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Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review)

  • Authors:
    • Nanjian Luo
    • Han Hu
    • Xiaoting Zeng
    • Yi Huan Zhang
    • Qi Deng
    • En Ni Tang
    • Yu Hu
  • View Affiliations / Copyright

    Affiliations: Department of Reproductive Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 268
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    Published online on: July 31, 2026
       https://doi.org/10.3892/mmr.2026.13979
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Abstract

Recent studies have indicated the relationships between the human reproductive system, gut microbiota and immune crosstalk. These interactions can influence pregnancy outcomes, which occasionally result in adverse consequences for the mother and fetus. However, key questions remain unresolved, such as identifying the microbiota capable of modulating immune cells during pregnancy. The present review aimed to investigate the relationship between microbiota and T cell types and to clarify the mechanism through which these interactions occur. In pregnancy‑related disease models, it is still unclear whether T helper cell (Th17)/regulatory T cells (Treg cells) are generated in situ or migrate into inflamed tissues. The present review explored the association of gastrointestinal dysbiosis with the female reproductive system and the role of the maternal‑fetal interface. In particular, the effect of gut microbiota‑derived short‑chain fatty acids, bile acids, indoles and their derivatives on immune signaling networks is discussed. Furthermore, the effects of these networks on infectious, metabolic and female pregnancy periods are summarized. Finally, the translational potential of modulating gut microbiota through probiotics and dietary interventions to restore immune homeostasis and improve pregnancy outcomes in Recurrent pregnancy loss (RPL) is also evaluated. The present review aimed to assist patients in developing a more profound comprehension of the underlying causes of unexplained RPL and broaden the spectrum of potential therapeutic strategies for infertility.
View Figures

Figure 1

SCFAs regulate CD4+ T cells,
affecting RPL. SCFAs, short-chain fatty acids; IL-10, interleukin
10; Th17, T helper cell 17; TNF-α, tumor necrosis factor α; Treg,
regulatory T cell.

Figure 2

BAs inhibit the NF-κB pathway,
affecting the balance between inflammasome and Th17 during RPL.
BAs, bile acids; FXR, farnesoid X receptor; MKK3/6,
mitogen-activated protein kinase kinase 3 and 6; P38, p38
mitogen-activated protein kinase; NF-κB, nuclear factor κB; NFF,
non-filterable factor; MMC, mucosal mast cell; Treg, T-regulatory
cell; NGF, nerve growth factor.

Figure 3

Indoles drive AHR, affecting the
early differentiation of Th17 cells to regulate RPL. TH1, T helper
cell 1; Treg, T-regulatory cell; Tr1, T regulatory type 1; IDO,
indoleamine 2;3-dioxygenase; ARH, aryl hydrocarbon receptor; LPS,
lipopolysaccharides; CpG, cytosine-phosphate-guanine; TLR,
Toll-like receptors; P, properdin; STAT1, signal transducer and
activator of transduction 1; NF-κB, nuclear factor κB.

Figure 4

Mechanism of crosstalk between gut
microbiota and immune cells in RPL. BAs, bile acids; SCFAs,
short-chain fatty acids; TCR, T-cell receptor; ILC3, group 3 innate
lymphoid cell; MHC-1, major histocompatibility complex class I;
IL-2, interleukin 2; Th17 cell, T helper cell 17; NK T cell,
natural killer T cell; FOXP3, forkhead box P3.
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Copy and paste a formatted citation
Spandidos Publications style
Luo N, Hu H, Zeng X, Zhang YH, Deng Q, Tang EN and Hu Y: Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review). Mol Med Rep 34: 268, 2026.
APA
Luo, N., Hu, H., Zeng, X., Zhang, Y.H., Deng, Q., Tang, E.N., & Hu, Y. (2026). Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review). Molecular Medicine Reports, 34, 268. https://doi.org/10.3892/mmr.2026.13979
MLA
Luo, N., Hu, H., Zeng, X., Zhang, Y. H., Deng, Q., Tang, E. N., Hu, Y."Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review)". Molecular Medicine Reports 34.4 (2026): 268.
Chicago
Luo, N., Hu, H., Zeng, X., Zhang, Y. H., Deng, Q., Tang, E. N., Hu, Y."Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review)". Molecular Medicine Reports 34, no. 4 (2026): 268. https://doi.org/10.3892/mmr.2026.13979
Copy and paste a formatted citation
x
Spandidos Publications style
Luo N, Hu H, Zeng X, Zhang YH, Deng Q, Tang EN and Hu Y: Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review). Mol Med Rep 34: 268, 2026.
APA
Luo, N., Hu, H., Zeng, X., Zhang, Y.H., Deng, Q., Tang, E.N., & Hu, Y. (2026). Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review). Molecular Medicine Reports, 34, 268. https://doi.org/10.3892/mmr.2026.13979
MLA
Luo, N., Hu, H., Zeng, X., Zhang, Y. H., Deng, Q., Tang, E. N., Hu, Y."Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review)". Molecular Medicine Reports 34.4 (2026): 268.
Chicago
Luo, N., Hu, H., Zeng, X., Zhang, Y. H., Deng, Q., Tang, E. N., Hu, Y."Gut microbiota‑immune crosstalk in recurrent pregnancy loss: Mechanisms and therapeutic perspectives (Review)". Molecular Medicine Reports 34, no. 4 (2026): 268. https://doi.org/10.3892/mmr.2026.13979
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