Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review

The gut microbiota, comprising trillions of bacteria, fungi, and viruses, exists in symbiosis with the host. As the largest microbial ecosystem in the human body. The gut microbiota not only shapes the homeostasis of the intestinal microenvironment through gut-derived metabolites but also exerts reg...

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Main Authors: Lulu Fu, Min Wang, Dan Li, Shuai Ma, Fuliang Zhang, Lianwen Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1624415/full
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author Lulu Fu
Min Wang
Dan Li
Shuai Ma
Fuliang Zhang
Lianwen Zheng
author_facet Lulu Fu
Min Wang
Dan Li
Shuai Ma
Fuliang Zhang
Lianwen Zheng
author_sort Lulu Fu
collection DOAJ
description The gut microbiota, comprising trillions of bacteria, fungi, and viruses, exists in symbiosis with the host. As the largest microbial ecosystem in the human body. The gut microbiota not only shapes the homeostasis of the intestinal microenvironment through gut-derived metabolites but also exerts regulatory effects on the functions of diverse tissues and organs throughout the body via the intricate “gut-distal organ axis” mechanism. Short chain fatty acids, such as acetic acid, propionic acid and butyric acid are high abundance intestinal metabolites, not only influence the intestinal barrier by regulating tight junction proteins, but also affect intestinal peristalsis by regulating gap junction proteins. These microbial metabolites may also play a important role in the formation and maintenance of the key barriers of the reproductive system, such as the ovarian blood follicle barrier, the testicular blood-testis barrier, and the endometrial epithelial barrier. In reproductive system, Gap junction-mediated intercellular communication, facilitated by connexins, proves essential in germ cell maturation, embryo implantation, and spermatogenesis. The dysregulation of these microbial metabolites leading to abnormal tight junction and gap junction protein functions provides novel perspectives for understanding the pathogenesis of reproductive disorders such as polycystic ovary syndrome and premature ovarian failure. This review systematically elucidates the molecular networks through which short-chain fatty acids regulate tight and gap junction proteins, highlighting their potential roles in reproductive physiology.
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publishDate 2025-08-01
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series Frontiers in Cell and Developmental Biology
spelling doaj-art-cd27afd843364e98b7e50644db3efe3e2025-08-22T05:26:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16244151624415Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a reviewLulu Fu0Min Wang1Dan Li2Shuai Ma3Fuliang Zhang4Lianwen Zheng5Reproductive Medical Center, The Second Hospital of Jilin University, Changchun, ChinaReproductive Medical Center, The Second Hospital of Jilin University, Changchun, ChinaReproductive Medical Center, The Second Hospital of Jilin University, Changchun, ChinaReproductive Medical Center, The Second Hospital of Jilin University, Changchun, ChinaStroke center,Department of Neurology, The First Hospital of Jilin University, Changchun, ChinaReproductive Medical Center, The Second Hospital of Jilin University, Changchun, ChinaThe gut microbiota, comprising trillions of bacteria, fungi, and viruses, exists in symbiosis with the host. As the largest microbial ecosystem in the human body. The gut microbiota not only shapes the homeostasis of the intestinal microenvironment through gut-derived metabolites but also exerts regulatory effects on the functions of diverse tissues and organs throughout the body via the intricate “gut-distal organ axis” mechanism. Short chain fatty acids, such as acetic acid, propionic acid and butyric acid are high abundance intestinal metabolites, not only influence the intestinal barrier by regulating tight junction proteins, but also affect intestinal peristalsis by regulating gap junction proteins. These microbial metabolites may also play a important role in the formation and maintenance of the key barriers of the reproductive system, such as the ovarian blood follicle barrier, the testicular blood-testis barrier, and the endometrial epithelial barrier. In reproductive system, Gap junction-mediated intercellular communication, facilitated by connexins, proves essential in germ cell maturation, embryo implantation, and spermatogenesis. The dysregulation of these microbial metabolites leading to abnormal tight junction and gap junction protein functions provides novel perspectives for understanding the pathogenesis of reproductive disorders such as polycystic ovary syndrome and premature ovarian failure. This review systematically elucidates the molecular networks through which short-chain fatty acids regulate tight and gap junction proteins, highlighting their potential roles in reproductive physiology.https://www.frontiersin.org/articles/10.3389/fcell.2025.1624415/fullgut microbiotashort chain fatty acidstight junctiongap junctionreproduction
spellingShingle Lulu Fu
Min Wang
Dan Li
Shuai Ma
Fuliang Zhang
Lianwen Zheng
Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
Frontiers in Cell and Developmental Biology
gut microbiota
short chain fatty acids
tight junction
gap junction
reproduction
title Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
title_full Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
title_fullStr Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
title_full_unstemmed Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
title_short Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review
title_sort microbial metabolites short chain fatty acids tight junction gap junction and reproduction a review
topic gut microbiota
short chain fatty acids
tight junction
gap junction
reproduction
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1624415/full
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