|
1
|
Xu Z, Zhu Q, Zou J, Lu Y, Wang L, Zou Q, Wang W. Vaginal microbiota transplantation alleviates vaginal atrophy in ovariectomized mice. Sci Rep 2025; 15:8390. [PMID: 40069259 PMCID: PMC11897182 DOI: 10.1038/s41598-025-92881-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 03/03/2025] [Indexed: 03/15/2025] Open
Abstract
Vaginal atrophy is a prevalent symptom in menopausal women, affecting over 50% of older women and patients with loss of ovarian function. The role of factors other than estrogen, such as the vaginal microbiota (VM), in the development of vaginal atrophy has not been fully explored. Therefore, we selected 8-week-old C57 mice with bilateral ovariectomy for experimentation. After four weeks of treatment, we observed that the vaginal epithelium of ovariectomized mice showed signs of atrophy. There were also significant differences in the structure and metabolites of VM. Vaginal transplantation of microbiota from ovary-intact mice significantly alleviated the vaginal atrophy of ovariectomized mice and altered the structure and metabolism of VM. These findings indicate that ovarian activity significantly affects the structure and metabolism of VM. VM of ovary-intact mice may promote vaginal health by upregulating the estrogen receptor alpha gene (ESR1, one-way ANOVA, F4, 25 = 17.76, P < 0.0001) in vaginal epithelial cells in ovariectomized mice, which in turn promotes cell proliferation (the number of vaginal epithelial cell layers, one-way ANOVA, F4, 25 = 28.04, P < 0.0001). Further studies are needed to investigate the interactions between VM and vaginal health. This finding can help develop new therapeutic strategies and interventions for patients suffering from vaginal atrophy.
Collapse
Affiliation(s)
- Zhonglei Xu
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Qiyin Zhu
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Junchi Zou
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Yun Lu
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - LiMing Wang
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China
| | - Qianli Zou
- School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
| | - Wenyan Wang
- The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China.
| |
Collapse
|
|
2
|
Li B, Xiong Y, Guo D, Deng G, Wu H. The gut-reproductive axis: Bridging microbiota balances to reproductive health and fetal development. Int Immunopharmacol 2025; 144:113627. [PMID: 39579544 DOI: 10.1016/j.intimp.2024.113627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/10/2024] [Accepted: 11/11/2024] [Indexed: 11/25/2024]
Abstract
The gut microbiota is a highly complex microbial community residing in the digestive tract of humans and animals, closely linked to host health. Dysbiosis within the gut microbiota has been associated with various diseases. Moreover, it interacts with the female reproductive system's microbiota, influencing maternal reproductive homeostasis. Although the gut microbiota holds potential for treating reproductive system diseases and modulating offspring fertility, research in this domain remains limited. This review examines the relationship between both balanced and imbalanced gut microbiota and reproductive system diseases, as well as their effects on fetal development. It is highlighted that dysbiosis in the gut microbiota may contribute to several reproductive conditions, including polycystic ovary syndrome (PCOS), preeclampsia (PE), endometriosis, gestational diabetes, and reproductive cancers. The abundance of specific gut microbial species or interactions among various species can influence the reproductive system through hormonal pathways and other mechanisms, ultimately affecting pregnancy outcomes and fetal health. Therefore, the concept of the gut-reproductive axis is proposed, emphasizing the significant role of maternal gut microbiota in shaping fetal development, metabolic capacity, and immunity.
Collapse
Affiliation(s)
- Bohao Li
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Yan Xiong
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Dong Guo
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Guohong Deng
- Department of Infectious Diseases, First Affiliated Hospital, Army Medical University, Chongqing, China.
| | - Haibo Wu
- School of Life Sciences, Chongqing University, Chongqing 401331, China; Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China.
| |
Collapse
|
|
3
|
Yu S, Huang F, Huang Y, Yan F, Li Y, Xu S, Zhao Y, Zhang X, Chen R, Chen X, Zhang P. Deciphering the influence of gut and oral microbiomes on menopause for healthy aging. J Genet Genomics 2025:S1673-8527(24)00311-4. [PMID: 39577767 DOI: 10.1016/j.jgg.2024.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 11/24/2024]
Abstract
Menopause is characterized by the cessation of menstruation and a decline in reproductive function, which is an intrinsic component of the aging process. However, it has been a frequently overlooked field of women's health. The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. Therefore, a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota. Our study elucidates the complex interplay between the microbiome and sex hormone levels, explores microbial crosstalk dynamics, and investigates the associations between the microbiome and diseases linked to menopause. Additionally, this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases. Given that menopause can last for approximately 30 years, gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions, which may result in symptomatic relief from menopause and an increase in quality of life in women.
