Exhaled Methane Is Associated with a Lower Heart Rate

Background: In humans, methane (CH₄) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH₄ in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH₄ production. Recent reports have shown an association between CH₄ and vagal dysfunction as well as the inhibition of CH₄ activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings, we hypothesized that CH₄ may be affecting resting heart rate (HR) based on the potential effect of CH₄ on the vagus nerve. Objectives: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH₄ and resting HR in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association with breath CH₄ over time. Methods: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH₄. Second, we performed a post hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH₄ versus those that had a decrease in breath CH₄ over 14 weeks. Last, we assessed whether a larger decrease in CH₄ is associated with a larger increase in HR over time. Results: In the retrospective cohort, subjects with detectable CH₄ had a lower HR compared to those with undetectable CH₄ (73.0 ± 0.83 vs. 76.0 ± 0.44 beats/min, p = 0.01). In the post hoc analysis, a decrease in CH₄ over time was associated with an increase in HR (median ∆ = 6.5 ± 8.32 beats/min, p = 0.0006). Last, we demonstrated a biological gradient whereby a larger drop in CH₄ was associated with a greater increase in HR (R = −0.31, p = 0.03). Conclusion: Our findings suggest a potential role for the microbiome (and specifically CH₄ from methanogens) to regulate HR. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.