Methane-producing Bacteria in Gut May Increase Risk for Diabetes

With the diabetes epidemic growing into a global health crisis, it is critical to understand the factors that put people at risk for developing diabetes. While obesity is known to be a significant contributor, scientists are still plagued with identifying additional factors that make some individuals more susceptible to developing diabetes than others. In a recent study, ADA-funded investigator Ruchi Mathur, MD, from Cedars-Sinai Medical Center, began exploring a possible link between microorganisms found in the gut and an increased risk of developing obesity and diabetes.

In earlier studies, Dr. Mathur had found that flourishing populations of methane-producing microbes in the digestive tract can directly contribute to weight gain. Methane slows movement through the intestines, allowing a greater amount of time for the body to absorb nutrients and extract calories from food. The bacterial species Methanobrevibacter smithii (M. smithii) is responsible for the majority of methane production in the human body, and Dr. Mathur observed that people with high intestinal concentrations of these bacteria tend to have a higher body mass index (BMI), more body fat, and elevated blood-sugar levels. These individuals also extracted a greater number of calories from the same quantity of food than those with lower levels of M. smithii, leading to considerable weight gain over time.

Dr. Mathur believes that her findings may explain why some people experience difficulty with losing weight even with a healthy diet and exercise. "Usually, the microorganisms living in the digestive tract benefit us by helping convert food into energy. However, when this particular organism – M. smithii – becomes overabundant, it may alter this balance in a way that causes someone to be more likely to gain weight," she said.

Dr. Mathur is now using her American Diabetes Association Innovation Award to take a closer look at how people digest food differently in the presence or absence of M. smithii. She is currently recruiting study participants who are obese or have prediabetes, and that have high methane gas content in their breath (which can be measured as they exhale using a simple breath profile test). In the study, the subjects will be given a standard three-day diet and will also swallow a SmartPill that records information on gut motility and transit time as it passes through the gastrointestinal tract. The participants will then repeat the same set of tests after M. smithii is eliminated from their digestive tract with a targeted antibiotic.

In addition to motility and calorie analyses, the laboratory team will measure changes in the subject's body fat distribution, hormone levels, responses to insulin, and other factors. By comparing data before and after antibiotic treatment, the impact of the methane-producing bacteria in the gut can be determined. To date, the investigator has nearly completed study recruitment and expects to perform the laboratory and data analyses within the next few months.

"This should let us know just how energy balance is affected by M. smithii. We're only beginning to understand the incredibly complex communities that live inside of us. If we can understand how they affect our metabolism, we may be able to work with these microscopic communities to positively impact our health," said Dr. Mathur.

If the clinical trial definitively demonstrates that methane producing bacteria contribute significantly to weight gain and insulin resistance, the research team could start developing more refined treatment approaches to reduce methane production and improve glucose metabolism in people with obesity, prediabetes, and diabetes. With roughly 30 million Americans already with diabetes and another 86 million with prediabetes, the investigator hopes that modulating people's gut microbial communities may delay or prevent the development of diabetes.