Collapse
Affiliation(s)
- Shuting Yu
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Feiling Huang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China
| | - Yixuan Huang
- Beijing ClouDNA Technology Co., Ltd., Beijing 101407, China
| | - Fangxu Yan
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yi Li
- Hunan Agriculture University, Changsha, Hunan 410128, China
| | - Shenglong Xu
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Yan Zhao
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Xinlei Zhang
- Beijing ClouDNA Technology Co., Ltd., Beijing 101407, China
| | - Rong Chen
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China.
| | - Xingming Chen
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
| | - Peng Zhang
- Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
| |
Collapse
|
|
4
|
Wang MY, Sang LX, Sun SY. Gut microbiota and female health. World J Gastroenterol 2024; 30:1655-1662. [PMID: 38617735 PMCID: PMC11008377 DOI: 10.3748/wjg.v30.i12.1655] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 01/10/2024] [Accepted: 03/05/2024] [Indexed: 03/28/2024] Open
Abstract
The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.
Collapse
Affiliation(s)
- Meng-Yao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Si-Yu Sun
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| |
Collapse
|
|
5
|
Huang F, Cao Y, Liang J, Tang R, Wu S, Zhang P, Chen R. The influence of the gut microbiome on ovarian aging. Gut Microbes 2024; 16:2295394. [PMID: 38170622 PMCID: PMC10766396 DOI: 10.1080/19490976.2023.2295394] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024] Open
Abstract
Ovarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased, preventing ovarian aging has become an essential goal for promoting extended reproductive function and improving bone and genitourinary conditions related to ovarian aging in women. An improved understanding of ovarian aging may ultimately provide tools for the prediction and mitigation of this process. Recent studies have suggested a connection between ovarian aging and the gut microbiota, and alterations in the composition and functional profile of the gut microbiota have profound consequences on ovarian function. The interaction between the gut microbiota and the ovaries is bidirectional. In this review, we examine current knowledge on ovary-gut microbiota crosstalk and further discuss the potential role of gut microbiota in anti-aging interventions. Microbiota-based manipulation is an appealing approach that may offer new therapeutic strategies to delay or reverse ovarian aging.
Collapse
Affiliation(s)
- Feiling Huang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China
| | - Ying Cao
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Jinghui Liang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China
| | - Ruiyi Tang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China
| | - Si Wu
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Peng Zhang
- Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Rare Disease Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | - Rong Chen
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China
| |
Collapse
|
|
6
|
Gilbert JA, Dothard M. Guest editorial from The BMS Annual Lecture 2023. Post Reprod Health 2023; 29:187-189. [PMID: 38059588 DOI: 10.1177/20533691231217150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2023]
Affiliation(s)
- Jack A Gilbert
- Biomedical Sciences Graduate Program and Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Scripps Institution Oceanography, University of California San Diego, La Jolla, CA, USA
| | - Marisol Dothard
- Biomedical Sciences Graduate Program and Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| |
Collapse
|
|
7
|
Xiang D, Zhou E, Wang M, Wang K, Zhou S, Ma Q, Zhong Z, Ye Q, Chen Y, Fan X, Wang Y. Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice. Reprod Biol Endocrinol 2023; 21:49. [PMID: 37208699 DOI: 10.1186/s12958-023-01092-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/11/2023] [Indexed: 05/21/2023] Open
Abstract
BACKGROUND Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix. METHODS In vitro, follicles isolated from 10-12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10-12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination. RESULTS The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts. CONCLUSIONS Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms.
Collapse
Affiliation(s)
- Du Xiang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Encheng Zhou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Mei Wang
- Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Kan Wang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Shujun Zhou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Qing Ma
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Zibiao Zhong
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China
| | - Yun Chen
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, TaiKang Medical School (School of Basic Medical Sciences), Wuhan, 430071, China
| | - Xiaoli Fan
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China.
| | - Yanfeng Wang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University , Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China.
