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Qiao Y, Chen H, Guo J, Zhang X, Liang X, Wei L, Wang Q, Bi H, Gao T. A Study of Sex Differences in the Biological Pathways of Stress Regulation in Mice. CNS Neurosci Ther 2025; 31:e70433. [PMID: 40365748 PMCID: PMC12076126 DOI: 10.1111/cns.70433] [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: 03/26/2024] [Revised: 03/10/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Stress is closely related to life, and it can also cause many mental disorders. However, there are significant sex differences in neuropsychiatric disorders associated with stress, particularly in depression, where the lifetime risk of depression in women is approximately twice that of men. However, the specific mechanism of this process has not been explained in detail. METHODS Chronic restraint stress (CRS) + chronic and unpredictable mild stress (CUMS) was used to simulate social stress, and behavioral experiments, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, and metabolomics analysis of hippocampal and intestinal contents were performed. RESULTS The results showed that stress induced anxiety-like behavior in female mice and depression-like behavior in male mice. Sex differences in behavior may be related to monoamine neurotransmitters, hyperactivity of HPA axis, inflammatory factors, gut microbiota, and brain-gut metabolism. It is worth noting that stress caused opposite trends in DA (dopamine) levels, abundance of f-lactobaciliaceae, and levels of metabolites (1, 2-distearoyl-SN-glycero-3-phosphocholine) and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z)) in male and female mice. CONCLUSION The difference in neurotransmitter levels, the disorder of gut microbiota, and the abnormal brain and gut metabolism may lead to the gender difference in stress behavior.
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Affiliation(s)
- Yajun Qiao
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- School of PsychologyChengdu Medical CollegeChengduChina
- University of Chinese Academy of SciencesBeijingChina
| | - Hanxi Chen
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
| | - Juan Guo
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- School of PsychologyChengdu Medical CollegeChengduChina
| | - Xingfang Zhang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- Medical College, Qinghai UniversityXiningChina
| | - Xinxin Liang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- School of PsychologyChengdu Medical CollegeChengduChina
- University of Chinese Academy of SciencesBeijingChina
| | - Lixin Wei
- University of Chinese Academy of SciencesBeijingChina
- CAS Key Laboratory of Tibetan Medicine ResearchNorthwest Institute of Plateau Biology, Chinese Academy of SciencesXiningChina
| | - Qiannan Wang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- School of PsychologyChengdu Medical CollegeChengduChina
| | - Hongtao Bi
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety EvaluationNorthwest Institute of Plateau Biology, Chinese Academy of ScienceXiningChina
- University of Chinese Academy of SciencesBeijingChina
| | - Tingting Gao
- School of PsychologyChengdu Medical CollegeChengduChina
- Department of PsychiatryThe People's Hospital of Jiangmen, Southern Medical UniversityJiangmenChina
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Pakpahan C, Laurus G, Hartanto MC, Singh R, Saharan A, Darmadi D, Rezano A, Wasian G. Potential relationship of the gut microbiome with testosterone level in men: a systematic review. PeerJ 2025; 13:e19289. [PMID: 40256744 PMCID: PMC12007503 DOI: 10.7717/peerj.19289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 03/18/2025] [Indexed: 04/22/2025] Open
Abstract
The gut microbiome influences the metabolism and health of several organs beyond the gut and has recently gained considerable attention. The gut plays a central role in food digestion, absorption, nutrition, and general health. Hence, the gut microbiome has become a research subject for almost all health conditions. Imbalance or dysbiosis in the gut microbiome can cause different health issues in men, including reproductive and sexual health issues associated with testosterone levels. Several studies have investigated the relationship between the gut microbiome and testosterone levels. In this systematic review, we aimed to examine the relationship between the gut microbiome and testosterone levels in men. Literature searches were conducted by scanning PubMed, ProQuest, EBSCO, Taylor & Francis Online, Wiley Online, Springer Link, Web of Science, Google Scholar, and Science Direct databases for relevant keywords following the preferred reporting items for the systematic review guidelines. This review included cross-sectional, case-control, retrospective, and prospective cohort studies. Quality assessment was conducted using the Newcastle-Ottawa Scale. We found a significant positive correlation between the gut microbiome and testosterone levels in men. Several microbes play substantial roles in testosterone production. Mechanisms have been proposed as factors that contribute to testosterone levels, namely the hypothalamus-pituitary-gonad axis modulation, androgen metabolism, and intestinal homeostasis, by balancing the bone morphogenic protein (BMP) and the Wnt diverse microbiome. Ruminococcus showed a stronger correlation with testosterone levels than other microorganisms. The gut microbiome has complex correlations with testosterone metabolism. However, the microbiome with the most significant influence on testosterone levels cannot be easily identified and requires further research.
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Affiliation(s)
- Cennikon Pakpahan
- Andrology Study Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Geraldo Laurus
- Andrology Study Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Markus Christian Hartanto
- Andrology Study Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Rajender Singh
- Division of Endocrinology, Central Drug Research Institute India, Lucknow, Uttar Pradesh, India
| | - Ankur Saharan
- Faculty of Medicine, Amity University India, Noida, Uttar Pradesh, India
- Department of Human Genetic, McGill University, Montreal, Quebec, Canada
| | - Darmadi Darmadi
- Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, North Sumatera, Indonesia
| | - Andri Rezano
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia
| | - Gito Wasian
- Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
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Qiao Y, Guo J, Xiao Q, Wang J, Zhang X, Liang X, Wei L, Bi H, Gao T. A study on the differences in the gut microbiota and metabolism between male and female mice in different stress periods. Exp Biol Med (Maywood) 2025; 250:10204. [PMID: 40008145 PMCID: PMC11851196 DOI: 10.3389/ebm.2025.10204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 01/28/2025] [Indexed: 02/27/2025] Open
Abstract
The sex difference in depression has long been an unsolved issue. Women are twice as likely to suffer from depression as men. However, there were significant differences in the composition of gut microbiota between women and men. There is a lack of studies linking sex differences in depression to microbiota, and the specific mechanisms of this process have not been explained in detail. The main purpose of this study was to explore the gender differences in the intestinal tract of male and female depressed mice. In this study, chronic restraint stress (CRS) mouse models were used to simulate chronic stress, and behavioral tests were conducted, including the open field test (OFT), tail suspension test (TST) and forced swimming test (FST). Microbial diversity analysis and metabolomics were performed on collected mouse feces. The results showed that female mice were highly active and prone to anxious behavior before stress, and the levels of f-Rikenellaceae, f-Ruminococcaceae and 16α-hydroxyestrone were significantly different from those in male mice. After 21 days (Days) of stress, female mice showed depression-like behavior, and the levels of f-Erysipelotrichaceae, 5α-pregnane-3,20-dione, and 2-hydroxyestradiol were significantly different from those in male mice. After 14 days of stress withdrawal, the depression-like behavior continued to worsen in female mice, and the levels of 5α-pregnane-3,20-dione, estrone glucuronide and f-Erysipelotrichaceae were significantly different from those in male mice. In summary, female mice have stronger stress sensitivity and weaker resilience than male mice, which may be related to differences in bacterial diversity and estrogen metabolism disorders.
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Affiliation(s)
- Yajun Qiao
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
- School of Psychology, Chengdu Medical College, Chengdu, China
- CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China
| | - Juan Guo
- Qinghai Provincial Traffic Hospital, Xining, China
| | - Qi Xiao
- Emergency Department, The First Hospital of Qinhuangdao, Qinhuangdao, China
| | - Jianv Wang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
- CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China
| | - Xingfang Zhang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
- Medical College, Qinghai University, Xining, China
| | - Xinxin Liang
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
- CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China
| | - Lixin Wei
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
- CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China
| | - Hongtao Bi
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China
| | - Tingting Gao
- School of Psychology, Chengdu Medical College, Chengdu, China
- Department of Psychiatry, The People’s Hospital of Jiangmen, Southern Medical University, Jiangmen, China
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Ma ZS. Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes. BMC Biol 2024; 22:284. [PMID: 39639265 PMCID: PMC11622641 DOI: 10.1186/s12915-024-02025-6] [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: 12/16/2022] [Accepted: 09/30/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism. RESULTS Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses. CONCLUSIONS This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.
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Affiliation(s)
- Zhanshan Sam Ma
- Computational Biology and Medical Ecology Lab, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
- Department of Entomology, College of Plant Protection, Hebei Agricultural University, Baoding, China.
- Microbiome Medicine and Advanced AI Lab, Cambridge, MA, 02138, USA.
- Faculty of Arts and Science, Harvard University, Cambridge, MA, 02138, USA.
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Mao L, Liu A, Zhang X. Effects of Intermittent Fasting on Female Reproductive Function: A Review of Animal and Human Studies. Curr Nutr Rep 2024; 13:786-799. [PMID: 39320714 DOI: 10.1007/s13668-024-00569-1] [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] [Accepted: 08/20/2024] [Indexed: 09/26/2024]
Abstract
PURPOSE OF REVIEW Intermittent fasting has gained significant attention, yet a comprehensive understanding of its impact on female reproductive health is lacking. This review aims to fill this gap by examining various intermittent fasting regimens and their effects on female reproductive function, along with potential mechanisms. RECENT FINDINGS In healthy non-overweight/obese or pregnant animal models, alternate-day fasting (ADF) and an 8-h time-restricted feeding (TRF) window may have adverse effects on reproductive function. However, these regimens show potential to mitigate negative consequences induced by a high-fat diet (HFD) or environmental exposure. A 10-h TRF demonstrates benefits in improving fertility in both normal-weight and HFD-fed animal models. In women with overweight/obesity or polycystic ovary syndrome (PCOS), the 5:2 diet and TRF significantly reduce the free androgen index while elevating sex hormone binding globulin, promising improvements in menstrual regulation. For pregnant Muslim women, available data do not strongly indicate adverse effects of Ramadan fasting on preterm delivery, but potential downsides to maternal weight gain, neonatal birthweight, and long-term offspring health need consideration. Factors linking intermittent fasting to female reproductive health include the circadian clock, gut microbiota, metabolic regulators, and modifiable lifestyles. Drawing definitive conclusions remains challenging in this evolving area. Nonetheless, our findings underscore the potential utility of intermittent fasting regimens as a therapeutic approach for addressing menstruation irregularities and infertility in women with obesity and PCOS. On the other hand, pregnant women should remain cognizant of potential risks associated with intermittent fasting practices.
