The modern Western-style diet—high in processed foods, red meat, dairy products, and sugar—alters the composition of the gut microbiome in ways that can have a huge impact on health. This dietary pattern, which is also low in fruits, vegetables and whole grains, reduces the variety of microbes in the digestive system and the molecules they produce.

In new research published in Nature, researchers from the University of Chicago show how mice that have been fed a Western-style diet are not able to rebuild a “healthy,” diverse gut microbiome following antibiotic treatment. These mice were also more susceptible to infection by pathogens such as Salmonella.

On the other hand, mice given food loosely mimicking a Mediterranean diet—high in plant-based fiber from fruits, vegetables and whole grains—were able to quickly restore a healthy and resilient gut microbiome after antibiotics.

“We were really surprised by how dramatically different the recovery process is in the mice on the Western-style diet versus the healthier one,” said Megan Kennedy, a student in the Medical Scientist Training Program at UChicago and lead author of the study.

Rebuilding after a forest fire

Antibiotics can have a devastating effect on the gut microbiome. Though often given to treat infections by specific pathogens, these drugs are indiscriminate. As a side effect, they can wipe out entire communities of bacteria—both the bad ones causing disease and the good, commensal ones that help keep us healthy long-term.

Eugene B. Chang, the Martin Boyer Professor of Medicine at UChicago and a senior author on the study, likens this to a forest fire, suggesting natural rules of ecology apply when rebuilding the community of bacteria in the gut. 

“The mammalian gut microbiome is like a forest, and when you damage it, it must have a succession of events that occur in a specific order to restore itself back to its former health,” Chang said. “When you are on a Western diet, this does not happen because it doesn’t provide the nutrients for the right microbes at the right time to recover.”

“Instead, you end up with a few species that monopolize these resources and don’t set the stage for other organisms that are required for recovery,” he said.

“We were really surprised by how dramatically different the recovery process is in the mice on the Western-style diet versus the healthier one,” said lead author Megan Kennedy, a student in the Medical Scientist Training Program at UChicago.

They started with mice that were fed with food mimicking a typical modern diet or a “mouse chow” with diverse sources of plant fiber and low fat. Both groups were then treated with antibiotics. Later, some mice continued the same diet, while others were switched to the different diet.

The researchers also reintroduced microbes to the mice after antibiotics through fecal microbial transplants. The rationale behind using these transplants is that it can restore a healthy equilibrium in the gut by transferring microbes in the stool from one healthy animal to another. 

When the researchers analyzed the makeup of microbes in these different test groups, they saw that only the mice on the plant fiber-rich diet, either before or after antibiotics, were able to recover to a healthy equilibrium of microbes. Further analysis by Christopher Henry, a computational biologist at Argonne National Laboratory, and his group showed that this diet promotes networks of metabolites that set the stage for microbes to rebuild a healthy ecosystem. 

In contrast, fecal microbial transplants had a negligible impact on recovery among the mice on Western diets after antibiotics. These mice were also susceptible to infection with Salmonella, a common intestinal pathogen.

“It doesn’t seem to matter what microbes you’re putting into the community through a fecal microbial transplant, even if it’s matched in every way possible to the ideal transplant,” Kennedy said. “If the mice are on the wrong diet, the microbes don’t stick, the community doesn’t diversify and it doesn’t recover.”

Eat your fruit and vegetables, again

Kennedy and Chang say this shows how diet builds the crucial foundation for a diverse, robust and resilient gut microbiome. 

Besides promoting overall good health, one potential clinical application is using diet to treat infections in patients following cancer treatment or organ transplants. These patients are often placed on powerful antibiotics and immunosuppressant drugs, which can lead to infections with multidrug-resistant bacteria. 

Adding more antibiotics would only compound the situation. 

“Maybe we can [instead] use diet to rebuild the commensal microbes that have been suppressed under these therapies,” Chang said. “We can restore the healthy microbiome much quicker and prevent the emergence of more multidrug-resistant organisms.”

Despite the new details on how diet changes the gut microbiome, the study also repeats the same message parents have been telling their kids since time immemorial: Eat your fruits and vegetables, they’re good for you. 

But both researchers also recognize they can’t expect everyone to become vegans overnight for the sake of their health.

Kennedy suggests that people could think about adding more healthy foods to their diet to prepare for an upcoming surgery when they know they’ll be taking antibiotics. Chang is also working on what he calls a “have your cake and eat it too” approach, where people could take custom supplements to bolster their gut health, even if they don’t drastically change their diet.

“I’ve become a believer that food can be medicinal,” Chang said. “In fact, I think that food can be prescriptive, because we can ultimately decide what food components are affecting which populations and functions of the gut microbiome.”

Reference: Kennedy MS, Freiburger A, Cooper M, et al. Diet outperforms microbial transplant to drive microbiome recovery in mice. Nature. 2025. doi: 10.1038/s41586-025-08937-9

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