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Intestinal microbiota serves as a key mediator linking dietary signals to host homeostasis, while AI enables efficient integration of multi\u2010omics data to construct microbial metabolic models, identify interaction patterns across biological scales, and support prediction\u2010informed modulation of diet\u2010microbiota interactions. This paradigm synergizes dietary intervention design, AI technology, intestinal microbiota modulation, and host health enhancement, offering innovative solutions for chronic disease management, animal health breeding, and food safety monitoring. In this review, we summarize the core mechanisms of the four\u2010dimensional interaction and the application value of AI\u2010driven informed optimization. This review also discusses the major challenges currently facing the field, including model interpretability, multi\u2010source data heterogeneity, and cross\u2010species translation, and further highlights that future research should focus on establishing interpretable and iterative AI\u2010driven closed\u2010loop systems. This integrated approach holds immense potential to revolutionize host wellness research and promote the development of nutritional health and related industries. Unlike existing diet\u2010microbiota\u2010host frameworks and AI\u2010assisted precision nutrition approaches that mainly focus on association analysis or outcome prediction, our proposed paradigm positions AI as an active coordination layer linking dietary inputs, microbial responses, and host outcomes. By integrating mechanism\u2010informed modeling with iterative feedback, this framework enables dynamic optimization of diet\u2010microbiota interactions and supports more precise host health regulation.<\/jats:p>","DOI":"10.1002\/imo2.70133","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:52:26Z","timestamp":1787806346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Artificial intelligence driven diet\u2010intestinal microbiota\u2010host health integration: A four\u2010dimensional paradigm for advancing host wellness research"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-589X","authenticated-orcid":false,"given":"Tianle","family":"He","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Southwest University Chongqing China"},{"name":"Key Laboratory of Animal Nutrition and Bio\u2010feed Chongqing 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