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Affiliation(s)
- Lei Mao
- Department of Women's Health, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Aixia Liu
- Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
| | - Xiaohui Zhang
- Department of Women's Health, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
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Wang J, Liu H, Kou X, Zhang Y, Wang Y, Chen C, Xiang Z, Wang X, Su C, Liu Y. Toxic effects of DEHP and MEHP on gut-liver axis in rats via intestinal flora and metabolomics. iScience 2024; 27:111135. [PMID: 39555414 PMCID: PMC11565036 DOI: 10.1016/j.isci.2024.111135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 07/12/2024] [Accepted: 10/07/2024] [Indexed: 11/19/2024] Open
Abstract
Di (2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor and commonly used as a plasticizer. Exposure to DEHP and its active metabolite mono-2-ethylhexyl phthalate (MEHP) can lead to adverse health consequences; however, the toxic mechanism is remains unclear. In this research, male and female rats were exposed to DEHP and MEHP by oral gavage for 60 consecutive days. Pathological analysis revealed that DEHP and MEHP exposure could affect liver, heart, kidney, and testis tissues, as well as alter biochemical indicators. Metagenomics (16S rRNA gene sequencing) analysis indicated that DEHP and MEHP could reduce the diversity and alter the composition of the gut microbiota. Toxic exposure also affected the levels of short chain fatty acids (SCFAs), with noticeable variations between genders. Metabolomic analysis revealed that DEHP and MEHP could influence bile acids, amino acids, hormones, and lipids. These results demonstrate that exposure to DEHP and MEHP can induce toxicity in rats via the gut-liver axis.
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Affiliation(s)
- Jiaqi Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
- Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
| | - Hongwei Liu
- Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Xiwen Kou
- College of Foreign Languages, Northeastern University, Shenyang, China
| | - Yuxin Zhang
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
| | - Yang Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
- Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
| | - Changlan Chen
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
| | - Zheng Xiang
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
- Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
| | - Xin Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
- Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
| | - Ce Su
- Pharmacy Department, Shenyang Tenth Peoples Hospital, Shenyang, China
| | - Yangcheng Liu
- School of Pharmaceutical Science, Liaoning University, Shenyang, China
- Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
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Kwack DW, Lee S, Lee DH, Kim DW. Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients. Clin Neurol Neurosurg 2024; 246:108556. [PMID: 39299008 DOI: 10.1016/j.clineuro.2024.108556] [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: 07/23/2024] [Revised: 09/12/2024] [Accepted: 09/14/2024] [Indexed: 09/22/2024]
Abstract
OBJECTIVE Seizures can be triggered by a variety of endogenous or exogenous factors. We hypothesized that alterations in the gut microbiome may be a seizure precipitant and analyzed the composition and characteristics of the gut microbiome in epilepsy patients who experienced an abrupt seizure exacerbation without a clear seizure precipitant. METHODS We prospectively enrolled 25 adult patients with epilepsy and collected fecal samples on the admission and after seizure recovery for next-generation sequencing analysis. We performed nonparametric paired t-test analysis to evaluate changes in the gut microbiota as seizures worsened and when it recovered and also estimated alpha and beta diversities in each category. RESULTS A total of 19 patients (13 males) aged between 19 and 78 years (mean 45.2 years) were included in the study. The composition of the gut microbiota underwent a significant change following an abrupt seizure exacerbation. At the phylum level, the relative abundance of Fusobacteria and Synergistetes was decreased in the seizure recovery state compared to the acute seizure exacerbation. A similar trend was observed at the lower hierarchical levels, with a decrease in the relative abundance of Fusobacteria, Tissierellia, and Synergistia at the class level, and that of Synergistales, Tissierellales, and Fusobacteriales at the order level. At the family level, the relative abundance of Fusobacteriaceae and Staphylococcaceae was decreased, whereas that of Leuconostocaceae was increased. No statistical differences were observed in alpha and beta diversity between the pre- and post-acute seizure exacerbation periods. SIGNIFICANCE Our study suggests that the changes in Fusobacteriaceae and Lecuonostocaceae may be associated with acute seizure exacerbation in epilepsy patients. Given that Fusobacteriaceae are associated with various systemic diseases due to their invasive properties and that Leuconostocaceae are known to produce GABA, our results may suggest a gut microbiome-based treatment option for epilepsy patients.
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Affiliation(s)
- Dong Won Kwack
- Department of Neurology, Konkuk University Hospital, Seoul, South Korea
| | - Sunghee Lee
- Ildong Pharmaceutical CO., Ltd., Hwaseong, Gyeonggi, South Korea
| | - Dong-Hoon Lee
- Ildong Pharmaceutical CO., Ltd., Hwaseong, Gyeonggi, South Korea
| | - Dong Wook Kim
- Department of Neurology, Konkuk University Hospital, Seoul, South Korea.
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Liu Y, Lin S, Wang C, Li T, Zheng G, Sun W, An L, Bai Y, Wu F. Sex-Specific Effects of Environmental Exposure to the Antimicrobial Agents Benzalkonium Chloride and Triclosan on the Gut Microbiota and Health of Zebrafish ( Danio rerio). ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:15450-15462. [PMID: 39141879 DOI: 10.1021/acs.est.4c03205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
The use of disinfectants containing benzalkonium chloride (BAC) has become increasingly widespread in response to triclosan (TCS) restrictions and the COVID-19 pandemic, leading to the increasing presence of BAC in aquatic ecosystems. However, the potential environmental health impacts of BAC on fish remain poorly explored. In this study, we show that BAC and TCS can induce the gut dysbiosis in zebrafish (Danio rerio), with substantial effects on health. Breeding pairs of adult zebrafish were exposed to environmentally relevant concentrations of BAC and TCS (0.4-40 μg/L) for 42 days. Both BAC and TCS exposure perturbed the gut microbiota, triggering the classical NF-κB signaling pathway and resulting in downstream pathological toxicity associated with inflammatory responses, histological damage, inhibited ingestion, and decreased survival. These effects were dose-dependent and sex-specific, as female zebrafish were more susceptible than male zebrafish. Furthermore, we found that BAC induced toxicity to a greater extent than the restricted TCS at environmentally relevant concentrations, which is particularly concerning. Our results suggest that environmental exposure to antimicrobial chemicals can have ecological consequences by perturbing the gut microbiota, a previously underappreciated target of such chemicals. Rigorous ecological analysis should be conducted before widely introducing replacement antimicrobial compounds into disinfecting products.
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Affiliation(s)
- Yueyue Liu
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
- College of Water Science, Beijing Normal University, Beijing 100875, China
| | - Siyi Lin
- School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
| | - Chen Wang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Tong Li
- Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Guomao Zheng
- School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
| | - Wen Sun
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Lihui An
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Yingchen Bai
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Fengchang Wu
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
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Hu C, Guo CL, Lau HCH, Shi F, Zhang Z, Guo G, Liu G, Chen Y, Lau LHS, Zhang L, Sun X, Wong SH, Zhang L, She J, Yu J. Appendix removal affects the subsequent cancer risk in Asian adults: A territory-wide population-based cohort study. Cancer Lett 2024; 598:217087. [PMID: 38964732 DOI: 10.1016/j.canlet.2024.217087] [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: 04/24/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 07/06/2024]
Abstract
Human appendix is critical for the maintenance of intestinal homeostasis. Appendicectomy has been the optimal treatment of acute appendicitis, yet the cancer incidence after appendix removal remains unclear. In this territory-wide retrospective cohort study, adult participants who underwent appendicectomy from 2000 to 2018 were retrieved from a population database (n = 43,983), while matched reference participants were retrieved as controls (n = 85,853). After appendicectomy, the overall cancer risk was significantly increased (subdistribution hazard ratio (SHR) = 1.124) compared to the non-appendicectomy group. Appendicectomy-treated males had higher cancer risk than males without appendicectomy (SHR = 1.197), while such difference was not observed in female participants. Significant increase in cancer risk was also observed in elder participants (age >60) with appendicectomy (SHR = 1.390). Appendicectomy was positively correlated with the risk of digestive tract and respiratory cancers including colon (SHR = 1.440), pancreas (SHR = 1.930), and trachea, bronchus, and lung (SHR = 1.394). In contrast, the risk of liver cancer was markedly decreased after appendicectomy (SHR = 0.713). In conclusion, we reported the association of appendicectomy with subsequent cancer incidence. These findings highlight the potential complication after appendix removal and the necessity of post-operative management to monitor and prevent long-term adverse events.
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Affiliation(s)
- Chenhao Hu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Cosmos Liutao Guo
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry Cheuk-Hay Lau
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhe Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Gang Guo
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Gaixia Liu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yinnan Chen
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Louis Ho-Shing Lau
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lei Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xuejun Sun
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Sunny Hei Wong
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Lei Zhang
- Artificial Intelligence and Modelling in Epidemiology Program, Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia; Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Jun Yu
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
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10
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Pérez-Prieto I, Rodríguez-Santisteban A, Altmäe S. Beyond the reproductive tract: gut microbiome and its influence on gynecological health. Curr Opin Obstet Gynecol 2024:00075197-990000000-00151. [PMID: 38598655 DOI: 10.1097/gco.0000000000000952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
PURPOSE OF REVIEW The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.
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Affiliation(s)
- Inmaculada Pérez-Prieto
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada
- Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | | | - Signe Altmäe
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada
- Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Brennan C, Chan K, Kumar T, Maissy E, Brubaker L, Dothard MI, Gilbert JA, Gilbert KE, Lewis AL, Thackray VG, Zarrinpar A, Knight R. Harnessing the power within: engineering the microbiome for enhanced gynecologic health. REPRODUCTION AND FERTILITY 2024; 5:e230060. [PMID: 38513356 PMCID: PMC11046331 DOI: 10.1530/raf-23-0060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/18/2024] [Indexed: 03/23/2024] Open
Abstract
Abstract Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions. Lay summary Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.
