Metabolic interactions govern gut microbiome assembly, yet their functional rules remain obscured by genomic incompleteness and fragmentation. Here, we leverage 1,150 complete genomes to construct genome-scale metabolic models, demonstrating that draft assemblies introduce systematic artifacts and omit critical transport functions. We observe that genomic traits and niche specialization, rather than random association, shape microbial metabolic competition and complementarity. Interaction asymmetry stratifies strains into four ecological groups, including active players, resource predators, resource utilizers, and resource contributors, with distinct signatures of metabolite exchange, competition, and secondary metabolism. In inflammatory bowel disease, these groups show subtype-specific temporal instability, and group-specific dysbiosis predicts clinical phenotypes better than the whole-community profiles. Keystone features derived from integrated metabolic interaction and co-occurrence networks also improve cross-validated disease classification. Together, these findings connect genome completeness with microbial ecological organization and provide a framework for linking metabolic interactions to microbiome-associated disease.
Yu-He Gu, Haoyu Wang, Jin-Long Yang et al.· Cell Reports· 0 citations
High-throughput single-cell omics of non-human primate brain tissue provides a powerful platform to investigate the molecular basis of brain aging. Here, we present a comprehensive transcriptomic and chromatin accessibility atlas of 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques spanning the adult lifespan, including exceptionally old individuals. Our analyses reveal dynamic, cell-subtype- and region-specific age-related changes in core brain functions, including synaptic communication and axon myelination. We identify multicellular networks in the pons and medulla as a previously unrecognized hotspot of primate brain aging, highlighting white matter vulnerability as a central feature of aging. Integration with human brain aging and neurodegeneration datasets reveals both shared and divergent molecular mechanisms. We further define transcription factors and age-related chromatin remodeling programs linked to longevity and neurodegeneration. This spatiotemporal atlas establishes a foundational framework for understanding the cellular and regulatory architecture of primate brain aging and its links to disease.