K01 Recipient, Jonathan B. Clayton, D.V.M., Ph.D., Investigates the Microbiome’s Influence on Primate Health and Behavior
According to his mother, Dr. Jonathan B. Clayton (Figure 1) has been fascinated by nonhuman primates (NHPs) since he was in diapers. “Even among my primatology friends—they always say, ‘You really like monkeys!’” Dr. Clayton said with a laugh. He attended veterinary school and also earned a Ph.D. before establishing his own laboratory with support from a Special Emphasis Research Career Award (SERCA) in Pathology and Comparative Medicine (K01) award in 2022 from ORIP. Through his research, Dr. Clayton aims to improve our understanding of animal and human gut health while fulfilling his childhood dream of working with monkeys. As an example of planning ahead for success in this goal, he founded the Primate Microbiome Project in 2013. This project is developing a systematic map of variation in microbiome structure and function among NHPs from across the world (Figure 2).
Dr. Clayton realized he wanted to be a veterinarian and work with NHPs when he was majoring in biology at Barton College, a small liberal arts school in eastern North Carolina. He earned his undergraduate degree at Barton College. Subsequently, he received a Certificate in Primatology from Duke University—all before entering a veterinary–doctorate program at the University of Minnesota. During his first summer in the program, Dr. Clayton worked in Dr. Timothy Johnson’s laboratory, which focused on bacterial ecology and the rapidly expanding microbiome field. “Research was where I wanted to go,” explained Dr. Clayton. “It was 2009—right in the sweet spot of the microbiome boom.” His project involved identifying pathogens responsible for bouts of diarrhea among the primates at the Como Park Zoo and Conservatory in Saint Paul, Minnesota. Dr. Clayton reflected that although this work was often challenging, it awakened his lasting interest in the gut health of NHPs.
Dr. Clayton remained in the Johnson laboratory to complete his graduate studies. He spent a year in Vietnam studying endangered monkeys of the Colobinae subfamily. Conservation of these species is challenging because captive populations often suffer from gastrointestinal (GI) illness associated with their unique ruminant-like GI system. In a 2016 study published in Proceedings of the National Academy of Sciences U.S.A., Dr. Clayton and his colleagues showed differences between the microbiomes of wild and captive populations of two NHP species: red-shanked doucs (Pygathrix nemaeus) and mantled howling monkeys (Alouatta palliata).1 Each species exhibited a unique microbiome signature in the wild. However, in captive settings, their gut ecologies converged into a distinct “captive microbiome” that was associated with reduced plant and fiber intake similar to the microbiomes of humans consuming a Western diet. “We went in focused on animal health,” noted Dr. Clayton, “and it evolved into one of the first studies showing how prominently lifestyle effects can alter the microbiome.”
Dr. Clayton joined the University of Nebraska Omaha and University of Nebraska–Lincoln in 2019 as an Assistant Professor of Biology and Assistant Professor of Food Science and Technology, respectively (Figure 3). ORIP’s SERCA K01 award was a perfect fit for a veterinarian hoping to establish a biomedical research program. “Having attended veterinary school with an additional 5 years of Ph.D. education…It was very rigorous,” observed Dr. Clayton. “I wanted to utilize that to my advantage.” His laboratory currently studies host–microbiome interactions in NHP models. His K01-supported project (2022–2027) involves investigating the connection between antibiotic use and neuropsychiatric conditions like depression and anxiety. This relationship has been reported in both animals and humans. To study how antibiotics disrupt the balance of bacteria in the gut (also known as gut dysbiosis) and possible mechanisms by which gut dysbiosis causes psychological changes, his group administered antibiotics to a population of common marmosets (Callithrix jacchus) and observed the resulting physiological and behavioral changes. Animals treated with antibiotics showed significant changes in gut metabolites that serve as neurotransmitters or moderate communication between the gut and the brain. Treated animals also became more sociable (a possible coping mechanism for stress) and had higher levels of urinary cortisol than controls when subjected to a stressor (indicating higher levels of stress). The results were published in Gut Microbes in January 2024.2 Future studies will assess the effects of gut dysbiosis on marmosets, including behavioral changes.
Dr. Clayton shares advice for junior veterinarians interested in a career in biomedicine. He recommends getting early exposure to research—for example, before even applying to veterinary school—and investigating different program options, as well as exploring any associated funding opportunities. “You need to get that exposure early so you can utilize the resources available to succeed,” he emphasized.
Dr. Clayton also expresses gratitude to ORIP for several forms of support, including guidance on the NIH Loan Repayment Program, feedback about his K01 proposal, and networking events for K awardees to focus on future funding opportunities. Describing the importance of the K01 to his career trajectory, Dr. Clayton emphasized that the funding has been an “absolute game changer” for him as an early-career scientist. “The K01 award provides support for training as well as research,” he explained. “To prepare the application for this award, you have to recruit an excellent mentoring team and make sure resources are in place to accomplish what you propose. It is critical to have strong support from your academic institution. All those things—the intangibles, if you will—were, and still are, huge.”
For more information about research training opportunities for veterinarians, please visit ORIP’s Training and Career Development webpages.
References
1Clayton JB, Vangay P, Huang H, et al. Captivity humanizes the primate microbiome. PNAS USA. 2016;113(37):10376–10381. doi:10.1073/pnas.1521835113.
2Hayer SS, Conrin M, French JA, et al. Antibiotic-induced gut dysbiosis elicits gut–brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model. Gut Microbes. 2024;16(1):2305476. doi:10.1080/19490976.2024.2305476.