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Affiliation(s)
- Caitriona Brennan
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Division of Biological Sciences, University of California San Diego, La Jolla, California, USA
| | - Kristina Chan
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
| | - Tanya Kumar
- Medical Scientist Training Program, University of California San Diego, La Jolla, California, USA
| | - Erica Maissy
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
| | - Linda Brubaker
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California, USA
| | - Marisol I Dothard
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
| | - Jack A Gilbert
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
| | - Katharine E Gilbert
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Amanda L Lewis
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California, USA
| | - Varykina G Thackray
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
| | - Amir Zarrinpar
- Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
- Medical Scientist Training Program, University of California San Diego, La Jolla, California, USA
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, California, USA
- Institute of Diabetes and Metabolic Health, University of California San Diego, La Jolla, California, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA
- Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, California, USA
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12
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Rio P, Caldarelli M, Chiantore M, Ocarino F, Candelli M, Gasbarrini A, Gambassi G, Cianci R. Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective. Cells 2024; 13:526. [PMID: 38534370 PMCID: PMC10969451 DOI: 10.3390/cells13060526] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/11/2024] [Accepted: 03/15/2024] [Indexed: 03/28/2024] Open
Abstract
The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.
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Affiliation(s)
- Pierluigi Rio
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Mario Caldarelli
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Monica Chiantore
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Francesca Ocarino
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Marcello Candelli
- Department of Emergency, Anesthesiological and Reanimation Sciences, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Giovanni Gambassi
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
| | - Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.); (F.O.); (A.G.); (G.G.)
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13
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Jia L, Jiang Y, Wu L, Fu J, Du J, Luo Z, Guo L, Xu J, Liu Y. Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis. Nat Commun 2024; 15:1617. [PMID: 38388542 PMCID: PMC10883948 DOI: 10.1038/s41467-024-45473-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 01/25/2024] [Indexed: 02/24/2024] Open
Abstract
Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.
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Affiliation(s)
- Lu Jia
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Yiyang Jiang
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Lili Wu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Jingfei Fu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Juan Du
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Zhenhua Luo
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Lijia Guo
- Department of Orthodontics School of Stomatology, Capital Medical University, Beijing, P. R. China
| | - Junji Xu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China.
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, P. R. China.
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14
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Zhou X, Gao Y, Wei J, Luo J, Wang Y, Yue M, Wang B, Hong D, Chen T, Fang X. The intestinal microbiota exerts a sex-specific influence on neuroinflammation in a Parkinson's disease mouse model. Neurochem Int 2024; 173:105661. [PMID: 38157887 DOI: 10.1016/j.neuint.2023.105661] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/17/2023] [Accepted: 12/21/2023] [Indexed: 01/03/2024]
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterised by chronic and progressive symptoms; it is more prevalent in men than in women. The sex-specific influence of the intestinal microbiota has been associated with some neurodegenerative diseases, but the relationship with PD is currently unclear. In this study, we treated mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model, and we utilised an antibiotic cocktail (Abx) to deplete the intestinal microbiota to evaluate the influence of the intestinal microbiota on male and female PD mice. MPTP treatment obviously caused bradykinesia and low mobility in female and male mice. Meanwhile, Abx treatment exerted a greater effect on male mice than female mice. Western blotting and immunofluorescence revealed that male mice treated with MPTP had higher expression of α-synuclein and proteins related to neuroinflammation and intestinal inflammation based on activation of glial cells and the TLR4-MyD88 signalling pathway. The sex-specific differences could be due to the different composition of the intestinal microbiota. Specifically, female mice had significantly higher abundance of Allobaculum, Turicibacter and Ruminococcus than male mice. Moreover, the abundance of the probiotic genus Bifidobacterium showed opposite trends in male and female mice. Our results indicate that the intestinal microbiota has an important effect on PD mice, especially male mice, by influencing neuroinflammation through the microbiota-gut-brain axis. In the future, there should be a focus on providing more reliable evidence for the pathogenesis and precise treatment of PD.
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Affiliation(s)
- Xiaoting Zhou
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Yuan Gao
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China; Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Jing Wei
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China
| | - Jie Luo
- School of Public Health, Nanchang University, Nanchang, 330031, China
| | - Yun Wang
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Mengyun Yue
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Bo Wang
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Daojun Hong
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Tingtao Chen
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China.
| | - Xin Fang
- Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
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15
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Rodríguez-Barreto D, Sanz-González JC, Martín MV, Arrieta JM, Almansa E. Sex-specific bacterial microbiome variation in octopus vulgaris skin. Front Microbiol 2024; 14:1233661. [PMID: 38318128 PMCID: PMC10842966 DOI: 10.3389/fmicb.2023.1233661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 12/11/2023] [Indexed: 02/07/2024] Open
Abstract
Growing knowledge of the host-microbiota of vertebrates has shown the prevalence of sex-specific differences in the microbiome. However, there are virtually no studies assessing sex-associated variation in the microbiome of cephalopods. Here we assess sex-specific variation in the common octopus (Octopus vulgaris) skin microbiome using amplicon sequencing targeting the V4 hypervariable region of prokaryote 16S rRNA genes. Skin and mantle-associated mucus was collected from wild adult individuals of common Octopus (Octopus vulgaris) (9 males and 7 females of similar size). There were no significant differences in the alpha diversity of microbial communities associated with skin or mantle mucosa between sexes. However, our results clearly indicate that adult octopus males and females have a distinct microbial community composition in both skin and mantle associated mucus communities, with female microbiome being dominated by Firmicutes (48.1%), while that of males contained a majority of Proteobacteria (60.5%), with Firmicutes representing only 3.30%, not finding significant differentiation in the microbial communities between the tissues explored. The dominance of different taxa in the skin of O. vulgaris females and males (e.g., Mycoplasmatales and Lactococcus in females and Rhizobiales and Rhodobacteriales in males) suggests a sex-specific symbiosis in which those microbes benefit from easy access to distinct substrates present in female and male skin, respectively. Given the lack of differences in size between specimens of both sexes in this study, we hypothesize differences in hormone profile, as well as behavioral or ecological differences between sexes in the wild, as the main drivers of microbiome differentiation between sexes. Most knowledge of cephalopod microbiota is limited to the digestive tract and the reproductive system. However, cephalopod skin is an organ with a plethora of functions. This is a first attempt to characterize cephalopod skin microbiota and determine sex influence on it.
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Affiliation(s)
- Deiene Rodríguez-Barreto
- Canary Islands Oceanographic Center, Spanish Institute of Oceanography (IEO-CSIC), Santa Cruz de Tenerife, Spain
- University of La Laguna, Santa Cruz de Tenerife, Spain
| | - Juan Carlos Sanz-González
- Canary Islands Oceanographic Center, Spanish Institute of Oceanography (IEO-CSIC), Santa Cruz de Tenerife, Spain
| | - M. Virginia Martín
- Canary Islands Oceanographic Center, Spanish Institute of Oceanography (IEO-CSIC), Santa Cruz de Tenerife, Spain
| | - Jesús M. Arrieta
- Canary Islands Oceanographic Center, Spanish Institute of Oceanography (IEO-CSIC), Santa Cruz de Tenerife, Spain
| | - Eduardo Almansa
- Canary Islands Oceanographic Center, Spanish Institute of Oceanography (IEO-CSIC), Santa Cruz de Tenerife, Spain
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16
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Adams DR, Xu LJ, Vickery TW, Scangas GA, Bleier BS, Gray ST, Metson R. The Impact of Gender on Long-Term Quality of Life After Sinus Surgery for Chronic Rhinosinusitis. Laryngoscope 2023; 133:3319-3326. [PMID: 37114661 DOI: 10.1002/lary.30719] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/01/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023]
Abstract
OBJECTIVE To identify the impact of gender on the clinical outcomes of endoscopic sinus surgery (ESS) through the comparison of quality of life measures in female and male patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN Prospective observational cohort study. METHODS Patients with CRS completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and EuroQol 5-Dimension Survey (EQ-5D) preoperatively and annually for 5 years following ESS. Health utility values (HUV) were calculated from EQ-5D scores. Comparisons of cohort characteristics were performed with chi-square and t-tests. A multivariable linear mixed effects model evaluated changes in SNOT-22 and HUV over time by gender. RESULTS Among the 1268 patients (54% female) enrolled, 789 and 343 completed postoperative surveys at one and 5 years, respectively. Preoperatively, females experienced more severe symptoms: mean SNOT-22 score (51.1 ± 20.9 female vs. 44.7 ± 20.0 male, p < 0.001) and HUV (0.80 ± 0.14 female vs. 0.84 ± 0.11 male, p < 0.001). These gender differences were resolved by year one postoperatively (SNOT-22: p = 0.083; HUV: p = 0.465). Two years after surgery, however, females reported more severe symptoms (SNOT-22: 25.6 ± 20.7 female vs. 21.5 ± 17.4 male, p = 0.005; HUV: 0.88 ± 0.12 female vs. 0.90 ± 0.11 male, p = 0.018), a difference that persisted at year five. These gender-related differences remained after adjusting for age, race, ethnicity, nasal polyps, history of prior ESS, and smoking status (p < 0.001). Within-subject improvement was comparable between genders (SNOT-22: p = 0.869; HUV: p = 0.611). CONCLUSION Females with CRS reported more severe symptoms both before and 5 years after surgery compared to their male counterparts. Understanding the mechanism behind these gender-related differences is important for optimizing CRS treatment. LEVEL OF EVIDENCE 2 Laryngoscope, 133:3319-3326, 2023.
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Affiliation(s)
- Dara R Adams
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - Lucy J Xu
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - Thad W Vickery
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - George A Scangas
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - Benjamin S Bleier
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - Stacey T Gray
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - Ralph Metson
- Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A
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17
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Toro-Ascuy D, Cárdenas JP, Zorondo-Rodríguez F, González D, Silva-Moreno E, Puebla C, Nunez-Parra A, Reyes-Cerpa S, Fuenzalida LF. Microbiota Profile of the Nasal Cavity According to Lifestyles in Healthy Adults in Santiago, Chile. Microorganisms 2023; 11:1635. [PMID: 37512807 PMCID: PMC10384449 DOI: 10.3390/microorganisms11071635] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/18/2023] [Accepted: 06/19/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND The respiratory microbiome is dynamic, varying between anatomical niches, and it is affected by various host and environmental factors, one of which is lifestyle. Few studies have characterized the upper respiratory tract microbiome profile according to lifestyle. We explored the association between lifestyles and microbiota profiles in the upper respiratory tract of healthy adults. METHODS We analyzed nasal samples from 110 healthy adults who were living in Santiago, Chile, using 16S ribosomal RNA gene-sequencing methods. Volunteers completed a structured questionnaire about lifestyle. RESULTS The composition and abundance of taxonomic groups varied across lifestyle attributes. Additionally, multivariate models suggested that alpha diversity varied in the function of physical activity, nutritional status, smoking, and the interaction between nutritional status and smoking, although the significant impact of those variables varied between women and men. Although physical activity and nutritional status were significantly associated with all indexes of alpha diversity among women, the diversity of microbiota among men was associated with smoking and the interaction between nutritional status and smoking. CONCLUSIONS The alpha diversity of nasal microbiota is associated with lifestyle attributes, but these associations depend on sex and nutritional status. Our results suggest that future studies of the airway microbiome may provide a better resolution if data are stratified for differences in sex and nutritional status.
