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      Influence of the gut microbiota on endometriosis: Potential role of chenodeoxycholic acid and its derivatives

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          Abstract

          The gut microbiota (GM) has received extensive attention in recent years, and its key role in the establishment and maintenance of health and in the development of diseases has been confirmed. A strong correlation between the GM and the progression of endometriosis (EMS) has been observed in emerging research. Alterations in the composition and function of the GM have been described in many studies on EMS. In contrast, the GM in the environment of EMS, especially the GM metabolites, such as bile acids and short-chain fatty acids that are related to the pathogenesis of EMS, can promote disease progression. Chenodeoxycholic acid (CDCA), as one of the primary bile acids produced in the liver, is metabolized by various enzymes derived from the GM and is critically important in maintaining intestinal homeostasis and regulating lipid and carbohydrate metabolism and innate immunity. Given that the complexity of CDCA as a signalling molecule and the interaction between the GM and EMS have not been clarified, the role of the CDCA and GM in EMS should be understood from a novel perspective. However, few articles on the relationship between CDCA and EMS have been reviewed. Therefore, we review the available and possible potential links between CDCA, the GM and EMS and put forward the hypothesis that CDCA and its derivative obeticholic acid can improve the symptoms of EMS through the GM.

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          An obesity-associated gut microbiome with increased capacity for energy harvest.

          The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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            Gut microbiota, metabolites and host immunity.

            The microbiota - the collection of microorganisms that live within and on all mammals - provides crucial signals for the development and function of the immune system. Increased availability of technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host-microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system.
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              Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

              Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                22 August 2022
                2022
                : 13
                : 954684
                Affiliations
                [1] 1 Department of Traditional Chinese Gynecology , The First Affiliated Hospital of Naval Medical University , Shanghai, China
                [2] 2 Department of Pharmaceutical Sciences , Beijing Institute of Radiation Medicine , Beijing, China
                Author notes

                Edited by: Ping Zhou, Chinese Academy of Medical Sciences and Peking Union Medical College, China

                Reviewed by: Tao Yang, Guizhou University of Traditional Chinese Medicine, China

                Zheng Ping, Third Affiliated Hospital of Guangzhou Medical University, China

                Makoto Makishima, Nihon University, Japan

                *Correspondence: Zhexin Ni, nizxzg@ 123456163.com ; Chaoqin Yu, chqyu81@ 123456163.com
                [ † ]

                These authors have contributed equally to this work

                This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology

                Article
                954684
                10.3389/fphar.2022.954684
                9442031
                36071850
                30cfb9c3-6ac2-495b-9156-4941f8adccf5
                Copyright © 2022 Li, Wang, Ding, Sun, Ni and Yu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 May 2022
                : 27 July 2022
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                chenodeoxycholic acid,gut microbiota,endometriosis,inflammation,bile acids

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