 cases that we saw the carcass. This species was the most abundant duiker species at Iyema, but other potential prey species were also available. Meat sharing was observed or inferred during all 3 observations. However, the individual controlling the carcass frequently resisted sharing, and aggressive attempts to take the carcass were observed. This report contributes to a growing body of data suggesting that wild bonobos consume meat at higher rates than previously thought, female control of carcasses is frequent but not exclusive, and meat sharing in bonobos is primarily passive but not without aggression.

DNA binding site analysis of Burkholderia thailandensis response regulators.

Bacterial response regulators (RR) that function as transcription factors in two component signaling pathways are crucial for ensuring tight regulation and coordinated expression of the genome. Currently, consensus DNA binding sites in the promoter for very few bacterial RRs have been identified. A systematic method to characterize these DNA binding sites for RRs would enable prediction of specific gene expression patterns in response to extracellular stimuli. To identify RR DNA binding sites, we functionally activated RRs using beryllofluoride and applied them to a protein-binding microarray (PBM) to discover DNA binding motifs for RRs expressed in Burkholderia, a Gram-negative bacterial genus. We identified DNA binding motifs for conserved RRs in Burkholderia thailandensis, including KdpE, RisA, and NarL, as well as for a previously uncharacterized RR at locus BTH_II2335 and its ortholog in the human pathogen Burkholderia pseudomallei at locus BPSS2315. We further demonstrate RR binding of predicted genomic targets for the two orthologs using gel shift assays and reveal a pattern of RR regulation of expression of self and other two component systems. Our studies illustrate the use of PBMs to identify DNA binding specificities for bacterial RRs and enable prediction of gene regulatory networks in response to two component signaling.