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Affiliation(s)
- Daniela Toro-Ascuy
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
| | - Juan P Cárdenas
- Centro de Genómica y Bioinformática, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, Chile
- Escuela de Biotecnología, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, Chile
| | - Francisco Zorondo-Rodríguez
- Departamento de Gestión Agraria, Facultad Tecnológica, Universidad de Santiago de Chile, Santiago 8910060, Chile
| | - Damariz González
- Centro de Genómica y Bioinformática, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, Chile
| | - Evelyn Silva-Moreno
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
| | - Carlos Puebla
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
| | - Alexia Nunez-Parra
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
| | - Sebastián Reyes-Cerpa
- Centro de Genómica y Bioinformática, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, Chile
- Escuela de Biotecnología, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, Chile
| | - Loreto F Fuenzalida
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
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18
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Bykowska-Derda A, Kałużna M, Garbacz A, Ziemnicka K, Ruchała M, Czlapka-Matyasik M. Intake of Low Glycaemic Index Foods but Not Probiotics Is Associated with Atherosclerosis Risk in Women with Polycystic Ovary Syndrome. Life (Basel) 2023; 13:799. [PMID: 36983954 PMCID: PMC10052525 DOI: 10.3390/life13030799] [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: 01/31/2023] [Revised: 03/08/2023] [Accepted: 03/11/2023] [Indexed: 03/18/2023] Open
Abstract
Women with polycystic ovary syndrome (PCOS) are at high cardiometabolic risk. The atherogenic index of plasma (AIP) strongly predicts atherosclerosis. Some studies suggest that probiotic intake may lower AIP. This study analysed the relationship between the frequency of dietary intake of low glycaemic index (prebiotic) and probiotic foods and atherosclerosis risk in women with PCOS. METHODS A total of 127 women were divided into two groups: AIP over 0.11 (highAIP) and AIP ≤ 0.11 (lowAIP). The KomPAN® questionnaire was used to measure food frequency intake; pro-healthy, non-healthy, low glycaemic and probiotic dietary indexes were calculated based on daily food consumption. Body composition was measured by air displacement plethysmography (BodPod). AIP was calculated as a logarithm of triglycerides and high-density lipoproteins from plasma. RESULTS The highAIP group was 63% less likely to consume low glycaemic index foods three or more times a day than the lowAIP group. The HighAIP group was also 62% less likely to consume buckwheat, oats, whole-grain pasta or coarse-ground grains at least a few times a week. Pro-healthy foods tended to be less frequently consumed by the highAIP group, when adjusted for BMI and age. CONCLUSION Women with PCOS at high risk of atherosclerosis consumed less low glycaemic index foods than women with a low risk of atherosclerosis. Intake of high-fibre, low glycaemic index foods could prevent atherosclerosis in women with PCOS; however, the effect of probiotic food intake remains unclear.
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Affiliation(s)
- Aleksandra Bykowska-Derda
- Department of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego 31, 60-624 Poznan, Poland;
| | - Małgorzata Kałużna
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Agnieszka Garbacz
- Student Science Club of Dieticians, Poznan University of Life Sciences, Wojska Polskiego 31, 60-624 Poznan, Poland
| | - Katarzyna Ziemnicka
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Magdalena Czlapka-Matyasik
- Department of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego 31, 60-624 Poznan, Poland;
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19
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Pretorius L, Smith C. Tyramine-induced gastrointestinal dysregulation is attenuated via estradiol associated mechanisms in a zebrafish larval model. Toxicol Appl Pharmacol 2023; 461:116399. [PMID: 36716863 DOI: 10.1016/j.taap.2023.116399] [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: 09/28/2022] [Revised: 01/06/2023] [Accepted: 01/19/2023] [Indexed: 01/30/2023]
Abstract
Development of targeted therapeutics to alleviate gastrointestinal (GI) inflammation and its debilitating consequences are required. In this context, the trace aminergic system may link together sex, diet and inflammation. Utilising a zebrafish larval model of GI inflammation, the current study aimed to investigate mechanisms by which excess amounts of trace amines (TAs) may influence GI health. In addition, we probed the potential role of 17β-estradiol (E2) and its receptors, given the known female-predominance of many GI disorders. To assess GI functionality and integrity, live imaging techniques (neutral red staining) and post-mortem immunofluorescent staining of tight junction proteins (occludin and ZO-1) were analyzed respectively. In addition, behavioural assays, as an indication of overall wellbeing, as well as whole body H2O2 and prostaglandin E2 assays were performed to inform on oxidative and inflammatory status. Excess β-phenethylamine (PEA), tryptamine (TRP) and ρ-tyramine (TYR) resulted in adverse GI and systemic effects. In this regard, clear beneficial effects of E2 to modulate the effects of PEA, TRP and TYR was evident. Moreover, agmatine displayed potential protective effects on GI epithelium and whole body oxidative status, however, potential to induce systemic inflammation suggests the importance of dosage and administration optimisation. Taken together, TYR seems like the most prominent TA to have damaging GI effects, feasibly exacerbating GI inflammation. In this context, the relative lack of E2 may provide mechanistic insights into the reported female-predominance of GI disorders. Moreover, an effective therapeutic in this context may be required to maintain GI TA load despite fluctuating E2 levels.
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Affiliation(s)
- L Pretorius
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
| | - C Smith
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
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20
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Wang L, Tang L, Zhai D, Song M, Li W, Xu S, Jiang S, Meng H, Liang J, Wang Y, Zhang B. The role of the sex hormone-gut microbiome axis in tumor immunotherapy. Gut Microbes 2023; 15:2185035. [PMID: 36880651 PMCID: PMC10012946 DOI: 10.1080/19490976.2023.2185035] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
Accumulating evidence suggested that both gut microbiome and sex play a critical role in the efficacy of immune checkpoint blockade therapy. Considering the reciprocal relationship between sex hormones and gut microbiome, the sex hormone-gut microbiome axis may participate in the regulation of the response to immune checkpoint inhibitors (ICIs). In this review, it was attempted to summarize the current knowledge about the influences of both sex and gut microbiome on the antitumor efficacy of ICIs and describe the interaction between sex hormones and gut microbiome. Accordingly, this review discussed the potential of enhancing the antitumor efficacy of ICIs through regulating the levels of sex hormones through manipulation of gut microbiome. Collectively, this review provided reliable evidence concerning the role of the sex hormone-gut microbiome axis in tumor immunotherapy.
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Affiliation(s)
- Luoyang Wang
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Lei Tang
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Dongchang Zhai
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Meiying Song
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Wei Li
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Shuo Xu
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Suli Jiang
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Haining Meng
- School of Emergency Medicine, Qingdao University, Qingdao, China
| | - Jie Liang
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Yingying Wang
- Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Bei Zhang
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China
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21
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Stefanaki C, Bacopoulou F, Chrousos GP. Gut Microsex/Genderome, Immunity and the Stress Response in the Sexes: An Updated Review. SEXES 2022; 3:533-545. [DOI: 10.3390/sexes3040039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
Abstract
Sex has been universally acknowledged as a confounding factor in every type of biological study, while there are strong sex differences in morbidity along the lifespan. Humans have almost identical genomes (99.2%), yet minor variance in their DNA produces remarkable phenotypic diversity across the human population. On the other hand, metagenomic analysis of the human microbiome is more variable, depending on the sex, lifestyle, geography, and age of individuals under study. Immune responses in humans also exhibit variations, with an especially striking sexual dimorphism, which is at play in several other physiologic processes. Sex steroids have noticeable effects on the composition of the human microbiome along the lifespan, accompanied by parallel changes in immunity and the stress response. Gut microsex/genderome, a recently coined term, defines the sexually dimorphic gut microbiome. Apart from the sex steroids, the stress hormones are also at play in the proliferation of microbes. This review summarizes the concept of gut microsex/genderome under the prism of recent studies on the interrelations of the sexually dimorphic microbiome with immunity and stress.
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Affiliation(s)
- Charikleia Stefanaki
- University Research Institute for Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, “Agia Sophia” Children’s Hospital, School of Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Flora Bacopoulou
- University Research Institute for Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, “Agia Sophia” Children’s Hospital, School of Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - George P. Chrousos
- University Research Institute for Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, “Agia Sophia” Children’s Hospital, School of Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece
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22
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Sivasankari R, Usha B. Reshaping the Gut Microbiota Through Lifestyle Interventions in Women with PCOS: A Review. Indian J Microbiol 2022; 62:351-363. [PMID: 35974920 PMCID: PMC9375820 DOI: 10.1007/s12088-022-01019-8] [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: 11/16/2021] [Accepted: 03/30/2022] [Indexed: 11/05/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disorder evolving as a global threat to women's health. However, its multifactorial etiology causes difficulty in eliminating it. The interrelation between the gut microbiota and metabolic disorders has been trending recently, giving rise to new opportunities on the etiology and pathogenesis of PCOS. Lifestyle interventions such as healthy diet, physical exercises, and behavioral interventions such as regulation of stress and sleep cycles have been identified to improve the symptoms of PCOS across the endocrinological, metabolic and psychological scales and are recommended as the first line of treatment for PCOS. The impact of the unhealthy lifestyle factors on intestinal dysbiosis that cause PCOS is summarized in this review. This review also provides an insight on the therapeutic approaches that primarily target the gut microbiota and offers novel gut microflora-associated treatment strategies for PCOS. Further, this survey also highlights the need for the implementation of lifestyle management strategies and strongly recommends a healthy and stress-free lifestyle to promote gut health and manage PCOS.
