Complete genome-derived metabolic interactions reveal the impact of gut ecology on human health
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.
Authors
- Xing Rao
- Wangsheng Li
- Chuanyu Liu (ORCID: https://orcid.org/0000-0003-2258-0897)
- Y. Wang (ORCID: https://orcid.org/0000-0002-0271-626X)
- Liye Yang (ORCID: https://orcid.org/0000-0002-5958-6785)
- Yu Tian (ORCID: https://orcid.org/0000-0002-6791-8217)
- Yuzheng Gu
- Jinlong Yang (ORCID: https://orcid.org/0000-0002-7358-3396)
- Xin Tong (ORCID: https://orcid.org/0000-0002-4849-6522)
- Hewei Liang (ORCID: https://orcid.org/0000-0003-4639-6314)
- Yiyi Zhong
- Hao Wang (ORCID: https://orcid.org/0000-0001-6881-9977)
- Jiayi Xu (ORCID: https://orcid.org/0000-0003-3465-7927)
- Jinhong Wang (ORCID: https://orcid.org/0000-0002-7552-5771)
- Mengmeng Wang (ORCID: https://orcid.org/0009-0009-5938-8939)
- Zhinan Wu
- Yuliang Dong
- Tao Zeng
- Yuning Zhang
- Yusheng Xu
- Haifeng Zhang
- Feng Zhao
- Yinglei Miao
- Liang Xiao
- Karsten Kristiansen
- Yangfeng Wen
- Yuanqiang Zou
- Bo Wang
- Juan Yang
- Peng Gao
- Xiaofan Sun
- Xun Xu
- Fushu Liu
- Zejun Yang
- Wenxin He
- Juan Zhao
- Xin Jin
- Yang Sun
Institutions
- BGI Group (China) (CN)
- University of Copenhagen (DK)
- Shanxi Medical University (CN)
- TCL (China) (CN)
- Kunming Medical University (CN)
- Northwest University (CN)
- First Affiliated Hospital of Kunming Medical University (CN)
- First Hospital of Shanxi Medical University (CN)
- Northwest Institute of Mechanical and Electrical Engineering (CN)
- Puer University (CN)
- MD Precision (Canada) (CA)
- University of Chinese Academy of Sciences (CN)
- BGI Research (CN)
- Northeast Forestry University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1016/j.celrep.2026.117913
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 3.03
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China