A recent study from researchers at the University of California San Diego has found that time-restricted feeding (TRF) can restore the rhythmic activity of the gut microbiome, offering a potential strategy to combat metabolic diseases linked to high-fat diets.

Over an eight-week experimental period, TRF demonstrated protective effects against metabolic dysfunction in mice, while also restoring daily rhythms in microbial gene activity that traditional methods failed to detect.

Utilizing metatranscriptomics, the researchers analyzed daily fluctuations in microbial gene expression and discovered that TRF not only alters the presence of microbes but also modifies their activity patterns, influencing metabolism.

The findings imply that similar enzymes may exist in humans, suggesting promising applications for improving human health.

Published in the journal Cell Host & Microbe on June 18, 2025, this study involved multiple co-authors from UC San Diego and other institutions.

The research points to the potential for targeted microbial therapies to treat obesity, diabetes, and other metabolic diseases by leveraging time-sensitive microbial functions.

Future research is set to explore engineered bacteria in models of obesity and diabetes to confirm the metabolic benefits and investigate additional time-sensitive microbial genes for targeted therapies.

This study underscores the importance of not only what we eat but also when we eat, highlighting the timing of food intake as a critical factor for metabolic health.

A key discovery in the research was the role of bile salt hydrolase (BSH), an enzyme that protects metabolic health, with engineered gut bacteria expressing the bsh gene improving body fat, insulin sensitivity, and glucose control in mice.

Engineered E. coli bacteria producing various BSH variants showed that only the variant mimicking Dubosiella newyorkensis, which exhibits a specific daily rhythm, led to significant metabolic improvements in the mice.

The focus on bile salt hydrolase (BSH) revealed that its activity increased during the daytime under a restricted eating schedule, emphasizing the enzyme's role in metabolic health.