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Review

Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis

1
Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
2
Key Laboratory of Fujian Universities Preventive Veterinary Medicine and Biotechnology, Longyan University, Longyan 364012, China
3
Department of Animal Production and Technology, Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir University, Nigde 51240, Turkey
4
College of Agriculture, University of Al Dhaid, Al Sidra, Al Dhaid, Sharjah 7W86+8HP, United Arab Emirates
5
State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural Reclamation Science, Shihezi 832000, China
*
Authors to whom correspondence should be addressed.
Antioxidants 2025, 14(8), 970; https://doi.org/10.3390/antiox14080970 (registering DOI)
Submission received: 9 June 2025 / Revised: 1 August 2025 / Accepted: 6 August 2025 / Published: 7 August 2025
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

Abstract

During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes—autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation—are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy–ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial–metabolic interactions.
Keywords: autophagy; ferroptosis; gut microbiota; placental development; pregnancy outcomes autophagy; ferroptosis; gut microbiota; placental development; pregnancy outcomes

Share and Cite

MDPI and ACS Style

Du, X.; Elsabagh, M.; He, F.; Wu, H.; Zhang, B.; Fan, K.; Wang, M.; Zhang, H. Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis. Antioxidants 2025, 14, 970. https://doi.org/10.3390/antiox14080970

AMA Style

Du X, Elsabagh M, He F, Wu H, Zhang B, Fan K, Wang M, Zhang H. Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis. Antioxidants. 2025; 14(8):970. https://doi.org/10.3390/antiox14080970

Chicago/Turabian Style

Du, Xingyu, Mabrouk Elsabagh, Feiyang He, Huisi Wu, Bei Zhang, Kewei Fan, Mengzhi Wang, and Hao Zhang. 2025. "Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis" Antioxidants 14, no. 8: 970. https://doi.org/10.3390/antiox14080970

APA Style

Du, X., Elsabagh, M., He, F., Wu, H., Zhang, B., Fan, K., Wang, M., & Zhang, H. (2025). Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis. Antioxidants, 14(8), 970. https://doi.org/10.3390/antiox14080970

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