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Dec 17, 2025
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Abstract

The human gastrointestinal tract harbors a diverse and dynamic microbiome, comprising trillions of bacteria, viruses, fungi, and archaea that interact intricately with the host immune system. This bidirectional crosstalk is central to the maintenance of homeostasis and the prevention of chronic diseases. Over the past decade, advances in metagenomics, metabolomics, and immunology have unraveled the profound influence of gut microbiota-derived signals on both mucosal and systemic immunity. Short-chain fatty acids, microbial metabolites, and structural components such as lipopolysaccharides and peptidoglycans act as key mediators that calibrate the immune tone, influencing innate and adaptive responses. Dysbiosis, or disruption in microbial balance, has been implicated in inflammatory bowel disease, autoimmune disorders, metabolic syndromes, neuroinflammatory conditions, and cancer immunotherapy outcomes. This review provides a comprehensive analysis of the microbiome–immune crosstalk, tracing its molecular and cellular pathways, delineating its systemic reach beyond the gut, and highlighting its therapeutic potential. We explore recent findings on microbial modulation of T cells, dendritic cells, and macrophages, the role of microbial metabolites in epigenetic programming, and the emerging field of microbiota-targeted therapeutics. The manuscript concludes with future perspectives on precision microbiome engineering for immune modulation and translational challenges in clinical application.

Keywords

Microbiome; Gut–immune axis; Systemic immunity; Dysbiosis; Short-chain fatty acids; Immunomodulation.

Article Details

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