On the seventh episode of The Microbiome Podcast we had a great conversation with Drs. Eugene Chang and Vanessa Leone from the University of Chicago. Drs. Chang and Leone found that bacteria in the gut influence the circadian clock in mice. They discovered that altering the diet of the mouse by introducing a high-fat diet caused conventionally raised mice to have a disrupted circadian clock and became obese. They looked at what genes were expressed in the liver and found that the genes expressed varied widely from mice that were germ-free and those that were normal and conventionally raised. We talked with them about this work and what influence this could have on humans and on our eating and sleeping patterns.

Listen to the podcast here on our website, here on iTunes, and here on Stitcher.

Below are more detailed show notes:

Two scientific talks that David saw in New York City. First (0:37), a talk by AMI Scientific Advisory Board member Marty Blaser about antibiotics and obesity. We then (1:23) discussed a talk by Chris Mason about the microbiome and his study on the microbes in the NYC transit system. Dr. Mason published his slides on twitter so if you’re interested in seeing his slides, you can see them here.
(2:26) Dr. Tim Spector from Kings College London had his son eat only McDonalds for 10 days straight. His son lost approximately 40% of the bacterial diversity in his gut. Read more about it here.
(3:40) The British Gut Project that Dr. Tim Spector leads, a partner of The American Gut Project. Check out the British Gut Project.
(5:37) A company called Biomecite Diagnostics that licensed technology from The University of Maryland School of Medicine to develop molecular diagnostics to detect inflammatory bowel diseases like Crohn's disease and ulcerative colitis. Read more here.
(6:10) We gave an overview of diurnal changes, circadian clock, and the microbiome.
(9:21) We began the interview with Drs. Chang and Vanessa Leone and discussed their paper that found that cirdcadian clocks were influenced by gut microbes. Read the paper in Cell Host and Microbe. Read our blog post about this work.
(11:47) Dr. Leone discussed a few seminal papers from 2014 about diurnal changes. Read this paper about jet-lag and the microbiome.
(34:15) After the interview with Drs. Chang and Leone we talked about our own sleep patterns.
(37:18) We gave our own opinions on Deflategate and Bill goes on a little rant about the Patriots, Tom Brady, and deflated footballs.

Our bodies’ internal circadian clock may be profoundly important to our health, especially as it pertains to our metabolism. Research has shown that people who have altered sleep cycles, like those who work the night shift, are at an increased risk for diabetes, obesity, and metabolic syndrome. Researchers from the University of Chicago recently investigated how the microbiome may be involved in the complex relationship between disruptions to circadian rhythms and obesity. They published their results in the journal Cell Host & Microbe.

The human circadian clock is regulated by a few organs in our bodies, including the brain, the liver, and is now evident from this study, the microbiome. The researchers first measured gene regulation by the liver in germ free mice and normal mice. They discovered that many of the genes that had daily rhythmic variations had their rhythms greatly affected by the presence and absence of bacteria in the gut. They then subjected these mice to high fat and low fat diets and learned that, unsurprisingly, the high fat diet led to obesity in normal mice. Surprisingly though, the high fat diet did not lead to obesity in germ-free mice. Interestingly, many of the liver genes that were expressed rhythmically by the gut also had their rhythms affected by diet, with different genes having their expression altered depending on the diet.

The researchers then discovered that the populations of bacteria that comprise the microbiome also exhibited rhythmic variations throughout the day. These variations did not necessarily relate to time of feeding either, as mice that were fed constantly throughout the day still experienced these variations. Moreover, they realized that specific metabolic functions also changed rhythmically throughout the day, such as utilization of specific carbohydrates, and that a high fat diet would quell these rhythms.

The scientists then measured certain metabolites produced by the microbiome, such as short chained fatty acids (SCFAs), and saw these were also produced rhythmically throughout the day, which may be, but is not entirely, related to the differences in microbiome populations. Metabolites rhythms were also affected by diet. For example the high fat diet decreased SCFA rhythms. The scientists then determined that these metabolites have a direct impact on the cycling of liver circadian genes. This means that the microbiome metabolites and the human liver combine to contribute to our circadian clock.

The researchers go on to hypothesize that consuming a high fat diet disrupts our natural circadian rhythms, which leads to a lower metabolic state and results in obesity. This hypothesis extends to the germ free mice which did not become obese regardless of diet; that is, they did not have a disrupted microbiome to alter their rhythms. Ultimately, the healthiest and strongest circadian rhythms belonged to the normal mice eating normal food.

We have written before about how jet lag can lead to microbiome changes that cause obesity. This paper, in addition to the one described above show how our natural clock and the microbiome’s natural clock work in conjunction to regulate our metabolism. Our circadian rhythms are not something which many people associate with the microbiome, but over time complex systems like this evolve. While this paper may not make someone change his or her behavior, it may make him or her think twice before pulling an all-nighter or having that midnight snack.

Episode 7 of The Microbiome Podcast: Gut bacteria and circadian clocks with Drs. Eugene Chang and Vanessa Leone

When you eat and what you eat may lead to obesity