Ghosh N, Sinha K. Guardians within: Cross-talk between the gut microbiome and host immune system. World J Gastrointest Pathophysiol 2025; 16(4): 111245 [PMID: 41479870 DOI: 10.4291/wjgp.v16.i4.111245]
Corresponding Author of This Article
Nabanita Ghosh, PhD, Department of Zoology, Maulana Azad College, No. 8 Rafi Ahmed Kidwai Road, Kolkata 700013, India. nabanitaghosh89@gmail.com
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Gastroenterology & Hepatology
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Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 22, 2025 (publication date) through Jan 12, 2026
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Publication Name
World Journal of Gastrointestinal Pathophysiology
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2150-5330
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Ghosh N, Sinha K. Guardians within: Cross-talk between the gut microbiome and host immune system. World J Gastrointest Pathophysiol 2025; 16(4): 111245 [PMID: 41479870 DOI: 10.4291/wjgp.v16.i4.111245]
World J Gastrointest Pathophysiol. Dec 22, 2025; 16(4): 111245 Published online Dec 22, 2025. doi: 10.4291/wjgp.v16.i4.111245
Guardians within: Cross-talk between the gut microbiome and host immune system
Nabanita Ghosh, Krishnendu Sinha
Nabanita Ghosh, Department of Zoology, Maulana Azad College, Kolkata 700013, India
Krishnendu Sinha, Department of Zoology, Jhargram Raj College, Jhargram 721507, India
Author contributions: Ghosh N was responsible for conceptualization, literature review and data curation, writing original draft, supervision and project administration; Sinha K was responsible for table and figure design and writing review and editing; all of the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: No conflict-of-interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nabanita Ghosh, PhD, Department of Zoology, Maulana Azad College, No. 8 Rafi Ahmed Kidwai Road, Kolkata 700013, India. nabanitaghosh89@gmail.com
Received: June 26, 2025 Revised: July 28, 2025 Accepted: October 27, 2025 Published online: December 22, 2025 Processing time: 179 Days and 16.8 Hours
Abstract
The gut microbiome, a complex ecosystem of trillions of microorganisms, plays a crucial role in immune system regulation and overall health. This review explores the intricate cross-talk between the gut microbiota and the host immune system, emphasizing how microbial communities shape immune cell differentiation, modulate inflammatory responses, and contribute to immune homeostasis. Key interactions between innate and adaptive immune cells – including macrophages, dendritic cells, natural killer cells, innate Lymphoid cells, T cells, and B cells – and gut microbiota-derived metabolites such as short-chain fatty acids are discussed. The role of commensal bacteria in neonatal immune system development, mucosal barrier integrity, and systemic immunity is highlighted, along with implications for autoimmune diseases, inflammatory conditions, and cancer immunotherapy. Recent advances in metagenomics, metabolomics, and single-cell sequencing have provided deeper insights into the microbiota-immune axis, opening new avenues for microbiome-based therapeutic strategies. Understanding these interactions paves the way for novel interventions targeting immune-mediated diseases and optimizing health through microbiome modulation.
Core Tip: This review highlights the critical interplay between the gut microbiome and the host immune system, focusing on how gut microbes and their metabolites, such as short-chain fatty acids, influence immune cell development, inflammatory regulation, and immune homeostasis. It emphasizes recent advances in metagenomics, metabolomics, and single-cell sequencing that have uncovered novel mechanisms of microbiota-driven immune modulation. The discussion also addresses the microbiome’s role in early-life immune education and its implications for autoimmune diseases, inflammation, and cancer immunotherapy, offering insights into emerging microbiome-based therapeutic strategies.