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Affiliation(s)
- Ramadurai Sivasankari
- Department of Genetic Engineering, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Tamil Nadu 603 203 India
| | - Balasundaram Usha
- Department of Genetic Engineering, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Tamil Nadu 603 203 India
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23
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Maffei S, Forini F, Canale P, Nicolini G, Guiducci L. Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease. Int J Mol Sci 2022; 23:ijms23137154. [PMID: 35806159 PMCID: PMC9266921 DOI: 10.3390/ijms23137154] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 01/27/2023] Open
Abstract
The available evidence indicates a close connection between gut microbiota (GM) disturbance and increased risk of cardiometabolic (CM) disorders and cardiovascular (CV) disease. One major objective of this narrative review is to discuss the key contribution of dietary regimen in determining the GM biodiversity and the implications of GM dysbiosis for the overall health of the CV system. In particular, emerging molecular pathways are presented, linking microbiota-derived signals to the local activation of the immune system as the driver of a systemic proinflammatory state and permissive condition for the onset and progression of CM and CV disease. We further outline how the cross-talk between sex hormones and GM impacts disease susceptibility, thereby offering a mechanistic insight into sexual dimorphism observed in CVD. A better understanding of these relationships could help unravel novel disease targets and pave the way to the development of innovative, low-risk therapeutic strategies based on diet interventions, GM manipulation, and sex hormone analogues.
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Affiliation(s)
- Silvia Maffei
- Department of Gynecological and Cardiovascular Endocrinology, CNR-Tuscany Region, G. Monasterio Foundation, Via G. Moruzzi 1, 56124 Pisa, Italy;
| | - Francesca Forini
- CNR Institute of Clinical Physiology, Via G Moruzzi 1, 56124 Pisa, Italy; (P.C.); (G.N.); (L.G.)
- Correspondence:
| | - Paola Canale
- CNR Institute of Clinical Physiology, Via G Moruzzi 1, 56124 Pisa, Italy; (P.C.); (G.N.); (L.G.)
| | - Giuseppina Nicolini
- CNR Institute of Clinical Physiology, Via G Moruzzi 1, 56124 Pisa, Italy; (P.C.); (G.N.); (L.G.)
| | - Letizia Guiducci
- CNR Institute of Clinical Physiology, Via G Moruzzi 1, 56124 Pisa, Italy; (P.C.); (G.N.); (L.G.)
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24
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Parodi G, Leite G, Pimentel ML, Barlow GM, Fiorentino A, Morales W, Pimentel M, Weitsman S, Mathur R. The Response of the Rodent Gut Microbiome to Broad-Spectrum Antibiotics Is Different in Males and Females. Front Microbiol 2022; 13:897283. [PMID: 35756061 PMCID: PMC9218673 DOI: 10.3389/fmicb.2022.897283] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/16/2022] [Indexed: 12/02/2022] Open
Abstract
Gut microbiome composition is different in males and females, but sex is rarely considered when prescribing antibiotics, and sex-based differences in gut microbiome recovery following antibiotic treatment are poorly understood. Here, we compared the effects of broad-spectrum antibiotics on both the stool and small bowel microbiomes in male and female rats. Adult male and female Sprague Dawley rats were exposed to a multi-drug antibiotic cocktail for 8 days, or remained unexposed as controls. Following cessation of antibiotics, rats were monitored for an additional 13-day recovery period prior to euthanasia. Baseline stool microbiome composition was similar in males and females. By antibiotic exposure day 8 (AbxD8), exposed male rats exhibited greater loss of stool microbial diversity compared to exposed females, and the relative abundance (RA) of numerous taxa were significantly different in exposed males vs. exposed females. Specifically, RA of phylum Proteobacteria and genera Lactobacillus, Sutterella, Akkermansia, and Serratia were higher in exposed males vs. exposed females, whereas RA of phyla Firmicutes and Actinobacteria and genera Turicibacter and Enterococcus were lower. By 13 days post antibiotics cessation (PAbxD13), the stool RA of these and other taxa remained significantly different from baseline, and also remained significantly different between exposed males and exposed females. RA of phyla Firmicutes and Actinobacteria and genus Enterococcus remained lower in exposed males vs. exposed females, and genus Sutterella remained higher. However, RA of phylum Proteobacteria and genus Akkermansia were now also lower in exposed males vs. females, whereas RA of phylum Bacteroidetes and genus Turicibacter were now higher in exposed males. Further, the small bowel microbiome of exposed rats on PAbxD13 was also significantly different from unexposed controls, with higher RA of Firmicutes, Turicibacter and Parabacteroides in exposed males vs. females, and lower RA of Bacteroidetes, Proteobacteria, Actinobacteria, Oscillospira, Sutterella, and Akkermansia in exposed males vs. females. These findings indicate that broad-spectrum antibiotics have significant and sex-specific effects on gut microbial populations in both stool and the small bowel, and that the recovery of gut microbial populations following exposure to broad-spectrum antibiotics also differs between sexes. These findings may have clinical implications for the way antibiotics are prescribed.
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Affiliation(s)
- Gonzalo Parodi
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Gabriela Leite
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Maya L Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Gillian M Barlow
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Alyson Fiorentino
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Walter Morales
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States.,Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, United States
| | - Stacy Weitsman
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States
| | - Ruchi Mathur
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States.,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, CA, United States
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25
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Martyniuk CJ, Buerger AN, Vespalcova H, Rudzanova B, Sohag SR, Hanlon AT, Ginn PE, Craft SL, Smetanova S, Budinska E, Bisesi JH, Adamovsky O. Sex-dependent host-microbiome dynamics in zebrafish: Implications for toxicology and gastrointestinal physiology. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART D, GENOMICS & PROTEOMICS 2022; 42:100993. [PMID: 35533547 DOI: 10.1016/j.cbd.2022.100993] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 03/04/2022] [Accepted: 04/18/2022] [Indexed: 06/14/2023]
Abstract
The physiology of males and females can be vastly different, complicating interpretation of toxicological and physiological data. The objectives of this study were to elucidate the sex differences in the microbiome-gastrointestinal (GI) transcriptome of adult zebrafish. We compared microbial composition and diversity in both males and females fed the same diet and housed in the same environment. There were no sex-specific differences in weight gain nor gastrointestinal morphology based on histopathology. There was no difference in gut microbial diversity, richness (Shannon and Chao1 index) nor predicted functional composition of the microbiome between males and females. Prior to post-hoc correction, male zebrafish showed higher abundance for the bacterial families Erythrobacteraceae and Lamiaceae, both belonging to the phyla Actinobacteria and Proteobacteria. At the genus level, Lamia and Altererythrobacter were more dominant in males and an unidentified genus in Bacteroidetes was more abundant in females. There were 16 unique differentially expressed transcripts in the gastrointestinal tissue between male and female zebrafish (FDR corrected, p < 0.05). Relative to males, the mRNA expression for trim35-9, slc25a48, chchd3b, csad, and hsd17b3 were lower in female GI while cyp2k6, adra2c, and bckdk were higher in the female GI. Immune and lipid-related gene network expression differed between the sexes (i.e., cholesterol export and metabolism) as well as networks related to gastric motility, gastrointestinal system absorption and digestion. Such data provide clues as to putative differences in gastrointestinal physiology between male and female zebrafish. This study identifies host-transcriptome differences that can be considered when interpreting the microgenderome of zebrafish in studies investigating GI physiology and toxicology of fishes.
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Affiliation(s)
- Christopher J Martyniuk
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Amanda N Buerger
- Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA
| | - Hana Vespalcova
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Barbora Rudzanova
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Shahadur R Sohag
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Amy T Hanlon
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Pamela E Ginn
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
| | - Serena L Craft
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
| | - Sona Smetanova
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Eva Budinska
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Joseph H Bisesi
- Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA
| | - Ondrej Adamovsky
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA; Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic.
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26
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Del Castillo-Izquierdo Á, Mayneris-Perxachs J, Fernández-Real JM. Bidirectional relationships between the gut microbiome and sexual traits. Am J Physiol Cell Physiol 2022; 322:C1223-C1229. [PMID: 35508190 DOI: 10.1152/ajpcell.00116.2022] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/20/2022] [Accepted: 04/21/2022] [Indexed: 11/22/2022]
Abstract
The human gut microbiota is known to be shaped by a variety of environmental factors (diet, drugs, geography, and sanitation) and host intrinsic factors (age and sexual development). The differences in gut microbiota between sexes are minimal before adulthood and late adulthood, and marked during adulthood. For instance, consistent higher relative abundances of Akkermansia and Ruminococcus have been observed in adult women compared with men and most studies have found higher relative abundances of Prevotella and Fusobacterium (linked to a diet rich in animal proteins) in adult men compared with women. The gut microbiota taxonomy and functionality present in women is more similar to men once reached the menopause. In fact, specific taxa have been associated with the levels of different sexual hormones and their precursors in blood. The gut microbiota composition and circulating testosterone levels are also tightly linked to the extent that microbial signatures can predict its levels in blood. At the same time, the gut microbiota participates in the metabolism of sexual hormones, with some bacteria being able to metabolize gonadal steroid hormones (one example is 3β-hydroxysteroid dehydrogenase, a testosterone degrading enzyme). In summary, the relationships between the gut microbiome and sexual traits are bidirectional. In addition, other phenotypes and cultural gender-related factors could drive sex-related differences. It is important to note that other members of the microbiome (Archaea, viruses, and fungi) have been largely unexplored in relation to this sexual dimorphism. More research is needed on this topic.
