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November 14, 2016 | 4 minute read

High-fat Diet Disrupts Gut Microbe’s Circadian Clock in Mice, May Impact Obesity Risk

WASHINGTON, DC — Laboratory research presented today at the American Institute for Cancer Research (AICR) Research Conference reveals that the trillions of bacteria in our gut exhibit their own circadian behavior, the day versus night variation that manages everything from our own appetite to metabolism.

A high-fat, low-fiber diet disrupts those circadian cycles in both the mice and the bacteria, leading to changes in the daily rhythms that can impact metabolism and obesity risk.

Prior research shows that gut microbes are important to good health and may play a role in obesity. Gut microbes, for example, digest fiber to produce short chain fatty acids (SCFAs) that affect appetite regulation, obesity and colon health. The SCFA butyrate, for example, is studied for its role in lowering colon cancer risk. Yet little research has delved into whether gut microbes exhibit circadian rhythm activity, and how that may affect health.

“One of the interesting things this work has shown is that changes in the diet induce changes in day versus night activity of the gut microbes,” said the study’s lead author Vanessa Leone, PhD, at the University of Chicago. “If you feed a mouse a high-fat, Western-style diet you get a change in the gut’s microbial community as well as disrupt the microbial circadian rhythms.”

Changes in Animal’s Microbes, Circadian Patterns

In the study, one group of mice consumed a high-fat, low-fiber diet while another group was fed a standard low-fat, high-fiber diet. All the animals had full exposure to the food both day and night. After five weeks the high-fat consuming mice gained 20% of their body weight. They also had a significant reduction in gut microbial diversity, and the percent of microbes that showed day versus night patterns was reduced from approximately 15 percent to only 5 percent.

“We saw that the mice on the high-fat diet were losing a lot of gut microbes that would produce short chain fatty acids and other metabolites that are considered good for us,” said Leone. “We also saw a reduction in the absolute number of bacteria and there wasn’t much of a change in gut microbes between day versus night – everything stayed pretty much stagnant.”

“In the low-fat, high-fiber group there was a day versus night pattern to microbial activity, high at one point during the day then low, and that repeats itself every 24 hours. In the mice fed the high-fat diet, the microbes lose that pattern, they also have lower levels of activity all together.”

Specific metabolites produced by gut microbes, including butyrate, directly changed circadian clock genes in the liver, “the grand central station in terms of handling metabolites,” said Leone. The altered gene expression seen in the high-fat conditions shifted the animals to a lower metabolic state and possibly, diet-induced obesity.

This is a budding area of research, says Leone, and there is a lot to be discovered. “But if we could understand how what you eat changes the way gut microbes regulate the liver’s circadian clock that could lead to more personalized strategies to treat and prevent obesity.”

Microbes and Cancer

The study was published in the journal Cell Host & Microbe.

In addition to these studies, other research on microbes and cancer to be presented at the AICR Research Conference include:

  • Findings of a pilot study on exercise and the gut that suggests greater gut microbial diversity among participants who reported being the most physically active compared to the most inactive.
  • The impact of black raspberry feeding on the colon’s microbiome and phytochemical metabolites in mice


  • Leone V, Gibbons SM, Martinez K, et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe. 2015;17(5):681-689

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