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Review
. 2025 Dec;17(1):2516702.
doi: 10.1080/19490976.2025.2516702. Epub 2025 Jun 15.

Gut microbiota in regulatory T cell generation and function: mechanisms and health implications

Amit Sharma  1   2 , Garima Sharma  3 , Sin-Hyeog Im  1   3   4
Affiliations
Review

Gut microbiota in regulatory T cell generation and function: mechanisms and health implications

Amit Sharma et al. Gut Microbes. 2025 Dec.

Abstract

The establishment and maintenance of immune homeostasis rely on a dynamic, bidirectional exchange of information between commensal microorganisms and the host immune system. At the center of this process are CD4+Foxp3+ regulatory T cells (Tregs), which have emerged as pivotal mediators to ensure immunological equilibrium. This review explores the sophisticated mechanisms by which the gut microbiota modulates the differentiation, expansion, and functional specialization of Tregs, orchestrating intestinal immune tolerance to support host-microbiota mutualism. We discuss the role of microbial-derived structural components and metabolites in shaping the immunoregulatory fitness of Tregs. Additionally, we explore the impact of gut microbial dysbiosis, where disrupted microbial-immune crosstalk compromises immune tolerance, contributing to the development of inflammatory and autoimmune disorders. Finally, we highlight the potential of microbiota-based strategies to recalibrate intestinal immunity and restore immune tolerance.

Keywords: Microbiome; dysbiosis; live biotherapeutic products; microbial ligands; microbial metabolites; regulatory T cells.

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Conflict of interest statement

S.-H.I. is the founder and major shareholder of ImmunoBiome but has no conflicts of interest in this project. The other authors declare no conflicting financial interests.

Figures

Figure 1.
Figure 1.
Mechanism of microbial antigen-specific pTreg generation in mesenteric lymph nodes.
Figure 2.
Figure 2.
Microbial ligands drive pTreg generation and modulate immune responses.
Figure 3.
Figure 3.
Mechanisms of intestinal treg modulation by microbial short-chain fatty acids (SCFAs).
Figure 4.
Figure 4.
Mechanisms of intestinal treg modulation by microbial tryptophan metabolites.
Figure 5.
Figure 5.
Mechanisms of intestinal treg modulation by microbial bile acid Metabolites.
See this image and copyright information in PMC

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