by Katharine Harris, PhD
Postdoctoral fellow in the Department of Medicine
Section of Gastroenterology, Hepatology & Nutrition
Katya Frazier, a second-year graduate student at the University of Chicago, arrived home at 3 a.m. again. It took her three minutes to jog from the lab back to her apartment; living close to work is a big perk when you are collecting microbial samples from mice at 2 a.m. Katya wants to know what microbes are doing in the middle of the night, and so she routinely gives up sleep to collect samples.
For years, scientists have observed that our bodies function differently throughout the course of a day. Body temperatures, hormone levels, immune function, and metabolism all exhibit daily rhythms, oscillating over the course of 24 hours. In fact, this year’s Nobel Prize in Physiology or Medicine was awarded to researchers for their discovery of the biological underpinnings of this circadian clock, now known as a powerful influence in maintaining health.
Researchers at the University of Chicago are investigating how the vast community of microbes that live in and on the human body participate in this daily dance, and Katya is an important member of this team. In 2015 Vanessa Leone, PhD, and Eugene Chang, MD, published some breakthrough research on the circadian rhythms of the microbial community in the gut using mice as their model system. Their work showed that the abundance and function of microbial species living in the guts of mice differs depending on the time of day and that these fluctuations influence whether or not the mice became obese.
How does this happen? The major biological clocks in our body are set by light/dark cues. But the microbes that live in the gastrointestinal tract never see the sun, so how could they know the time of day? One part of the answer is the diet of their host. What, when, and how much the mice eat directly affects what nutrition is available to their microbes.
Leone and Chang’s 2015 experiments fed one set of mice a regular, low-fat, high-fiber mouse chow and another set a high-fat diet. Perhaps not too surprisingly, the mice on the high-fat diet gained much more weight.
When the team examined both the mouse fecal matter and contents of their digestive systems, they found starkly different microbial composition between the two groups. Surprisingly, in the mice fed the low-fat diet, the types of bacteria changed in abundance and function over the course of 24 hours, and so did the waste products they put out, with levels rising and falling depending on the time of day. In the mice on the high-fat diet, the bacterial balance varied much less, as did their waste products, sending a steady stream out to the liver, one of the main organs involved in metabolizing fat.
Perhaps the microbes on the high-fat diet lost track of time and confused the rhythm of the liver? Or was it the liver that was somehow telling the microbes what time it was? And how do the oscillations in microbial populations influence metabolic diseases, such as obesity and type 2 diabetes? These are the questions that Katya and Dr. Leone’s team are seeking to answer.
Modern life—with its electric lights, shift work, constantly available food, and quick and easy international travel—assault our biological rhythmicity, the sleep/wake cycles developed over eons of evolution. Circadian disruptions are associated with higher rates of metabolic disorders, increased blood pressure, high blood sugar, abnormal cholesterol levels, obesity, and elevated risk for heart disease, stroke, diabetes, and even some cancers. Maybe understanding and being able to manipulate the 24-hour variations of our microbial tenants can help prevent some of these outcomes.
And so Katya continues to visit the lab at all hours of the day and night, observing how microbial populations are expanding and contracting, digesting their host’s food and spitting out waste products, in an effort to communicate with the host that provides their habitat. Each time Katya’s alarm sounds in the middle of the night and she flips on the lights, perhaps her own microbes are startled out of rhythm in reaction to their host’s strange and unexpected behavior, altering their own behavior in response.
Katya says she knew what she was signing up for when she chose this research, but she finds working on such a fascinating problem worth the stress on her own circadian rhythms. Her hope is that studying these mice and their bacteria carefully may provide powerful knowledge that will help us restore and maintain circadian rhythms and promote wellness.