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Affiliation(s)
- Ángela Del Castillo-Izquierdo
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain
- CIBERobn Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
| | - Jordi Mayneris-Perxachs
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain
- CIBERobn Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
| | - José Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain
- CIBERobn Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain
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27
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Gottfried S. Women: Diet, Cardiometabolic Health, and Functional Medicine. Phys Med Rehabil Clin N Am 2022; 33:621-645. [DOI: 10.1016/j.pmr.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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28
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Kim N. Sexual Dimorphism in the Gut Microbiome: Microgenderome or Microsexome? Author's Reply. J Neurogastroenterol Motil 2022; 28:334. [PMID: 35362461 PMCID: PMC8978115 DOI: 10.5056/jnm22007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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29
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Mulak A, Larauche M, Taché Y. Sexual Dimorphism in the Gut Microbiome: Microgenderome or Microsexome? J Neurogastroenterol Motil 2022; 28:332-333. [PMID: 35362460 PMCID: PMC8978118 DOI: 10.5056/jnm21242] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Muriel Larauche
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Yvette Taché
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
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30
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De Francia S, Ferretti A, Chiara F, Allegra S, Mancardi D, Allice TG, Milia MG, Gregori G, Burdino E, Avanzini C, Ghisetti V, Durio A. The Influence of Sex, Gender, and Age on COVID-19 Data in the Piedmont Region (Northwest Italy): The Virus Prefers Men. Life (Basel) 2022; 12:life12050643. [PMID: 35629311 PMCID: PMC9148110 DOI: 10.3390/life12050643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/22/2022] [Accepted: 04/24/2022] [Indexed: 01/08/2023] Open
Abstract
Several important sex and gender differences in the clinical manifestation of diseases have been known for a long time but are still underestimated. The infectious Coronavirus 2019 disease pandemic has provided evidence of the importance of a sex and gender-based approach; it mainly affected men with worse symptomatology due to a different immune system, which is stronger in women, and to the Angiotensin-converting enzyme 2 and Transmembrane protease serine 2 roles which are differently expressed among the sexes. Additionally, women are more inclined to maintain social distance and smoke less. Analysis of data on the infectious Coronavirus 2019 disease testing from people admitted to the Amedeo di Savoia Hospital, a regional referral center for infectious diseases, has been applied to the whole of 2020 data (254,640 records). A high percentage of data in the dataset was not suitable due to a lack of information or entering errors. Among the suitable samples, records have been analyzed for positive/negative outcomes, matching records for unique subjects (N = 123,542), to evaluate individual recurrence of testing. Data are presented in age and sex-disaggregated ways. Analyses of the suitable sample also concerned the relation between testing and hospital admission motivation and symptoms. Our analysis indicated that a sex and gender-based approach is mandatory for patients and the National Health System’s sustainability.
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Affiliation(s)
- Silvia De Francia
- Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy; (F.C.); (S.A.); (D.M.)
- Correspondence:
| | | | - Francesco Chiara
- Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy; (F.C.); (S.A.); (D.M.)
| | - Sarah Allegra
- Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy; (F.C.); (S.A.); (D.M.)
| | - Daniele Mancardi
- Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy; (F.C.); (S.A.); (D.M.)
| | - Tiziano Giacomo Allice
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Maria Grazia Milia
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Gabriella Gregori
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Elisa Burdino
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Claudio Avanzini
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Valeria Ghisetti
- Laboratory of Microbiology and Virology ASL Turin, 10149 Turin, Italy; (T.G.A.); (M.G.M.); (G.G.); (E.B.); (C.A.); (V.G.)
| | - Alessandra Durio
- Department of Economics and Statistics “Cognetti de Martiis”, University of Turin, 10153 Turin, Italy;
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Gut microbiota and its role in stress-induced hyperalgesia: gender-specific responses linked to different changes in serum metabolites. Pharmacol Res 2022; 177:106129. [DOI: 10.1016/j.phrs.2022.106129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/31/2022] [Accepted: 02/08/2022] [Indexed: 12/13/2022]
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32
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Li H, Lu L, Chen R, Li S, Xu D. Exploring Sexual Dimorphism in the Intestinal Microbiota of the Yellow Drum ( Nibea albiflora, Sciaenidae). Front Microbiol 2022; 12:808285. [PMID: 35069512 PMCID: PMC8767002 DOI: 10.3389/fmicb.2021.808285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/06/2021] [Indexed: 11/13/2022] Open
Abstract
Most of fish species exhibit striking sexual dimorphism, particularly during growth. There are also sexual dimorphisms of internal organs and biological functions, including those of intestinal microbiota, which likely plays a key role in growth. In this study, the growth and intestinal microbiota of the female, male, and all-female Nibea albiflora (yellow drums) were comprehensively analyzed. The caged culture female and all-female yellow drums showed higher growth rates than males. A further analysis of the intestinal microbiota showed a significant difference in diversity between females and males in the summer, whereas there were no significant differences in the diversity and richness between females and males in the winter. In contrast, a significant difference in richness was observed between all-female and male fish, regardless of the season. Although the main composition of the intestinal microbiota showed no significant sex differences, the community structure of the intestinal microbiota of yellow drums did. Furthermore, the correlations between intestinal microbial communities are likely to be influenced by sex. The ecological processes of the intestinal microbial communities of the yellow drums showed clear sexual dimorphism. Further network analysis revealed that, although the main components of the network in the intestinal microbiota of female, male, and all-female fish were similar, the network structures showed significant sex differences. The negative interactions among microbial species were the dominant relationships in the intestinal ecosystem, and Bacteroidetes, Firmicutes, and Proteobacteria were identified as the functional keystone microbes. In addition, the functional pathways in the intestinal microbiota of yellow drums showed no significant sexual or seasonal differences. Based on the findings of this study, we gain a comprehensive understanding of the interactions between sex, growth, and intestinal microbiota in yellow drums.
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Affiliation(s)
- Haidong Li
- School of Fishery, Zhejiang Ocean University, Zhoushan, China
| | - Lei Lu
- School of Fishery, Zhejiang Ocean University, Zhoushan, China.,Key Lab of Mariculture and Enhancement of Zhejiang Province, Zhejiang Marine Fisheries Research Institute, Zhoushan, China
| | - Ruiyi Chen
- Key Lab of Mariculture and Enhancement of Zhejiang Province, Zhejiang Marine Fisheries Research Institute, Zhoushan, China
| | - Shanshan Li
- School of Fishery, Zhejiang Ocean University, Zhoushan, China
| | - Dongdong Xu
- Key Lab of Mariculture and Enhancement of Zhejiang Province, Zhejiang Marine Fisheries Research Institute, Zhoushan, China
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33
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Abstract
As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.
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Affiliation(s)
- Xinyu Qi
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China,Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
| | - Chuyu Yun
- Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yanli Pang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China,Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, China,CONTACT Yanli Pang M.D.,Ph.D Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
| | - Jie Qiao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China,Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, China,National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China,Jie Qiao M.D., Ph.D Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
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34
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Harada M. Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research. Reprod Med Biol 2022; 21:e12487. [PMID: 36310656 PMCID: PMC9601867 DOI: 10.1002/rmb2.12487] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/01/2022] [Accepted: 09/15/2022] [Indexed: 11/05/2022] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women and has lifelong effects on health. Methods In this review, I discuss the pathophysiology of PCOS. First, I summarize our current understanding of the etiology and pathology of PCOS, then, discuss details of two representative environmental factors involved in the pathogenesis of PCOS. Finally, I present perspectives regarding the directions of future research. Main findings The pathophysiology of PCOS is heterogeneous and shaped by the interaction of reproductive dysfunction and metabolic disorders. Hyperandrogenism and insulin resistance exacerbate one another during the development of PCOS, which is also affected by dysfunction of the hypothalamus-pituitary-ovarian axis. PCOS is a highly heritable disorder, and exposure to certain environmental factors causes individuals with predisposing genetic factors to develop PCOS. The environmental factors that drive the development of PCOS pathophysiology make a larger contribution than the genetic factors, and may include the intrauterine environment during the prenatal period, the follicular microenvironment, and lifestyle after birth. Conclusion On the basis of this current understanding, three areas are proposed to be subjects for future research, with the ultimate goals of developing therapeutic and preventive strategies and providing appropriate lifelong management, including preconception care.
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Affiliation(s)
- Miyuki Harada
- Department of Obstetrics and Gynecology, Faculty of MedicineThe University of TokyoTokyoJapan
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35
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Kusamoto A, Harada M, Azhary JMK, Kunitomi C, Nose E, Koike H, Xu Z, Urata Y, Kaku T, Takahashi N, Wada-Hiraike O, Hirota Y, Koga K, Fujii T, Osuga Y. Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome-like phenotypes in prenatally androgenized female mice. FASEB J 2021; 35:e21971. [PMID: 34653284 DOI: 10.1096/fj.202101051r] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/11/2021] [Accepted: 09/20/2021] [Indexed: 12/11/2022]
Abstract
It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the β-diversity differed from control at 8 weeks. However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice. Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life.
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Affiliation(s)
- Akari Kusamoto
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Miyuki Harada
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Jerilee M K Azhary
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chisato Kunitomi
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Emi Nose
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Koike
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Zixin Xu
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoko Urata
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tetsuaki Kaku
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nozomi Takahashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Wada-Hiraike
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasushi Hirota
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kaori Koga
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoyuki Fujii
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
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36
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Annunziata G, Ciampaglia R, Capò X, Guerra F, Sureda A, Tenore GC, Novellino E. Polycystic ovary syndrome and cardiovascular risk. Could trimethylamine N-oxide (TMAO) be a major player? A potential upgrade forward in the DOGMA theory. Biomed Pharmacother 2021; 143:112171. [PMID: 34536755 DOI: 10.1016/j.biopha.2021.112171] [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: 06/16/2021] [Revised: 09/03/2021] [Accepted: 09/05/2021] [Indexed: 11/26/2022] Open
Abstract
Several studies reported an increase in cardiovascular risk (CVR) in women with polycystic ovary syndrome (PCOS), considered primarily as the result of the combination of all the clinical features that characterize the syndrome, including hyperandrogenism, insulin resistance, diabetes, obesity chronic low-grade inflammation. Interestingly, in 2012 it has been proposed the so-called DOGMA theory, suggesting the pivotal role played by microbiota alteration in the development of PCOS. Subsequently, several authors evidenced the existence in PCOS women of a marked dysbiosis, which is related to the development of metabolic diseases and cardiovascular complications, mainly due to the production of bacteria-derived metabolites that interfere with various pathways. Among these, trimethylamine-N-oxide (TMAO) is emerging as one of the most important and studied microbiota-derived metabolites related to the increase in CVR, due to its pro-atherosclerotic effect. The purpose of the present review is to summarize the evidence in order to support the hypothesis that, in women with PCOS, dysbiosis might be further involved in enhancement of the CVR via contributing to the increase of circulating TMAO. Although no observational studies on a large number of patients directly investigated the serum levels of TMAO in PCOS women, this manuscript aimed to drive future studies in this field, concurring in providing a novel approach for both comprehension and treatment of the CVR in PCOS.
