Western Diet Disrupts Gut Recovery and Raises Infection Risk

A high-fat, low-fiber Western-style diet severely impairs the gut microbiome’s ability to recover from antibiotic treatment, potentially leaving individuals vulnerable to dangerous infections, according to research from the University of Chicago published this week in Nature.

The study reveals that mice consuming a Western diet experienced prolonged microbiome disruption after antibiotics, while those eating fiber-rich foods recovered quickly through a natural succession process that restored microbial diversity and protective functions.

“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, lead author and student in the Medical Scientist Training Program at UChicago.

The research team, led by Eugene B. Chang, MD, Martin Boyer Professor of Medicine at UChicago, found that mice on regular chow diet (high in plant fibers, low in fat) rebuilt their gut microbial communities rapidly after antibiotic treatment through a carefully orchestrated series of ecological steps. In contrast, mice on Western diets (high fat, low fiber) remained in a severely disrupted state for at least nine weeks.

This disruption left the Western diet mice vulnerable to infection by Salmonella, an intestinal pathogen that normally can’t establish infection in mice with healthy gut communities.

The investigators employed sophisticated metabolic modeling to uncover why the dietary environment so profoundly impacts recovery. Their analysis revealed that fiber-rich diets promote beneficial cross-feeding relationships between different bacterial species – essentially creating an ecosystem where microbes support each other’s growth through metabolic byproducts.

Western diets, however, promote dominance by a single bacterial strain that monopolizes available nutrients without supporting community diversity. This ecological imbalance prevents the development of a healthy, complex microbial community that can resist pathogens.

Chang likens the antibiotics’ effect on gut bacteria to a forest fire. “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,” he explained. “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.”

Perhaps most surprisingly, the research team found that fecal microbiota transplant (FMT) – a procedure that introduces healthy bacteria from a donor – was ineffective at restoring microbial communities in mice on Western diets. Only dietary intervention successfully restored microbiome health.

“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 noted. “If the mice are on the wrong diet, the microbes don’t stick, the community doesn’t diversify, and it doesn’t recover.”

The findings represent a paradigm shift in our understanding of microbiome restoration. While FMT has gained popularity as a treatment for stubborn gut infections, this study suggests that dietary intervention may be a more fundamental approach for microbiome recovery.

The research carries significant implications for human health, particularly given Americans’ high consumption of Western-style diets and frequent antibiotic use. Patients undergoing cancer treatments or organ transplants, who often receive multiple courses of antibiotics, might particularly benefit from dietary interventions that rebuild healthy gut communities.

The study also highlights the potential of food as medicine. “I’ve become a believer that food can be medicinal,” said Chang. “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.”

For individuals about to undergo antibiotic treatment, the research suggests increasing consumption of fiber-rich foods like fruits, vegetables and whole grains might help their gut microbiome recover more quickly afterward.

Researchers are now exploring methods to achieve similar benefits without drastic dietary changes, potentially through targeted supplements that support microbiome recovery even with suboptimal diets.

The study 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.