The gut microbiome a complex community of bacteria and other microorganisms helps convert food into energy with many microbes following daily activity cycles. However high-fat diets can disrupt these rhythms and contribute to metabolic diseases.

The team then engineered the bsh gene into a harmless gut bacterium. Mice given this modified microbe showed lower body fat improved insulin sensitivity and better glucose control effectively mimicking the benefits of TRF. These findings may help advance new therapies for obesity diabetes and related metabolic disorders.

To investigate how TRF influences microbial function the researchers used metatranscriptomics a technique that measures real-time gene expression in gut bacteria. Since TRF alters the timing of food intake they hypothesized it would trigger time-dependent changes in microbial activity that traditional methods might miss. To test this they analyzed the gut microbiomes of three groups of mice: one on a high-fat diet with TRF another on the same diet with constant food access and a control group on a standard diet with unrestricted feeding. 

While the results indicate that TRF positively influences microbial function the researchers also ran additional experiments to determine whether specific microbial activities were directly driving the observed metabolic benefits.

The team focused on the transcription of BSH an enzyme known to break down fats during digestion and to influence glucose metabolism. Previous research in Zarrinpar’s lab suggested that BSH activity may contribute to metabolic improvements. In the current study TRF resulted in the expression of the bsh gene during the daytime in the gut bacteria Dubosiella newyorkensis which has a functional equivalent in humans.

With this knowledge in hand the researchers engineered a set of gut bacteria to express different versions of the bsh gene. These included variants from bacteria that were more active under high-fat feeding under normal conditions and under TRF. When tested in mice only the version from D. newyorkensis which was more highly expressed during TRF led to metabolic improvements.

Mice given these engineered bacteria had better blood sugar control lower insulin levels less body fat and more lean mass said Zarrinpar. This demonstrates how metatranscriptomics can help identify time-dependent microbial functions that may be directly responsible for improving host metabolism. It also shows the potential for designing targeted microbial therapies based on these functional insights.

Source: https://today.ucsd.edu/story/tracking-microbial-rhythms-reveals-new-target-for-treating-metabolic-diseases