| |
Collapse
|
|
8
|
Dothard MI, Allard SM, Gilbert JA. The effects of hormone replacement therapy on the microbiomes of postmenopausal women. Climacteric 2023; 26:182-192. [PMID: 37051868 DOI: 10.1080/13697137.2023.2173568] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
The sex steroid hormone estrogen plays a number of regulatory roles in female development. During menopause, estrogen synthesis in the ovaries decreases, which results in adverse physiological remodeling and increased risk of disease. Reduced bone density, changes in the community composition profiles of the gut and vaginal microbiome, mood swings and changes in the vaginal environment are to be expected during this time. To alleviate these changes, postmenopausal women can be prescribed hormone replacement therapy (HRT) through the use of exogenous estradiol, often in conjunction with progestin treatment, which re-induces estrogenic action throughout the body. The microbiome and estrogen have a bidirectional, regulatory relationship in the gut, while in the vaginal environment estrogen works indirectly on the microbiome through restoring the vaginal tissue environment that leads to microbial homeostasis. This review discusses what is known about how the gut and vaginal microbiomes of postmenopausal women are responding to HRT, and the potential future of microbe-based therapeutics for symptoms of menopause.
Collapse
Affiliation(s)
- M I Dothard
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - S M Allard
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - J A Gilbert
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| |
Collapse
|
|
9
|
Zhao X, Liu Z, Chen T. Potential Role of Vaginal Microbiota in Ovarian Cancer Carcinogenesis, Progression and Treatment. Pharmaceutics 2023; 15:pharmaceutics15030948. [PMID: 36986809 PMCID: PMC10056320 DOI: 10.3390/pharmaceutics15030948] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/07/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Ovarian cancer represents one of the most challenging gynecologic cancers which still has numerous unknowns on the underlying pathogenesis. In addition to the verified contributors such as genomic predisposition and medical history in the carcinogenesis, emerging evidence points out the potential role of vaginal microbiota in ovarian cancer. Recent studies have underlined the presence of vaginal microbial dysbiosis in cancer cases. Increasing research also indicates the potential correlations between vaginal microbes and cancer carcinogenesis, progression and treatment. Currently, compared with other gynecologic cancers, reports on the roles of vaginal microbiota in ovarian cancer remain scarce and fragmentary. Therefore, in this review, we summarize the roles of vaginal microbiota in various gynecologic diseases, particularly focusing on the potential mechanisms and possible applications of vaginal microbiota in ovarian cancer, giving insight into the involvement of vaginal microbiota in gynecologic cancer treatment.
Collapse
Affiliation(s)
- Xiumiao Zhao
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
- Queen Mary School, Nanchang University, Nanchang 330031, China
| | - Zhaoxia Liu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
- Correspondence: (Z.L.); (T.C.)
| | - Tingtao Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
- National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China
- Correspondence: (Z.L.); (T.C.)
| |
Collapse
|
|
10
|
Hu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L. Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. Gut Microbes 2023; 15:2236749. [PMID: 37559394 PMCID: PMC10416750 DOI: 10.1080/19490976.2023.2236749] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/27/2023] [Accepted: 07/10/2023] [Indexed: 08/11/2023] Open
Abstract
A growing amount of evidence has supported that gut microbiota plays a vital role in the reproductive endocrine system throughout a woman's whole life, and gut microbial β-glucuronidase (gmGUS) is a key factor in regulating host estrogen metabolism. Moreover, estrogen levels also influence the composition as well as the diversity of gut microbiota. In normal condition, the gmGUS-estrogen crosstalk maintains body homeostasis of physiological estrogen level. Once this homeostasis is broken, the estrogen metabolism will be disturbed, resulting in estrogen-related diseases, such as gynecological cancers, menopausal syndrome, etc. together with gut microbial dysbiosis, which may accelerate these pathological processes. In this review, we highlight the regulatory role of gmGUS on the physical estrogen metabolism and estrogen-related diseases, summarize the present evidence of the interaction between gmGUS and estrogen metabolism, and unwrap the potential mechanisms behind them. Finally, gmGUS may become a potential biomarker for early diagnosis of estrogen-induced diseases. Regulating gmGUS activity or transplanting gmGUS-producing microbes shows promise for treating estrogen-related diseases.
