Cornell researcher Raina Plowright and her team observed that when bats in Australia lost access to their habitat and natural food sources, they sought food on agricultural lands. And when the animals’ diets changed, they shed more virus, increasing the virus’ spread to horses, as well as the risk to people.
A [new study](https://royalsocietypublishing.org/doi/10.1098/rspb.2024.2482), published Feb. 19 in the Proceedings of the Royal Academy B: Biological Sciences, begins to explain why and how the bats’ non-native diets increased viral shedding.
Working with Jamaican fruit bats as models, the team found that a low-protein suboptimal diet, like the mandarins or cocos-palm fruit bats consume after loss of native habitat, causes the bats to shed more virus for a longer duration. The researchers also found that the bats ate more food on these suboptimal diets, behavior that may correlate to more foraging, greater movement and increased spillover of virus into other hosts.
“In our field studies, we observed a connection between eating poor-quality foods, increased shedding of Hendra virus and subsequent spillover of the virus into horses, but there had been no work on the immunological mechanisms,” said [Plowright](https://www.vet.cornell.edu/research/raina-plowright-phd-ms-bvsc), the Rudolf J. and Katharine L. Steffen Professor of Veterinary Medicine in the College of Veterinary Medicine and scholar in the Cornell Atkinson Center for Sustainability. “We took this question to the laboratory and discovered this stunning result: diet had a profound effect on the animals’ ability to clear a virus.”
Broadly, the research warns of the impact of climate change and land development on the behavior and health of bats – animals known to carry and spread deadly viruses, including the progenitors of SARS-CoV-2 (which causes COVID-19), SARS-CoV-1 (which caused the 2003 SARS outbreak), Nipah, Hendra and Ebola – and the increasing risk of spillover, outbreaks and pandemics.
“Some of these viruses are incredibly lethal, yet we continue to clear the land, change the climate and disrupt ecosystems – stressing these animals, removing their food sources and creating new interfaces between wildlife and humans. All of this increases the risk of spillover,” Plowright said. ”In the lab, we used a virus that doesn’t cause disease in humans, but our findings provide a framework to better understand the pathogens that pose a real threat.”
A multi-institution team designed the study, including behavioral ecologists, immunologists, virologists and statisticians. The co-first authors and postdoctoral researchers Caylee Falvo, Ph.D. ’24, and Daniel Crowley, Ph.D. ‘24, fed the captive Jamaican fruit bats three distinct diets: a diet high in sugar and protein that is similar to what the bats would standardly eat; a diet low in protein, analogous to eating fruit such as mandarins; and a diet high in fat, analogous to consuming high-fat fruits like cocos-palm. They then tracked, in metabolic detail, how the bats responded when infected with a strain of influenza endemic in bats.
The bats on the low-protein diet shed more virus for longer while, surprisingly, the bats on the high-fat diet shed less virus for a shorter duration than even the standard diet.
“We think this is a first step in showing how sensitive the bats are to a change in their diets, and thatdifferent diets can change viral shedding patterns,” Falvo said. “We’re now trying to dig into the data more, to understand why they responded in that way and whether that response is comparable in other species.”
Falvo said that while the bats on the high-fat diet shed less virus, that advantage, in terms of spillover, might be offset by increased foraging and any long-term health effects.
“So maybe they shed virus for less time, but because they need to eat more food, the exposure risk might be higher because the bats are moving around the landscape,” she said. “We also don’t know what this means for their longer-term health or immune response.”
They found evidence that the diets altered the gut metabolites of the bats and made them more or less prepared to fend off the influenza virus. In the case of the high-fat diet, the amino acid citrulline seemed to play an important role in boosting immune function, but further studies are needed to understand the mechanisms.
“We had this giant, complex metabolomic dataset, but it looked like this one metabolite, citrulline, was really important compared to all the others,” Crowley said. “Now we’re doing a follow-up study where we’re taking that one metabolite and manipulating it to see if we can influence viral shedding.”
Falvo, Crowley and other team members are also taking the data back into the field to track the bats’ foraging behavior, to see if bats’ higher intake of food corresponds to more widespread movement.
“We try as much as possible to have this iterative process, where we spend a lot of time in the field, develop hypotheses, and then try to test some piece of that experimentally,” Falvo said. “Then, from what we’ve learned in the lab, we go back to the field – we do that repeatedly with a massive team of experts that make it possible.”
The researchers said the study is further evidence that preventing the next pandemic – which they said could be much more deadly than COVID-19 – must include plans to preserve and restore natural habitats and food sources.
“We’re in an extraordinary situation right now, where we are actively dismantling our ability to detect and respond to the next pandemic, even as we accelerate our expansion into the natural world – disrupting ecosystems, displacing wildlife and increasing our exposure to new viruses. Many who lived through COVID have grown complacent, assuming it was the worst a pandemic could be. But the reality is that nature harbors an enormous diversity of viruses, some with fatality rates exceeding 50%, even 70%. The next pandemic could be far deadlier,” Plowright said. “We must protect the world’s remaining intact wild areas, restore ecosystems where possible and take proactive measures to stop these viruses from spilling over into humans in the first place.“
Co-authors include Evelyn Benson, Monica N. Hall, Madison Hebner and co-senior author Agnieszka Rynda-Apple of Montana State University; Benjamin Schwarz and Eric Bohrnsen of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH); Manuel Ruiz-Aravena, a former postdoctoral researcher now at Mississippi State University; Wenjun Ma of the University of Missouri; and Tony Schountz of Colorado State University.
The study was supported with funding from the National Science Foundation, the NIH and DARPA.