In a study on mice with a simplified version of the human microbiome, scientists showed that B. wadsworthia takes advantage of diets rich in animal fat by reprogramming its metabolism. This allows it to outcompete other gut microbes and flourish.

However, this microbial success story has a downside for its host as these bacteria have been linked to conditions such as Inflammatory bowel disease, colorectal cancer and metabolic liver disease, especially in people consuming Western-style diets.

B. wadsworthia is a common feature of the gut microbiome, the complex community of microbes living in our colon that has a major impact on health. 50-60% of people have it in their personal microbiome, and for most of them, it is benign. However, blooms of B. wadsworthia are often seen in people who eat diets high in animal-derived fats.

B. wadsworthia obtains its energy primarily from taurine, a sulfur-containing compound that it derives from meat and seafood that we eat. In that process, it releases hydrogen sulfide, a gas we most associate with the rotten egg smell. While small amounts of hydrogen sulfide are normal and even beneficial in the gut, large quantities can damage the gut lining and trigger inflammation. An overgrowth of these bacteria could be contributing to colonic and liver disease, but how this happens and the links to disease aren’t clear.

To better understand this, researchers from the Quadram Institute set out to investigate the interactions between B. wadsworthia, diet and the other microbes in the gut that compete and collaborate with each other, to work out the secrets of its colonisation strategy.

To capture the complexity of these dynamic interactions and how they affect their host, the team introduced a simplified version of the human microbiome into mice that had been grown microbe-free. This contains a group of representative species that together carry out the normal healthy functions of the gut microbiome. One group of mice also received B. wadsworthia, and another group were only colonised with B. wadsworthia.  The mice were fed on a milk-derived high-fat diet, to mimic the animal-derived high-fat diet linked to poor health in humans.

The researchers used multiple techniques, including TraDIS and metatranscriptomics, to understand which genes B. wadsworthia turns on to colonise the gut in the presence or absence of the microbiome. They then looked to link these changes back to the health of the host.

Transmission electron microscopy image of Bilophila wadsworthia cell with cluster of microcompartments (circled). Image by Michael Paxhia, University of Kent microscopy facility

The research team discovered that B. wadsworthia forms tiny “factory” structures called bacterial microcompartments inside its cells to be able to colonise the gut. These structures act as protective capsules, to safely containing the toxic by-products of its metabolism to break down taurine.

Interestingly, when B. wadsworthia shares the gut with other microbes, it changes its strategy. It switches to fermenting alternative energy sources, such as formate and pyruvate, and begins producing ethanol. This adaptation gives it a competitive edge—but again, at a cost to the host.

The presence of ethanol and hydrogen sulfide together was linked to increased gut permeability and higher levels of liver inflammation. The researchers also observed a depletion in protective gut metabolites like short-chain fatty acids and inosine—substances normally produced by a healthy microbiome. Inosine is thought to play a role in protecting against alcohol-induced liver injury, which would exacerbate the effects of the excess ethanol.

Ethanol produced by gut bacteria can enter the liver through the gut-liver axis, where it contributes to liver stress and inflammation. This microbial ethanol may disrupt bile acid balance, damage liver cells, and promote the development of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), similar to what happens with alcohol-related liver injury—even in people who don’t drink alcohol.

The researchers now think that it is the combination of these factors that ties B. wadsworthia to the harmful effects of a high-fat diet on the body.

Understanding how B. wadsworthia adapts and affects the gut environment is an important step toward preventing diet-associated diseases like liver inflammation and gut barrier dysfunction.

“We’ve uncovered the metabolic tricks this bacterium uses to thrive in the gut—and how those tricks come at the host’s expense,” said Dr Lizbeth Sayavedra from the Quadram Institute, first and lead author of the study.

“By identifying the conditions that allow B. wadsworthia to become harmful, we can begin to think about targeted strategies—like diet, probiotics, or even microbiome editing—to keep it in check and protect against disease.”

The study was funded by the Biotechnology and Biological Science Research Council, part of UKRI.

Reference: Bacterial microcompartments and energy metabolism drive gut colonization by Bilophila wadsworthia. Sayavedra, L., Yasir, M., Goldson, A. et al. Nature Communications 16, 5049 (2025). DOI: 10.1038/s41467-025-60180-y