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Affiliation(s)
- Giuseppe Annunziata
- NutraPharmaLabs, Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
| | - Roberto Ciampaglia
- NutraPharmaLabs, Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
| | - Xavier Capò
- Research Group in Community Nutrition and Oxidative Stress and Health Research Institute of the Balearic Islands (IdISBa), University of Balearic Islands-IUNICS, E-07122 Palma de Mallorca, Spain.
| | - Fabrizia Guerra
- NutraPharmaLabs, Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
| | - Antoni Sureda
- Research Group in Community Nutrition and Oxidative Stress and Health Research Institute of the Balearic Islands (IdISBa), University of Balearic Islands-IUNICS, E-07122 Palma de Mallorca, Spain; CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Gian Carlo Tenore
- NutraPharmaLabs, Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
| | - Ettore Novellino
- NGN Healthcare - New Generation Nutraceuticals s.r.l., Torrette Via Nazionale 207, 83013 Mercogliano, Avellino, Italy.
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37
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Li X, Cheng W, Shang H, Wei H, Deng C. The Interplay between Androgen and Gut Microbiota: Is There a Microbiota-Gut-Testis Axis. Reprod Sci 2021; 29:1674-1684. [PMID: 34037957 DOI: 10.1007/s43032-021-00624-0] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 05/13/2021] [Indexed: 12/12/2022]
Abstract
The gut microbiota, a large ecosystem interacting with the host, has been shown to affect the health and fitness of the host-microbial superorganism. Increasing evidence suggests that the gut microbiota communicates with distal organs of the host including the brain, liver, and muscle, as well as testis, through various complex mechanisms. So far, we know that the androgen can markedly remodel the gut microbiota and has initiated an interdisciplinary field termed "microgenderome." More recently, the gut microbiota has been found as a major regulator of androgen production and metabolism in turn and even could trespass the blood-testis barrier (BTB) to regulate spermatogenesis, which largely updates the current knowledge on male reproduction. In this review, we provided a brief overview of the context of the gender bias of diseases related to gut microbiota, the sex dimorphism of gut microbiota, and their relationships with androgen. We also summarized the known interaction between the testis and gut microbiota based on published animal studies and tentatively discussed the hypothesis of microbiota-gut-testis axis. Finally, we highlighted the opportunities and challenges underlying the ongoing research. This knowledge may extend our understanding of the role of gut microbiota in male health and microbiota-related diseases.
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Affiliation(s)
- Xiangping Li
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Wei Cheng
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Haitao Shang
- Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Hong Wei
- Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Chunhua Deng
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
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38
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Beauruelle C, Guilloux CA, Lamoureux C, Héry-Arnaud G. The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases. Front Med (Lausanne) 2021; 8:600879. [PMID: 34026772 PMCID: PMC8137850 DOI: 10.3389/fmed.2021.600879] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 04/12/2021] [Indexed: 12/13/2022] Open
Abstract
The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal “microgenderome” has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.
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Affiliation(s)
- Clémence Beauruelle
- Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.,Unité de Bactériologie, Pôle de Biologie-Pathologie, Centre Hospitalier Régional et Universitaire de Brest, Hôpital de la Cavale Blanche, Brest, France
| | | | - Claudie Lamoureux
- Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.,Unité de Bactériologie, Pôle de Biologie-Pathologie, Centre Hospitalier Régional et Universitaire de Brest, Hôpital de la Cavale Blanche, Brest, France
| | - Geneviève Héry-Arnaud
- Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.,Unité de Bactériologie, Pôle de Biologie-Pathologie, Centre Hospitalier Régional et Universitaire de Brest, Hôpital de la Cavale Blanche, Brest, France
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Ganci M, Butt H, Tyrrell J, Suleyman E, Ball M. The effect of Blastocystis sp. and Dientamoeba fragilis on psychological symptom severity in a sample of clinically diverse males and females. CURRENT PSYCHOLOGY 2021. [DOI: 10.1007/s12144-021-01700-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AbstractHealth outcomes associated with Blastocystis sp. and Dientamoeba fragilis are disparate and controversial, ranging from health benefits, to years of asymptomatic carriage, through to severe illness. Evidence that Blastocystis sp. and D. fragilis are commensal members of the gut microbiota is growing. Despite this, little to no research exists investigating the potential effect of these protozoa on psychological symptom expression. As such, the aim of this retrospective cross-sectional study was to be the first to investigate the effect of protozoan carriage on severity of Depressive, Neurocognitive, Stress and Anxiety, and Sleep and Fatigue symptoms, and whether this effect changes as a function of sex. The prevalence of D. fragilis was significantly higher in females compared to males, however there were no sex differences in prevalence for Blastocystis sp. (data used in the current study contained ST1, ST3, and Blastocystis ST unspecified) or co-carriage of the two. Females reported significantly more severe symptoms across all four psychological domains compared to males. There was no significant interaction between sex and Blastocystis sp. carriage on psychological symptom severity, and no significant main effect of Blastocystis sp. on symptom severity compared to those who tested negative for protozoa. When investigating the sexes separately, there was no effect of protozoan carriage on psychological symptom expression in either males or females. These findings add weight to the argument that Blastocystis sp. and D. fragilis are not necessarily pathogenic and are likely to be part of a diverse gut (which is typically associated with better health outcomes). Further research is required given that protozoan members of the gut microbiota have been largely ignored in brain-gut-microbiota axis research.
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40
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Skowron K, Bauza-Kaszewska J, Kraszewska Z, Wiktorczyk-Kapischke N, Grudlewska-Buda K, Kwiecińska-Piróg J, Wałecka-Zacharska E, Radtke L, Gospodarek-Komkowska E. Human Skin Microbiome: Impact of Intrinsic and Extrinsic Factors on Skin Microbiota. Microorganisms 2021; 9:543. [PMID: 33808031 PMCID: PMC7998121 DOI: 10.3390/microorganisms9030543] [Citation(s) in RCA: 134] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
The skin is the largest organ of the human body and it protects the body from the external environment. It has become the topic of interest of researchers from various scientific fields. Microorganisms ensure the proper functioning of the skin. Of great importance, are the mutual relations between such microorganisms and their responses to environmental impacts, as dysbiosis may contribute to serious skin diseases. Molecular methods, used for microorganism identification, allow us to gain a better understanding of the skin microbiome. The presented article contains the latest reports on the skin microbiota in health and disease. The review discusses the relationship between a properly functioning microbiome and the body's immune system, as well as the impact of internal and external factors on the human skin microbiome.
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Affiliation(s)
- Krzysztof Skowron
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
| | - Justyna Bauza-Kaszewska
- Department of Microbiology and Food Technology, UTP University of Science and Technology, 85-029 Bydgoszcz, Poland;
| | - Zuzanna Kraszewska
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
| | - Natalia Wiktorczyk-Kapischke
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
| | - Katarzyna Grudlewska-Buda
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
| | - Joanna Kwiecińska-Piróg
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
| | - Ewa Wałecka-Zacharska
- Department of Food Hygiene and Consumer Health, Wrocław University of Environmental and Life Sciences, 31 C.K. Norwida St., 50-375 Wrocław, Poland;
| | - Laura Radtke
- Faculty of Civil and Environmental Engineering and Architecture, UTP University of Science and Technology in Bydgoszcz, Al. prof. S. Kaliskiego 7, 85-796 Bydgoszcz, Poland;
| | - Eugenia Gospodarek-Komkowska
- Department of Microbiology, Nicolaus Copernicus University in Toruń, L. Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (Z.K.); (N.W.-K.); (K.G.-B.); (J.K.-P.); (E.G.-K.)
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41
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Hernandez AR, Banerjee A, Carter CS, Buford TW. Angiotensin (1-7) Expressing Probiotic as a Potential Treatment for Dementia. FRONTIERS IN AGING 2021; 2:629164. [PMID: 34901930 PMCID: PMC8663799 DOI: 10.3389/fragi.2021.629164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 03/05/2021] [Indexed: 12/12/2022]
Abstract
Increasing life expectancies are unfortunately accompanied by increased prevalence of Alzheimer's disease (AD). Regrettably, there are no current therapeutic options capable of preventing or treating AD. We review here data indicating that AD is accompanied by gut dysbiosis and impaired renin angiotensin system (RAS) function. Therefore, we propose the potential utility of an intervention targeting both the gut microbiome and RAS as both are heavily involved in proper CNS function. One potential approach which our group is currently exploring is the use of genetically-modified probiotics (GMPs) to deliver therapeutic compounds. In this review, we specifically highlight the potential utility of utilizing a GMP to deliver Angiotensin (1-7), a beneficial component of the renin-angiotensin system with relevant functions in circulation as well as locally in the gut and brain.
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Affiliation(s)
- Abbi R. Hernandez
- Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Anisha Banerjee
- Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Christy S. Carter
- Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL, United States
- Nathan Shock Center, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Thomas W. Buford
- Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL, United States
- Nathan Shock Center, University of Alabama at Birmingham, Birmingham, AL, United States
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42
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Huang J, Shan W, Li F, Wang Z, Cheng J, Lu F, Guo E, Beejadhursing R, Xiao R, Liu C, Yang B, Li X, Fu Y, Xi L, Wang S, Ma D, Chen G, Sun C. Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice. Aging (Albany NY) 2021; 13:7589-7607. [PMID: 33658399 PMCID: PMC7993734 DOI: 10.18632/aging.202627] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 11/10/2020] [Indexed: 11/25/2022]
Abstract
Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks’ old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.
