Methane-producing human subjects have higher serum glucose levels during oral glucose challenge than non-methane producers: a pilot study of the effects of enteric methanogens on glycemic regulation

Background: Recent studies support that intestinal microbes contribute to human disease, and enteric methanogens have been specifically linked to altered gut metabolism and weight gain. In this study, we tested whether methane on breath test (as a surrogate for colonization with the predominant methanogen Methanobrevibacter smithii) is associated with altered glucose tolerance in humans. Methods: Consecutive methane producing (methane ≥3ppm, N=5) and non-methane producing (methane <3ppm, N=15) subjects undergoing lactulose breath test at our center were recruited and subjected to a 75 g oral glucose tolerance test (OGTT). Results: The average age of methane-producing subjects was 48.8±10.0 vs. 37.7±12.1 for non-methane subjects (P=0.17). Methane and non-methane subjects also had comparable mean body mass index (BMI) (23.9±0.2 vs. 25.0±8.0 kg/m2; P=0.53) and baseline insulin resistance (HOMA-IR) (1.32±0.72 vs. 2.21±1.52; P=0.23). During 180 minutes post-glucose load, methane producers had greater serum glucose area-under-the-curve (AUC) (774.2±140.3 mg/dL) than non-methane subjects (585.5±128.3 mg/dL) (P=0.03), but similar insulin AUC (217.76±122.08 μU/mL vs. 215.37±75.02 μU/mL, respectively). Conclusions: Individuals with methane on breath test (reflecting higher colonization with enteric methanogens, predominantly M. smithii) may have impaired glucose tolerance when challenged with a high carbohydrate load, and may also have a higher susceptibility to hyperglycemia which appears to be independent of basal insulin resistance and BMI.