Revealing the Relationship Between the Gut Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a common liver condition where excess fat builds up in the liver. Certain gut bacteria have been linked to MASLD, but other components of the gut microbiome—including viruses, fungi and other microbes—have been unexplored.

Understanding the gut microbiome-disease relationship requires more than just identifying what microbes are there. It’s critical we know their function and the mechanisms behind it. To do this, we looked at transcribing microbes and the metabolites they produce. We also integrated advanced molecular profiling of the microbiome.

Q: What knowledge gap does your study help to fill?

We aimed to better understand how different components of the gut microbiome, and their interactions, may influence MASLD.

Q: What methods or approach did you use?

We analyzed stool samples from participants in the long-running Nurses’ Health Study II. These samples were used to create bug, transcript and metabolite profiles of the gut microbiome using state-of-the-art sequencing techniques and cutting-edge bioinformatics tools for downstream analyses.

Q: What did you find?

We found microbes normally found in the mouth, such as Streptococcus, were more common in the gut of individuals with MASLD—especially in those who were overweight or obese. This pattern mirrors what has been seen in other inflammatory conditions, such as inflammatory bowel disease.

We also saw that these differences between groups came with changes in microbial activity and the metabolites they produce. Interestingly, we discovered changes in gut viruses—particularly bacteriophage (viruses that infect bacteria)—which corresponded with bacterial changes identified in MASLD.

Q: What are the implications?

Our findings suggest that for individuals with MASLD, oral bacteria may move to the gut and disrupt the gut microbial communities. We also found that changes in the microbiome differ depending on whether the person with MASLD is lean or overweight. Our work highlights the importance of gut viruses, which have been largely understudied in liver disease research.

Q: What are the next steps?

We shared all our data publicly as a resource for other researchers. Future studies may examine how different parts of the gut microbiome contribute to MASLD and other chronic diseases.