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This narrative review synthesizes recent advances in AI-driven gut microbiome research, focusing on machine learning, deep learning, transformer models, graph neural networks, and generative AI. It examines how AI facilitates the identification of diagnostic microbial signatures, prediction of therapeutic responses, and design of personalized interventions. The review highlights the use of AI-driven multi-omics integration to improve functional interpretation of host-microbiome interactions, citing examples such as personalized nutrition models achieving AUC > 0.8 for predicting glycemic responses and accurate forecasting of short-chain fatty acid production.
AI's ability to predict individual responses to microbiome-targeted therapies and design personalized nutritional interventions is rapidly accelerating, achieving AUCs over 0.8 in predicting postprandial glycemic responses.
Background: The rapid advancement in artificial intelligence (AI) has fundamentally reshaped gut microbiome research by enabling high-resolution analysis of complex, high-dimensional microbial communities and their functional interactions with the human host. Objective: This narrative review aims to synthesize recent methodological advances in AI-driven gut microbiome research and to evaluate their translational relevance for therapeutic optimization, personalized nutrition, and precision medicine. Methods: A narrative literature review was conducted using PubMed, Google Scholar, Web of Science, and IEEE Xplore, focusing on peer-reviewed studies published between approximately 2015 and early 2025. Representative articles were selected based on relevance to AI methodologies applied to gut microbiome analysis, including machine learning, deep learning, transformer-based models, graph neural networks, generative AI, and multi-omics integration frameworks. Additional seminal studies were identified through manual screening of reference lists. Results: The reviewed literature demonstrates that AI enables robust identification of diagnostic microbial signatures, prediction of individual responses to microbiome-targeted therapies, and design of personalized nutritional and pharmacological interventions using in silico simulations and digital twin models. AI-driven multi-omics integration—encompassing metagenomics, metatranscriptomics, metabolomics, proteomics, and clinical data—has improved functional interpretation of host–microbiome interactions and enhanced predictive performance across diverse disease contexts. For example, AI-guided personalized nutrition models have achieved AUC exceeding 0.8 for predicting postprandial glycemic responses, while community-scale metabolic modeling frameworks have accurately forecast individualized short-chain fatty acid production. Conclusions: Despite substantial progress, key challenges remain, including data heterogeneity, limited model interpretability, population bias, and barriers to clinical deployment. Future research should prioritize standardized data pipelines, explainable and privacy-preserving AI frameworks, and broader population representation. Collectively, these advances position AI as a cornerstone technology for translating gut microbiome data into actionable insights for diagnostics, therapeutics, and precision nutrition.