Collapse
Affiliation(s)
- Shiwan Hu
- Institute of Metabolic Diseases, Guang’ Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Qiyou Ding
- Institute of Metabolic Diseases, Guang’ Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Zhang
- Institute of Metabolic Diseases, Guang’ Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Mengjiao Kang
- School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Jing Ma
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang’ Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
|
11
|
Qin R, Tian G, Liu J, Cao L. The gut microbiota and endometriosis: From pathogenesis to diagnosis and treatment. Front Cell Infect Microbiol 2022; 12:1069557. [PMID: 36506023 PMCID: PMC9729346 DOI: 10.3389/fcimb.2022.1069557] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 11/07/2022] [Indexed: 11/25/2022] Open
Abstract
Endometriosis is a common gynecological disease, that often leads to pain and infertility. At present, the specific pathogenesis of endometriosis has not been clarified, but it may be closely related to an imbalance of sex hormones in the body, ectopic hyperplasia stimulated by immune inflammation, and invasion and escape based on tumor characteristics. Gut microbiota is associated with many inflammatory diseases. With the further study of the gut microbiota, people are paying increasing attention to its relationship with endometriosis. Studies have shown that there is an association between the gut microbiota and endometriosis. The specific ways and mechanisms by which the gut microbiota participates in endometriosis may involve estrogen, immune inflammation, and tumor characteristics, among others. Therefore, in the future, regulating gut microbiota disorders in various ways can help in the treatment of endometriosis patients. This study reviewed the research on the gut microbiota and endometriosis in order to provide ideas for clinical diagnosis and treatment.
Collapse
Affiliation(s)
- Rui Qin
- Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Gengren Tian
- Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Junbao Liu
- Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Lu Cao
- Department of Obstetrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China,*Correspondence: Lu Cao,
| |
Collapse
|
|
12
|
S-ketamine exerts sex- and dose-dependent anti-compulsive-like effect as monotherapy or in augmentation to fluoxetine. Eur J Pharmacol 2022; 937:175382. [DOI: 10.1016/j.ejphar.2022.175382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/16/2022] [Accepted: 11/03/2022] [Indexed: 11/13/2022]
|
|
13
|
Wang N, Chen L, Yi K, Zhang B, Li C, Zhou X. The effects of microbiota on reproductive health: A review. Crit Rev Food Sci Nutr 2022; 64:1486-1507. [PMID: 36066460 DOI: 10.1080/10408398.2022.2117784] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Reproductive issues are becoming an increasing global problem. There is increasing interest in the relationship between microbiota and reproductive health. Stable microbiota communities exist in the gut, reproductive tract, uterus, testes, and semen. Various effects (e.g., epigenetic modifications, nervous system, metabolism) of dysbiosis in the microbiota can impair gamete quality; interfere with zygote formation, embryo implantation, and embryo development; and increase disease susceptibility, thus adversely impacting reproductive capacity and pregnancy. The maintenance of a healthy microbiota can protect the host from pathogens, increase reproductive potential, and reduce the rates of adverse pregnancy outcomes. In conclusion, this review discusses microbiota in the male and female reproductive systems of multiple animal species. It explores the effects and mechanisms of microbiota on reproduction, factors that influence microbiota composition, and applications of microbiota in reproductive disorder treatment and detection. The findings support novel approaches for managing reproductive diseases through microbiota improvement and monitoring. In addition, it will stimulate further systematic explorations of microbiota-mediated effects on reproduction.
Collapse
Affiliation(s)
- Nan Wang
- College of Animal Sciences, Jilin University, Changchun, China
| | - Lu Chen
- College of Animal Sciences, Jilin University, Changchun, China
| | - Kangle Yi
- Hunan Institute of Animal and Veterinary Science, Changsha, China
| | - Baizhong Zhang
- Hunan Institute of Animal and Veterinary Science, Changsha, China
| | - Chunjin Li
- College of Animal Sciences, Jilin University, Changchun, China
| | - Xu Zhou
- College of Animal Sciences, Jilin University, Changchun, China
| |
Collapse
|
|
14
|
Mei Z, Li D. The role of probiotics in vaginal health. Front Cell Infect Microbiol 2022; 12:963868. [PMID: 35967876 PMCID: PMC9366906 DOI: 10.3389/fcimb.2022.963868] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/05/2022] [Indexed: 11/25/2022] Open
Abstract
Probiotics have been widely used in the treatment of intestinal diseases, but the effect of probiotics on female reproductive tract health is still controversial. Lactobacillus is the most abundant microorganism in the vagina, which is related to the vaginal mucosal barrier. Lactobacillus adheres to the vaginal epithelium and can competitively antagonize the colonization of pathogens. The factors produced by Lactobacillus, such as bacteriocin and hydrogen peroxide (H2O2), can inhibit the growth of pathogenic microorganisms and maintain the low pH environment of the vagina. Probiotics play an important role in maintaining the stability of vaginal microenvironment, improving immune defense and blocking the progression of cervical cancer. We review the research progress of probiotics represented by Lactobacillus in gynecological diseases such as human papilloma virus (HPV) infection, bacterial vaginosis (BV) and Genitourinary Syndrome of Menopause (GSM), so as to provide basis for further exerting the role of probiotics in women’s health.
