The daily clock of gut bacteria may have the key to fighting obesity

Scientists have found that a timed meal within the window for eight hours a day can not only help people lose weight—in fact, it resets the daily rhythm of gut bacteria in a new treatment that can lead to obesity and diabetes.

The findings suggest that when we eat, it may be as important as the food we eat for metabolic health.

UC San Diego researchers used a cutting-edge technology called Metatransscriptomics to peek into the gut microbiome and watch the bacteria work in real time. The challenge they found was how we view diet and metabolism.

Beyond bacteria

Most of the research focuses on which bacteria are used in our gut, but this study looks at what these bacteria actually do throughout the day. The team studied mice fed high-fat diets under different feeding schedules and found something compelling: the time-limited feeding part restored the natural rhythm of bacterial activity that would normally disrupt the high-fat diets.

“By looking at the RNA, we were able to capture dynamic changes in these microorganisms, and we couldn’t see the metagenomics of the changes,” said Stephany Flores Ramos, the first author of the study.

It can be considered as the difference between conducting a census throughout the day and watching modes of transportation. The census tells you who lives there, but traffic data reveals when and how people actually move around.

A unique enzyme

The researchers zeroed out a specific enzyme called bile saline hydrolase (BSH), produced by bacteria with the tongue stirring name Dubosiella Newyorkensis. This enzyme helps break down fat during digestion, but what sets it apart is the timing – it only becomes more active during the day when mice follow a restricted diet schedule.

To test whether the enzyme is actually responsible for the health benefits, the team did something clever. They designed harmless E. coli bacteria to produce different versions of BSH enzymes, including specific variants from D. newyorkensis, showing a unique daily rhythm.

The results are surprising. Only mice given engineered bacteria with time-sensitive enzyme variants can show improvements in metabolism.

Real-world impact

“Given the better blood sugar control of these engineered bacteria, mice with lower insulin levels, less body fat and higher quality,” said senior author Amir Zarrinpar. “This demonstrates how meta-word grouping helps identify time-dependent microbial functions that may be directly responsible for improving host metabolism.”

What’s particularly interesting is that D. Newyorkensis has the same function in humans, suggesting that these findings can be translated into human health. The study also shows that engineered bacteria show significant differences in their fat-treatment activities, highlighting how even similar enzymes have very different effects on metabolism.

A key discovery at a glance:

• Daily rhythm of bacteria that restrict feeding recovery when high-fat diet is interrupted
• Specific enzyme variants show time-dependent activity patterns
• Engineering bacteria mimic the metabolic benefits of restricted diet schedules
• Different enzyme versions have unique fat handling capabilities

expect

Will future treatments for obesity involve precise timing dose-engineering bacteria rather than restrictive diets? Researchers have planned to perform the next phase of testing in obese and diabetic mice.

“We also plan to explore other time-sensitive microbial genes found in our data to develop other engineered bacteria that can improve metabolic health,” Zarrinpar added.

The study, published in cell hosts and microorganisms, opens a new field of personalized medicine that can tailor treatments not only to individual patients but also to their daily schedules of bacteria.

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