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Affiliation(s)
- Jia Huang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Wanying Shan
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Fuxia Li
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Zizhuo Wang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Jing Cheng
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People's Republic of China
| | - Funian Lu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ensong Guo
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Rajluxmee Beejadhursing
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Rourou Xiao
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Chen Liu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Bin Yang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Xi Li
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Yu Fu
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ling Xi
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Shixuan Wang
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Ding Ma
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Gang Chen
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
| | - Chaoyang Sun
- Cancer Biology Research Center, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.,Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
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Watanabe S, Kameoka S, Shinozaki NO, Kubo R, Nishida A, Kuriyama M, Takeda AK. A cross-sectional analysis from the Mykinso Cohort Study: establishing reference ranges for Japanese gut microbial indices. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2021; 40:123-134. [PMID: 33996369 PMCID: PMC8099632 DOI: 10.12938/bmfh.2020-038] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 01/17/2021] [Indexed: 12/18/2022]
Abstract
The purpose of this study was to establish reference ranges for gut microbial indices by collecting real-world Japanese microbiome data from a Mykinso cohort. Although several large cohort studies have focused on the human gut microbiome, large cohort studies of the gut microbiome from Japanese populations are scarce, especially from healthy or non-diseased individuals. We collected stool samples and original survey lifestyle information from 5,843 Japanese individuals through the Mykinso gut microbiome testing service. From the obtained 16S rRNA sequence data derived from stool samples, the ratio and distribution of each taxon were analyzed. The relationship between different epidemiological attributes and gut microbial indicators were statistically analyzed. The qualitative and quantitative indicators of these common gut microbiota were confirmed to be strongly correlated with age, sex, constipation/diarrhea, and history of lifestyle-related diseases. Therefore, we set up a healthy sub-cohort that controlled for these attribute factors and defined reference ranges from the distribution of gut microbial index in that population. Taken together, these results show that the gut microbiota of Japanese people had high beta-diversity, with no single "typical" gut microbiota type. We believe that the reference ranges for the gut microbial indices obtained in this study can be new reference values for determining the balance and health of the gut microbiota of an individual. In the future, it is necessary to clarify the clinical validity of these reference values by comparing them with a clinical disease cohort.
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Affiliation(s)
| | | | | | - Ryuichi Kubo
- Cykinso, Inc., 1-36-1 Yoyogi, Shibuya, Tokyo 151-0053, Japan
| | - Akifumi Nishida
- Cykinso, Inc., 1-36-1 Yoyogi, Shibuya, Tokyo 151-0053, Japan.,Department of Electrical Engineering and Bioscience, Waseda University, 1-104 Totsuka, Shinjuku-ku, Tokyo 169-8050, Japan.,School of Computing, Tokyo Institute of Technology, 2-12-1 Okayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Minoru Kuriyama
- Cykinso, Inc., 1-36-1 Yoyogi, Shibuya, Tokyo 151-0053, Japan
| | - Aya K Takeda
- Cykinso, Inc., 1-36-1 Yoyogi, Shibuya, Tokyo 151-0053, Japan
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44
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Whon TW, Kim HS, Shin N, Jung ES, Tak EJ, Sung H, Jung M, Jeong Y, Hyun D, Kim PS, Jang YK, Lee CH, Bae J. Male castration increases adiposity via small intestinal microbial alterations. EMBO Rep 2021; 22:e50663. [PMID: 33225575 PMCID: PMC7788444 DOI: 10.15252/embr.202050663] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 10/20/2020] [Accepted: 10/22/2020] [Indexed: 01/21/2023] Open
Abstract
Castration of young males is widely used in the cattle industry to improve meat quality, but the mechanism linking hypogonadism and host metabolism is not clear. Here, we use metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. After pubescence, the CtM cattle harbor distinct ileal microbiota dominated by the family Peptostreptococcaceae and exhibit distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. We also evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. Castration of male mice phenocopies both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model confirm that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Collectively, targeting the gut microbiota is a potential therapeutic strategy for the treatment of both hypogonadism and obesity.
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Affiliation(s)
- Tae Woong Whon
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
- Present address:
Microbiology and Functionality Research GroupWorld Institute of KimchiGwangjuKorea
| | - Hyun Sik Kim
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Na‐Ri Shin
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
- Present address:
Biological Resource CenterKorea Research Institute of Bioscience and BiotechnologyJeongeup‐si, Jeollabuk‐doKorea
| | - Eun Sung Jung
- Department of Bioscience and BiotechnologyKonkuk UniversitySeoulKorea
| | - Euon Jung Tak
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Hojun Sung
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Mi‐Ja Jung
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Yun‐Seok Jeong
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Dong‐Wook Hyun
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Pil Soo Kim
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
| | - Yu Kyung Jang
- Department of Bioscience and BiotechnologyKonkuk UniversitySeoulKorea
| | - Choong Hwan Lee
- Department of Bioscience and BiotechnologyKonkuk UniversitySeoulKorea
| | - Jin‐Woo Bae
- Department of Life and Nanopharmaceutical Sciences and Department of BiologyKyung Hee UniversitySeoulKorea
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45
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Pace F, Watnick PI. The Interplay of Sex Steroids, the Immune Response, and the Intestinal Microbiota. Trends Microbiol 2020; 29:849-859. [PMID: 33257138 DOI: 10.1016/j.tim.2020.11.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 11/01/2020] [Accepted: 11/03/2020] [Indexed: 12/11/2022]
Abstract
The role of sex steroids in mammalian maturation is well established. Recently, it has been increasingly appreciated that sex steroids also play an important role in the propensity of adults to develop a myriad of diseases. The exposure and responsiveness of tissues to sex steroids varies among individuals and between the sexes, and this has been correlated with gender-specific differences in the composition of the intestinal microbiota and in susceptibility to metabolic, autoimmune, and neoplastic diseases. Here we focus on recent studies that demonstrate an interplay between sex steroids, the intestinal immune response, and the intestinal microbiota. While correlations between biological sex, the intestinal innate immune response, intestinal inflammation, and intestinal microbiota have been established, many gaps in our knowledge prevent the emergence of an overarching model for this complex interaction. Such a model could aid in the development of prebiotic, probiotic, or synthetic therapeutics that decrease the risk of autoimmune, metabolic, neoplastic, and infectious diseases of the intestine and mitigate the particular health risks faced by individuals receiving sex steroid treatment.
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Affiliation(s)
- Fernanda Pace
- Division of Infectious Diseases, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
| | - Paula I Watnick
- Division of Infectious Diseases, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
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46
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Ishida S, Kato K, Tanaka M, Odamaki T, Kubo R, Mitsuyama E, Xiao JZ, Yamaguchi R, Uematsu S, Imoto S, Miyano S. Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota. Commun Biol 2020; 3:686. [PMID: 33208821 PMCID: PMC7674416 DOI: 10.1038/s42003-020-01416-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 10/21/2020] [Indexed: 12/22/2022] Open
Abstract
Numerous host extrinsic and intrinsic factors affect the gut microbiota composition, but their cumulative effects do not sufficiently explain the variation in the microbiota, suggesting contributions of missing factors. The Japanese population possesses homogeneous genetic features suitable for genome-wide association study (GWAS). Here, we performed GWASs for human gut microbiota using 1068 healthy Japanese adults. To precisely evaluate genetic effects, we corrected for the impacts of numerous host extrinsic and demographic factors by introducing them as covariates, enabling us to discover five loci significantly associated with microbiome diversity measures: HS3ST4, C2CD2, 2p16.1, 10p15.1, and 18q12.2. Nevertheless, these five variants explain only a small fraction of the variation in the gut microbiota. We subsequently investigated the heritability of each of the 21 core genera and found that the abundances of six genera are heritable. We propose that the gut microbiota composition is affected by a highly polygenic architecture rather than several strongly associated variants in the Japanese population.
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Affiliation(s)
| | - Kumiko Kato
- Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | | | | | | | | | | | - Rui Yamaguchi
- Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoshi Uematsu
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka, Japan
- Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoru Miyano
- Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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47
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Pretorius L, Smith C. The trace aminergic system: a gender-sensitive therapeutic target for IBS? J Biomed Sci 2020; 27:95. [PMID: 32981524 PMCID: PMC7520957 DOI: 10.1186/s12929-020-00688-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/15/2020] [Indexed: 02/06/2023] Open
Abstract
Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a "missing link" that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.
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Affiliation(s)
- Lesha Pretorius
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1, Stellenbosch, 7062, South Africa
| | - Carine Smith
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1, Stellenbosch, 7062, South Africa.
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48
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Gadi N, Wu SC, Spihlman AP, Moulton VR. What's Sex Got to Do With COVID-19? Gender-Based Differences in the Host Immune Response to Coronaviruses. Front Immunol 2020; 11:2147. [PMID: 32983176 PMCID: PMC7485092 DOI: 10.3389/fimmu.2020.02147] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/07/2020] [Indexed: 01/08/2023] Open
Abstract
The novel severe acute respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has ravaged the world, with over 22 million total cases and over 770,000 deaths worldwide as of August 18, 2020. While the elderly are most severely affected, implicating an age bias, a striking factor in the demographics of this deadly disease is the gender bias, with higher numbers of cases, greater disease severity, and higher death rates among men than women across the lifespan. While pre-existing comorbidities and social, behavioral, and lifestyle factors contribute to this bias, biological factors underlying the host immune response may be crucial contributors. Women mount stronger immune responses to infections and vaccinations and outlive men. Sex-based biological factors underlying the immune response are therefore important determinants of susceptibility to infections, disease outcomes, and mortality. Despite this, gender is a profoundly understudied and often overlooked variable in research related to the immune response and infectious diseases, and it is largely ignored in drug and vaccine clinical trials. Understanding these factors will not only help better understand the pathogenesis of COVID-19, but it will also guide the design of effective therapies and vaccine strategies for gender-based personalized medicine. This review focuses on sex-based differences in genes, sex hormones, and the microbiome underlying the host immune response and their relevance to infections with a focus on coronaviruses.
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Affiliation(s)
- Nirupa Gadi
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- School of Medicine, Boston University, Boston, MA, United States
| | - Samantha C. Wu
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- School of Medicine, Boston University, Boston, MA, United States
| | - Allison P. Spihlman
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- School of Medicine, Boston University, Boston, MA, United States
| | - Vaishali R. Moulton
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
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Mohammadi SO, Yadegar A, Kargar M, Mirjalali H, Kafilzadeh F. The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis. J Diabetes Metab Disord 2020; 19:1855-1861. [PMID: 33553045 DOI: 10.1007/s40200-020-00608-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 08/05/2020] [Indexed: 12/12/2022]
Abstract
The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.
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Affiliation(s)
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Kargar
- Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshid Kafilzadeh
- Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
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Abstract
Vertebrates synthesize a diverse set of steroids and bile acids that undergo bacterial biotransformations. The endocrine literature has principally focused on the biochemistry and molecular biology of host synthesis and tissue-specific metabolism of steroids. Host-associated microbiota possess a coevolved set of steroid and bile acid modifying enzymes that match the majority of host peripheral biotransformations in addition to unique capabilities. The set of host-associated microbial genes encoding enzymes involved in steroid transformations is known as the sterolbiome. This review focuses on the current knowledge of the sterolbiome as well as its importance in medicine and agriculture.
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