The latest western-style diet, rich in processed foods, lean meat, dairy products and sugar, is hindering the composition of the gut microbiota in ways that can have a major impact on health. This dietary pattern also low in fruits, vegetables and whole grains reduces the various microorganisms of the digestive system and the molecules they produce.
A new study published in Nature shows that mice fed western-style diets are unable to reconstruct their healthy, diverse gut microbiota after antibiotic treatment. These mice are now more susceptible to infections by pathogens such as salmonella.
Meanwhile, mice that roughly mimic the Mediterranean diet were able to quickly recover healthy and resilient gut microbiota after antibiotics – a high in plant-based fiber from fruits, vegetables and whole grains.
“I was really surprised at how dramatically the recovery process is different between western-style and healthier-eating mice,” said Megan Kennedy, a student at Uchicago's Medical Scientist Training Program and a lead author of the study.
Rebuild after a bushfire
Antibiotics can have devastating effects on the gut microbiota. Although often given to treat infections caused by certain pathogens, these drugs are indiscriminate. As a side effect, they can wipe out the entire bacterial community. This means that we can cause bad things that cause illness and good symbiosis that help us stay healthy for the long term.
Eugene B. Chan, professor of medicine at Uchikago and senior author of the study, likened this to forest fires, suggesting that natural rules of ecology apply when reconstructing bacterial communities in the gut.
“The mammalian gut microbiota is like a forest, and if it is damaged, it requires a series of events that occur in a certain order to return to its previous health,” Chan said. “When you're on a Western diet, this doesn't happen because you don't provide the right microbial nutrients to recover at the right time.”
“Instead, it will be some species that monopolize these resources and do not set the stages of other organisms needed for recovery,” he said.
Antibiotics and highly processed foods are both common in the US, and Kennedy and Chan have come to explore how this combination of microbiome disintegration practices affects gut health.
They started with foods that mimic the typical modern diet and mice mimic “mouse chow” with diverse plant fiber and low-fat sources. Both groups were then treated with antibiotics. Some mice then continued on the same diet, while others were switched to different diets.
The researchers also reintroduced the microorganisms into mice following antibiotics via fecal microorganism transplantation. The rationale behind using these implants is that by transferring stool microbes from one healthy animal to another, healthy gut balance can be restored.
When researchers analyzed the composition of microorganisms in these different test groups, they saw that only mice in a diet rich in plant fiber before or after antibiotics can recover to a healthy equilibrium of microorganisms. Further analysis by Christopher Henry, a computational biologist at the Argonne National Laboratory, and his group showed that this diet promotes a network of metabolites that set the stages of microorganisms to reconstruct healthy ecosystems.
In contrast, fecal microbial transplantation had a negligible effect on recovery in Western diet mice following antibiotics. These mice were also susceptible to infection with Salmonella, a common intestinal pathogen.
“It doesn't seem to matter which microorganisms are being put into the community through fecal microorganism transplantation, even if it matches the ideal transplant in every possible way,” Kennedy said. “If mice are eating the wrong diet, microbes don't stick, communities don't diversify and they don't recover.”
Eat fruits and vegetables again
Kennedy and Chan say this shows how the diet builds an important foundation for a diverse, robust and resilient gut microbiota.
In addition to promoting overall health, one potential clinical application is the use of diet to treat cancer or to treat infections in patients after organ transplantation. These patients are often placed on potent antibiotics and immunosuppressants, which can lead to infections caused by multidrug resistant bacteria.
Increased antibiotics will only make the situation worse.
“Maybe we can [instead] Chang uses diet to reconstruct symbiotic microorganisms that are suppressed under these treatments.
Despite new details about how diet changes the intestinal microbiome, the study also repeats the same messages parents have been passing on to their children since ancient times. Eat your fruits and vegetables and they are good for you.
However, both researchers realize that no one can expect to become vegan overnight for health.
Kennedy suggests that when people know they will take antibiotics, they can consider adding healthy foods to their diet to prepare for future surgeries. Chang is also working on what he calls the “eat with a cake” approach. There, people can take custom supplements to enhance their gut health without having to significantly change their diet.
“I believe food is medicinal,” Chan said. “In fact, I think foods are normative because they can ultimately determine which food ingredients affect which populations and which groups and functions of the gut microbiome.”
Another senior author of the paper is formerly Joy Burgelson of Uchicago, now Silver Professor of Biology at New York University and executive vice president of life sciences at the Simmons Foundation.
Quote: “Diets outweigh microbial transplants and promotes recovery of the mice's microbial flora,” Kennedy et al., Nature, April 30, 2025.
Funding: US Department of Energy's Simons Foundation, Chicago's Gastrointestinal Research Foundation, and National Institutes of Health. Hong Kong China University collaborators were funded by Hong Kong's Council of Innovation and Technology.
– Recruited from the article first published by the Biological Sciences Department.
