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Volume 27
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10.3390/ijms27010312
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Review

The Placenta–Gut Microbiota Axis in Gestational Diabetes Mellitus: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives

by
Reka Anna Vass
1,2,*,
Eva Miko
2,3,
Viktoria Premusz
2,4,
Sandor G. Vari
5,
Kalman Kovacs
1,2,
Jozsef Bodis
1,2 and
Tibor Ertl
1,2
1
Department of Obstetrics and Gynecology, Medical School, Clinical Centre, University of Pécs, H-7624 Pécs, Hungary
2
National Laboratory on Human Reproduction, University of Pécs, H-7622 Pécs, Hungary
3
Department of Medical Microbiology, Medical School, Clinical Centre, University of Pécs, H-7624 Pécs, Hungary
4
Institute of Physiotherapy and Sport Sciences, Faculty of Health Sciences, University of Pécs, H-7621 Pécs, Hungary
5
International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(1), 312; https://doi.org/10.3390/ijms27010312 (registering DOI)
Submission received: 9 December 2025 / Revised: 24 December 2025 / Accepted: 26 December 2025 / Published: 27 December 2025
(This article belongs to the Special Issue Common Mechanisms in Gestational Diabetes, Preeclampsia, and Coronavirus Disease 2019)
Review Reports Versions Notes

Abstract

Gestational diabetes mellitus (GDM) is a multifactorial metabolic disorder arising from impaired insulin sensitivity and altered maternal–fetal energy regulation. Beyond classical mechanisms involving β-cell dysfunction and pregnancy-induced insulin resistance, emerging evidence suggests a bidirectional interaction between the maternal gut microbiota and the placenta, forming a dynamic placenta–gut axis. Microbial dysbiosis alters levels of metabolites, inflammatory mediators, and bile acids, which influence placental signaling, trophoblast metabolism, immune activation, and nutrient transport. Conversely, the placenta secretes hormones, cytokines, lipids, and exosomal miRNAs that shape maternal metabolism and potentially modulate the gut microbiota. This review synthesizes current mechanistic insights underlying the placenta–gut microbiota axis in GDM, describes immune and metabolic crosstalk, and highlights therapeutic opportunities targeting this inter-organ communication system. Addressing these interactions may advance precision strategies for managing GDM and improving outcomes across generations.
Keywords: gestational diabetes mellitus; placenta; gut microbiota; metabolic inflammation; microbial metabolites; inflammation gestational diabetes mellitus; placenta; gut microbiota; metabolic inflammation; microbial metabolites; inflammation

Share and Cite

MDPI and ACS Style

Vass, R.A.; Miko, E.; Premusz, V.; Vari, S.G.; Kovacs, K.; Bodis, J.; Ertl, T. The Placenta–Gut Microbiota Axis in Gestational Diabetes Mellitus: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives. Int. J. Mol. Sci. 2026, 27, 312. https://doi.org/10.3390/ijms27010312

AMA Style

Vass RA, Miko E, Premusz V, Vari SG, Kovacs K, Bodis J, Ertl T. The Placenta–Gut Microbiota Axis in Gestational Diabetes Mellitus: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives. International Journal of Molecular Sciences. 2026; 27(1):312. https://doi.org/10.3390/ijms27010312

Chicago/Turabian Style

Vass, Reka Anna, Eva Miko, Viktoria Premusz, Sandor G. Vari, Kalman Kovacs, Jozsef Bodis, and Tibor Ertl. 2026. "The Placenta–Gut Microbiota Axis in Gestational Diabetes Mellitus: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives" International Journal of Molecular Sciences 27, no. 1: 312. https://doi.org/10.3390/ijms27010312

APA Style

Vass, R. A., Miko, E., Premusz, V., Vari, S. G., Kovacs, K., Bodis, J., & Ertl, T. (2026). The Placenta–Gut Microbiota Axis in Gestational Diabetes Mellitus: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives. International Journal of Molecular Sciences, 27(1), 312. https://doi.org/10.3390/ijms27010312

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