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Despite rapid advances, major gaps remain between predicting metabolic complementarity, demonstrating causal donor\u2013resource\u2013recipient transfer, establishing ecological robustness, and achieving therapeutic benefit. Here, we organize current evidence within a Mechanism\u2013Technology\u2013Application framework. We summarize four representative and non\u2010exclusive resource\u2010transfer scenarios: sequential resource transformation, diffusible metabolite coupling, micronutrient exchange or capture, and transfer of amino acids and other nitrogenous compounds, together with host\u2010associated metabolic axes and noncanonical release routes. We then distinguish the evidentiary roles of multi\u2010omics and metabolic modeling, culture\u2010based perturbation, stable\u2010isotope tracing, synthetic communities, and host\u2010associated models. Finally, we evaluate how dietary substrates, multi\u2010strain live biotherapeutic products, and engineered strains may reshape microbial resource flows, while emphasizing that metabolic compatibility, engraftment, and host\u2010active metabolite production do not by themselves establish cross\u2010feeding or clinical efficacy. Cross\u2010feeding\u2010informed intervention therefore remains an emerging, mechanism\u2010driven strategy rather than a validated engineering platform. Progress will require prospective validation of the causal chain linking resource availability, metabolite transfer, ecological persistence, product stability and safety, and clinically meaningful outcomes across heterogeneous human hosts.<\/jats:p>","DOI":"10.1002\/advs.77267","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:35:43Z","timestamp":1787135743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Programming Gut Microbiome Function Through Cross\u2010Feeding: From Ecological Mechanisms to Live Biotherapeutics"],"prefix":"10.1002","volume":"13","author":[{"given":"Chuankai","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Dairy Biotechnology and Engineering Ministry of Education Inner Mongolia Agricultural University  Hohhot People's Republic of China"},{"name":"Key Laboratory of Dairy Products Processing Ministry of Agriculture and Rural 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