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 metabolites they produce. This, in turn, increases risk for several immune system-related conditions such as inflammatory bowel disease.
In new research published in Nature, researchers from the University of Chicago show how mice 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 like Salmonella. However, 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. While often given to treat infections by specific pathogens, antibiotics are indiscriminate and can wipe out entire communities of bacteria, both the bad ones causing disease and the good, commensal ones that help keep us healthy.
Eugene B. Chang, MD, Martin Boyer Professor of Medicine at UChicago, a senior author on the study and one of Kennedy's PhD advisors, likens this to a forest fire—meaning that natural rules of ecology apply when rebuilding the community of bacteria in the gut. This analogy is fitting, given that Kennedy's other advisor, Joy Bergelson, PhD, formerly of UChicago, studies how plants interact and co-evolve with microbes. Bergelson, another senior author on the study, is now Silver Professor of Biology at New York University and Executive Vice President of Life Sciences at the Simons Foundation.
"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."
Unfortunately, overuse of antibiotics and the Western diet are common in the United States. This led Kennedy and Chang to explore how this combination of microbiome-disrupting practices affects gut health.
They started with mice that were fed with food mimicking a typical Western-style diet (WD) or a diet of regular mouse chow (RC) with diverse sources of plant fiber and low fat. Both groups were then treated with antibiotics. Later, some mice continued the same diet, while some were switched to the other diet.
The researchers also reintroduced microbes to the mice after antibiotics through fecal microbial transplant (FMT). The rationale behind using FMT is that it can restore a healthy equilibrium in the gut by transferring microbes in the stool from healthy animals to another.
When the researchers analyzed the makeup of microbes in these different test groups, they saw that only the mice on RC, either before or after antibiotics, were able to recover to a healthy equilibrium of microbes. Further analysis by Christopher Henry, PhD, 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.
FMT had a negligible impact on recovery, however, among the mice on WD 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 FMT, 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. Instead, Chang said, "Maybe we can use diet to rebuild the commensal microbes that have been suppressed under these therapies. 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."
The study, "Diet outperforms microbial transplant to drive microbiome recovery in mice," was supported by the National Institutes of Health, the Gastrointestinal Research Foundation of Chicago, the Simons Foundation, the U.S. Department of Energy and collaborators at the Chinese University of Hong Kong funded by the Innovation and Technology Council of Hong Kong.
