Age-Related Dynamics of Methanogenic Archaea in the Human Gut Microbiome: Implications for Longevity and Health

Abstract

The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. To address these questions, we analyzed metagenomic data from the stool samples of young adults (n=127, Age: 19-59 y), older adults (n=86), and centenarians (n=34, age: 100-109 years). Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in Methanobrevibacter smithii, rather than Ca. M. intestini. Remarkably, Ca. M. intestini emerged as a central player in the network stability of adults, paving the way for M. smithii in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. Furthermore, the mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with butyrate-producing Oscillospiraceae. This study underscores the crucial role of the archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of Ca. M. intestini and the partnership between methanogens and specific butyrate-producing bacteria for enhanced health and potential longevity.

Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut

“…For detailed proteomic and metabolomic studies, this study focused on vesicles from Methanobrevibacter species, the most abundant archaea in the human gut microbiome, comprising up to 4% of the microbiome 86 . Methanobrevibacter species rely on syntrophic bacterial partners that provide small organic compounds like H 2 (or formate) and CO 2 for methanogenesis 63,87,88 . The bacterial partner benefits from this interaction, as potentially inhibiting end products of fermentation are efficiently removed 63,87,88 .…”

“…Methanobrevibacter species rely on syntrophic bacterial partners that provide small organic compounds like H 2 (or formate) and CO 2 for methanogenesis 63,87,88 . The bacterial partner benefits from this interaction, as potentially inhibiting end products of fermentation are efficiently removed 63,87,88 . As such, a well-regulated and controlled interaction with bacterial syntrophic partners is highly crucial for Methanobrevibacter species.…”

Expanding the cultivated human archaeome by targeted isolation of novelMethanobrevibacterstrains from fecal samples

“…Draft metabolic models were generated using gapseq (v1.2) (34) on the genomes of the B. thetaiotamicron , C. minuta and M. smithii (GenBank IDs NC_004663.1, GCF_001652705.1 and ABYW00000000.1, respectively). The recipes for MS and MpT1 media were used to build a representation of media constituents in the ModelSEED (35) namespace.…”