Abstract:
The human gut serves as home to trillions of microorganisms, forming a complex and dynamic ecosystem that influences nearly every aspect of human health. While much of the research so far has focused on bacteria, the gut also harbours another fascinating but less explored group of microbes—archaea. Among them, methanogens stand out for their ability to produce methane gas in the gut, a function that may play important roles in digestion, microbial balance, and overall gut physiology. Unlike the bacterial microbiome, which has been studied extensively and is known to vary widely across individuals depending on geography, diet, lifestyle, medication, environment, and genetics, the gut archaeome remains comparatively underexplored. Its diversity, distribution, and functional contributions to human health are still poorly understood. In particular, how archaeal populations change across different conditions and how they interact with bacterial communities are key questions that remain unanswered. To address this gap, we conducted a large-scale analysis of 55,788 human gut metagenomes, focusing specifically on the distribution and ecological associations of methanogens. Using relative abundance data from 7,471 gut microbiomes, we found that methanogen prevalence is far from uniform; instead, it displays distinct patterns strongly shaped by geography, lifestyle, and host-associated factors. Interestingly, certain populations showed markedly higher carriage rates of methanogens, suggesting that environmental exposures, dietary practices, and cultural traditions may play a crucial role in shaping archaeal communities. Our analysis further revealed important host-related associations. When examining body mass index (BMI), we observed a negative correlation between methanogen prevalence and BMI. Methanogen levels were highest in underweight individuals and progressively decreased toward obese individuals. Among species, Methanobrevibacter smithii emerged as the most dominant archaeon, though prevalence patterns varied notably between males and females. We also explored the potential links between methanogens and human disease. Our findings suggest that methanogen presence is not random but may be closely tied to health outcomes. For example, M. smithii has been implicated in conditions such as Parkinson’s disease and intestinal polyps, while also showing positive associations with gut-related disorders, type 2 diabetes, and other metabolic conditions. These associations hint at a possible role of methanogens in either contributing to or modulating disease pathways, though the exact mechanisms remain to be clarified. Finally, through co-occurrence network analysis, we observed that methanogens tend to cluster with specific bacterial communities. This points to potential ecological interactions and niche specialization within the gut ecosystem, where methanogens may work in tandem with or compete against other microbes, thereby influencing broader microbiome structure and function. Together, these findings underscore the importance of moving beyond bacteria-focused studies and paying closer attention to the archaeome. Methanogens, long overlooked in human microbiome research, may hold critical clues about how microbial ecosystems function, how they interact with host factors, and how they influence health and disease. A deeper exploration of their ecological and functional roles could open new avenues for microbiome-based diagnostics and therapeutics.