Beyond the Gut: Unveiling Methane's Role in Broader Physiological Systems

Interest in the endogenous role of methane has grown rapidly over the past decade, driven both by its relevance for disease detection (including intestinal methanogen overgrowth) as well as discoveries that raise the possibility of endogenous sources of methane and suggestive evidence of methane effects relevant to physiology. This review explores both established and emerging origins of breath methane, its physiological relevance, and the evolving landscape of detection methods. We aim to summarize current understanding and provide a platform to outline key directions for future research. Evidence supports the existence of non-microbial, endogenous methane production pathways and potential biological effects beyond the gut. However, the concentrations generated via these pathways and the levels required to elicit physiological responses remain under investigation. Recent technological advances have enabled more accessible and longitudinal breath methane monitoring, opening new avenues for research and clinical application.