Collapse
Affiliation(s)
- Zhaojun Mei
- Luzhou Maternal and Child Health Hospital, Luzhou Second People’s Hospital, Luzhou, China
| | - Dandan Li
- University of Chinese Academy of Sciences, Beijing, China
- *Correspondence: Dandan Li,
| |
Collapse
|
|
15
|
Han M, Wang N, Han W, Ban M, Sun T, Xu J. Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential. Front Oncol 2022; 12:902695. [PMID: 35912194 PMCID: PMC9326394 DOI: 10.3389/fonc.2022.902695] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/21/2022] [Indexed: 12/24/2022] Open
Abstract
The human intestine is home to a variety of microorganisms. In healthy populations, the intestinal flora shares a degree of similarity and stability, and they have a role in the metabolism, immunological response, and physiological function of key organs. With the rapid advent of high-throughput sequencing in recent years, several researchers have found that dysbiosis of the human gut microflora potentially cause physical problems and gynecological malignancies among postmenopausal women. Besides, dysbiosis hinders tumor treatment. Nonetheless, the importance of maintaining homeostatic gut microbiota and the effective use of probiotics in the treatment of gynecological malignancies should not be disregarded. Moreover, intestinal flora regulation and the involvement of probiotics as well as associated biologically active substances in gynecological malignancies could be an adjuvant treatment modality related to surgery and chemoradiotherapy in the future. Herein, this article aims to review the potential relationship between gut microorganisms and postmenopausal status as well as gynecologic malignancies; then the relationship between gut microbes and early screening as well as therapeutic aspects. Also, we describe the role of probiotics in the prevention, treatment, and prognosis of gynecologic malignancies.
Collapse
Affiliation(s)
- Mengzhen Han
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Na Wang
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Wenjie Han
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Meng Ban
- Department of Bioinformatics, Liaoning Microhealth Biotechnology Co., Ltd, Shenyang, China
| | - Tao Sun
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Breast Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, China
| | - Junnan Xu
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- *Correspondence: Junnan Xu,
| |
Collapse
|
|
16
|
Cagnacci A, Gambera A, Bonaccorsi G, Xholli A. Relation between blood pressure and genito-urinary symptoms in the years across the menopausal age. Climacteric 2022; 25:395-400. [PMID: 35048756 DOI: 10.1080/13697137.2021.2006176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVES This study aimed to evaluate the relation between blood pressure (BP) or heart rate and genito-urinary symptoms in 504 women across the menopausal age (40-55 years old). METHODS In this multicenter, cross-sectional study, data of office systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were related to the presence of vaginal dryness, dyspareunia, vaginal atrophy (VA), recurrent urinary infection (RUI), hot flushes (HF) or menopausal status. RESULTS Vaginal dryness (coefficient of linear regression β = 5.45, 95% confidence interval [CI] 2.01-8.89; p = 0.0001), VA (β = 3.79, 95% CI 0.84-6.74; p = 0.002) and RUI (β = 3.91, 95% CI 0.72-7.09; p = 0.0163) were independently related to SBP. Vaginal dryness (β = 3.28, 95% CI 0.95-5.61; p = 0.0058), and HF (β = 2.29, 95% CI 0.29-4.28; p = 0.025) were independently related to DBP. Dyspareunia (β = 2.11, 95% CI 0.50-3.72; p = 0.010) was independently related to heart rate. Hypertension was present in 17% of women. When corrected for body mass index (BMI), risk factors for hypertension were VA (OR 2.50, 95% CI 1.43-4.40; p = 0.0014), RUI (OR 1.94 95% CI 1.06-3.52; p = 0.0302) and HF (OR 2.01, 95% CI 1.15-3.50; p = 0.0141). CONCLUSIONS In women across the menopausal age, genito-urinary symptoms, more than HF, are associated with higher values of SBP, DBP, heart rate and hypertension.
Collapse
Affiliation(s)
- A Cagnacci
- Obstetrics and Gynecology Clinic, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Sciences of the Mother and the Infant, IRCCS-Policlinico San Martino, Genova, Italy
| | - A Gambera
- Obstetrics and Gynecology Clinic, ASST Civili Hospital of Brescia, Brescia, Italy
| | - G Bonaccorsi
- Menopause and Osteoporosis Center, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - A Xholli
- Obstetrics and Gynecology Clinic, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Sciences of the Mother and the Infant, IRCCS-Policlinico San Martino, Genova, Italy
| | | |
Collapse
|