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Time-restricted feeding restored a healthy gut microbiome that was lost with diet-induced obesity in a mouse study.

The findings might help explain how time-restricted eating might prevent obesity and type 2 diabetes in people, Ana Carolina Dantas Machado, PhD, from University of California San Diego (UCSD), and colleagues suggest.

The team compared changes in the ileal microbiome (the microbe composition in part of the small intestine) every 4 hours during a 24-hour period in three groups of mice.

The mice had spent 8 weeks eating as much as they wanted of:

• A normal chow diet, 24 hours a day (control),

• A high-fat chow diet, oxycontin op 20 high 24 hours a day (diet-induced obesity), or

• A high-fat chow diet, 8 hours during the dark (the active period in mice; time-restricted feeding).

Time-restricted feeding restored diurnal rhythms of ileal microbiome oscillations, bile acid signaling, GLP-1 signaling (which affects glucose metabolism), and circadian rhythms of transcription of protein-coding genes that were lost in mice with diet-induced obesity.

Unlike other gut microbiome research, this study focused on the ileum rather than the large intestine or stool.  

In mice and humans, the ileum — the final stretch of the small intestine, which connects to the cecum, the first part of the large intestine — is important in metabolic health, according to a statement from UCSD.

Nutrients are drawn out of liquefied food in the ileum, and water is extracted from liquified food in the cecum.

“It’s important to realize that the gut microbiome is constantly changing, not only based on what we’re eating, but also based on the time of day,” stressed senior author Amir Zarrinpar, MD, PhD, assistant professor of medicine at UCSD School of Medicine and a gastroenterologist at UCSD Health.

Multiple Snapshots of the Gut Throughout the Day

“Most researchers are getting snapshots of this constantly shifting environment, which makes it hard to understand what is going on in the gut,” he said.

In the study, the team was “trying to get multiple snapshots throughout the day, almost like a movie, to better understand how food and the microbiome interact to affect weight gain and diabetes.”

The results show that “cyclical changes in the gut microbiome are quite important for health since they help with the circadian clock, and with that the regulation and control of glucose, cholesterol, and fatty acids — and overall metabolic health,” Zarrinpar summarized.

“It is interesting that restricting food access with [time-restricted feeding] acts not only through restoration of patterns affected under the unhealthy state, but also through new pathways,” said Machado, who is a postdoctoral student in Zarrinpar’s lab.

“These findings underscore the influence of diet and tim- restricted feeding patterns in maintaining a healthy gut microbiome, which in turn, modulates circadian rhythms that govern metabolic health,” stressed Zarrinpar.

“It’s a very complicated relationship between the microbiome and host,” he added, “with the former helping determine the latter’s gastrointestinal functioning and health.”

For future studies, researchers should keep in mind that “two investigators performing the same exact [microbiome] study in similar settings may come to different conclusions solely based on the timing of their sample collection,” the researchers note, and drugs may affect gut function differently depending on the state of the microbiome at a particular time or time of day.

The investigators are supported by grants from the National Institutes of Health. Zarrinpar and a study coauthor are co-founders and equity holders in Endure Biotherapeutics. Another study co-author is author of “The Circadian Code,“ for which he is paid royalties.

Cell Reports. Published online July 5, 2022. Full text

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