The gut methanotroph Methylocystis intestini modulates intestinal peristalsis and fat metabolism via reducing methane levels

Methane, a predominant component of human intestinal gas, has been reported to be associated with a reduction in intestinal transit speed, as well as correlations with elevated body mass index. While the gut methanogenic archaea that produce this gas have been studied, the countervailing role of methane-consuming bacteria (methanotrophs) within the human gut ecosystem remains a critical, under-explored area. The potential for these bacteria to act as a built-in sink for intestinal methane and thereby mitigate its negative physiological effects is unknown. Here, we isolate an unreported methanotroph from human fecal samples, classified as Methylocystis intestini. Using a mouse model, we observe that methane challenge is associated with gastrointestinal motility and fat metabolism. We then demonstrate that the administration of Methylocystis intestini effectively reverses these dysfunctional processes, restoring motility and metabolic parameters. Additional analysis of methane-oxidation genes abundance in 1207 public metagenomic sequences from individuals with varying health statuses, including obesity and constipation, provides consistent correlative support for our experimental conclusions. Expanding this view to a global scale, we conducted a metagenomic survey of 550 human fecal samples from populations across five continents. This broader analysis reveals that methane-oxidizing genes are not a rarity but a common feature of the human gut microbiome, being detectable in over 91% of samples. This ubiquity underscores their fundamental role in human biology. Collectively, our findings establish gut methanotrophs as key mediators of intestinal methane level. Their presence is widespread across global populations, and their functional capacity can balance the effects of methane on host physiology. This work elucidates a crucial component of gut homeostasis and opens a promising avenue for developing microbiome-based therapeutic strategies aimed at managing methane-related gastrointestinal disorders by harnessing the power of these native methane-consuming bacteria.