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Obesity / Metabolic Disease · Journal article
Gut Microbes · July 15, 2026
Encouraging direction, but not yet definitive.
This multi-cohort analysis reveals reproducible compositional and ecological restructuring of the nonbacterial gut microbiome in obesity across three independent human cohorts. Individuals without obesity show enrichment of methanogenic archaea while those with obesity demonstrate increased bacteriophages, with significant reorganization of microbial network interactions at the species level.
Multi-cohort compositional analysis with covariate adjustment and network approaches. Individuals with and without obesity across three cohorts including an elderly cohort.
Individuals without obesity showed reproducible enrichment of methanogenic archaea, particularly Methanobrevibacter smithii and Methanobrevibacter millerae Individuals with obesity were characterized by increased abundance of bacteriophages from the class Caudoviricetes In an elderly cohort, eukaryotic taxa such as Blastocystis spp. were additionally associated with the without obesity group
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These findings expand understanding of obesity-associated microbiome dysbiosis beyond bacteria to include archaeal and viral components, potentially identifying new targets for metabolic health interventions. The reproducibility across cohorts strengthens the biological relevance of these nonbacterial signatures, though interventional studies are needed to establish causality.
Multi-cohort observational analysis identifies reproducible nonbacterial microbiome signatures in obesity with robust cross-cohort consistency, though causality remains unestablished.
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These findings expand understanding of obesity-associated microbiome dysbiosis beyond bacteria to include archaeal and viral components, potentially identifying new targets for metabolic health interventions. The reproducibility across cohorts strengthens the biological relevance of these nonbacterial signatures, though interventional studies are needed to establish causality.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Obesity is a complex metabolic disorder increasingly linked to alterations in the gut microbiome. While most research has focused on bacterial communities, the contribution of nonbacterial components including viruses, archaea, and eukaryotic microorganisms remains insufficiently characterized. Here, we performed a multicohort analysis to investigate the role of the nonbacterial gut microbiome in obesity across three independent human cohorts. Using compositional analyses adjusted for key covariates and network based approaches, we identified consistent multikingdom alterations associated with obesity. Individuals without obesity showed a reproducible enrichment of methanogenic archaea, particularly Methanobrevibacter smithii and Methanobrevibacter millerae, whereas individuals with obesity were characterized by increased abundance of bacteriophages from the class Caudoviricetes. In an elderly cohort, eukaryotic taxa such as Blastocystis spp. were additionally associated with the without obesity group. These patterns were largely consistent across cohorts and robust to sex stratification. Beyond taxonomic differences, ecological network analyses revealed substantial reorganization of microbial interactions in obesity. The identity and composition of hub taxa differed significantly between obesity and without obesity networks across all cohorts, indicating a shift in the taxa occupying central ecological roles. Notably, these differences were observed even when similar microbial kingdoms were represented, underscoring the importance of species-level resolution. Collectively, our findings demonstrate that obesity is associated with coordinated compositional and ecological alterations across the nonbacterial gut microbiome. This multikingdom perspective expands current understanding of microbiome dysbiosis in metabolic disease and highlights the archaeome and virome as potential contributors to host metabolic health.
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