{"id":3467,"date":"2025-06-26T23:47:14","date_gmt":"2025-06-26T14:47:14","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3467"},"modified":"2025-06-26T23:47:15","modified_gmt":"2025-06-26T14:47:15","slug":"journal-club-2025-06-27","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3467","title":{"rendered":"Journal Club 2025.06.27"},"content":{"rendered":"\n<h2>A microbial amino-acid-conjugated bile acid,tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE<\/h2>\n\n\n\n<p class=\"has-text-align-left\"><strong>Jun\u00a0Lin\u00a0<sup>12318<\/sup>,\u00a0Qixing\u00a0Nie\u00a0<sup>12418<\/sup>,\u00a0Jie\u00a0Cheng\u00a0<sup>5618<\/sup>,\u00a0YaNi\u00a0Zhong\u00a0<sup>518<\/sup>,\u00a0Tianyao\u00a0Zhang\u00a0<sup>518<\/sup>,\u00a0Xiuying\u00a0Zhang\u00a0<sup>718<\/sup>,\u00a0Xiaoyan\u00a0Ge\u00a0<sup>618<\/sup>,\u00a0Yong\u00a0Ding\u00a0<sup>12318<\/sup>,\u00a0Canyang\u00a0Niu\u00a0<sup>58<\/sup>,\u00a0Yuhua\u00a0Gao\u00a0<sup>123<\/sup>,\u00a0Kai\u00a0Wang\u00a0<sup>123<\/sup>,\u00a0Mingxin\u00a0Gao\u00a0<sup>9<\/sup>,\u00a0Xuemei\u00a0Wang\u00a0<sup>123<\/sup>,\u00a0Weixuan\u00a0Chen\u00a0<sup>10<\/sup>,\u00a0Chuyu\u00a0Yun\u00a0<sup>10<\/sup>,\u00a0Chuan\u00a0Ye\u00a0<sup>123<\/sup>,\u00a0Jinkun\u00a0Xu\u00a0<sup>123<\/sup>,\u00a0Weike\u00a0Shaoyong\u00a0<sup>123<\/sup>,\u00a0Lijun\u00a0Zhang\u00a0<sup>9<\/sup>,\u00a0Pan\u00a0Shang\u00a0<sup>56<\/sup>,\u00a0Xi\u00a0Luo\u00a0<sup>123<\/sup>,\u00a0Zhiwei\u00a0Zhang\u00a0<sup>123<\/sup>,\u00a0Xin\u00a0Zheng\u00a0<sup>9<\/sup>,\u00a0Xueying\u00a0Sha\u00a0<sup>9<\/sup>,\u00a0Jinxin\u00a0Zhang\u00a0<sup>123<\/sup>,\u00a0Shaoping\u00a0Nie\u00a0<sup>4<\/sup>,\u00a0Xuguang\u00a0Zhang\u00a0<sup>11<\/sup>,\u00a0Fazheng\u00a0Ren\u00a0<sup>12<\/sup>,\u00a0Huiying\u00a0Liu\u00a0<sup>123<\/sup>,\u00a0Erdan\u00a0Dong\u00a0<sup>81314<\/sup>,\u00a0Xiao\u00a0Yu\u00a0<sup>9<\/sup>,\u00a0Linong\u00a0Ji\u00a0<sup>7<\/sup>,\u00a0Yanli\u00a0Pang\u00a0<sup>11516<\/sup>,\u00a0Jin-Peng\u00a0Sun\u00a0<sup>56<\/sup>,\u00a0Changtao\u00a0Jiang\u00a0<sup>1231719<\/sup><\/strong><\/p>\n\n\n\n<p><sup>1<\/sup>Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China<sup>2<\/sup>NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China<sup>3<\/sup>Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China<sup>4<\/sup>State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China<sup>5<\/sup>Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, China<sup>6<\/sup>Advanced Medical Research Institute, Meili Lake Translational Research Park, Cheeloo College of Medicine, Shandong University, Jinan, China<sup>7<\/sup>Department of Endocrinology and Metabolism, Peking University People\u2019s Hospital, Peking University Diabetes Centre, Beijing, China<sup>8<\/sup>Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China<sup>9<\/sup>Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China<sup>10<\/sup>Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China<sup>11<\/sup>Shanghai Institute of Nutrition and Health, The Chinese Academy of Sciences, Shanghai, China<sup>12<\/sup>Department of Nutrition and Health, Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, No. 10 Tianxiu Road, Haidian District, Beijing 100193, China<sup>13<\/sup>The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing, China<sup>14<\/sup>Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China<sup>15<\/sup>National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China<sup>16<\/sup>Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking University, Beijing, China<sup>17<\/sup>Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China<\/p>\n\n\n\n<p><strong>Received 25 February 2024, Revised 2 October 2024, Accepted 8 May 2025, Available online 29 May 2025.<\/strong><\/p>\n\n\n\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.cell.2025.05.010\">https:\/\/doi.org\/10.1016\/j.cell.2025.05.010<\/a><\/p>\n\n\n\n<h2>Highlights<\/h2>\n\n\n\n<ul>\n<li>Revealed microbiota-host interaction via microbial amino-acid-conjugated bile acids<\/li>\n\n\n\n<li>Trp-CA serves as the endogenous ligand of the orphan GPCR MRGPRE<\/li>\n\n\n\n<li>Identified a non-itch function of the itch family receptor MRGPRE in glucose control<\/li>\n\n\n\n<li>MRGPRE activation boosts GLP-1 secretion via the Gs-cAMP and \u03b2-arrestin-1-ALDOA pathways <\/li>\n<\/ul>\n\n\n\n<h2>Summary<\/h2>\n\n\n\n<p>Recently, microbial amino-acid-conjugated bile acids (MABAs) have been found to be prevalent in human samples. However, their physiological significance is still unclear. Here, we identify tryptophan-conjugated cholic acid (Trp-CA) as the most significantly decreased MABA in patients with type 2 diabetes (T2D), and its abundance is negatively correlated with clinical glycemic markers. We further demonstrate that Trp-CA improves glucose tolerance in diabetic mice. Mechanistically, we find that Trp-CA is a ligand of the orphan G protein-coupled receptor (GPCR) Mas-related G protein-coupled receptor family member E (MRGPRE) and determine the binding mode between the two. Both MRGPRE-Gs-cyclic AMP (cAMP) and MRGPRE-\u03b2-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits of Trp-CA. Additionally, we find that the bacterial bile salt hydrolase\/transferase of&nbsp;<em>Bifidobacterium<\/em>&nbsp;is responsible for the production of Trp-CA. Together, our findings pave the way for further research on MABAs and offer additional therapeutic targets for the treatment of T2D.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1.jpg\"><img decoding=\"async\" loading=\"lazy\" width=\"996\" height=\"996\" src=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1.jpg\" alt=\"\" class=\"wp-image-3469\" srcset=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1.jpg 996w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1-300x300.jpg 300w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1-150x150.jpg 150w, https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/Graphical-abstract-1-768x768.jpg 768w\" sizes=\"(max-width: 996px) 100vw, 996px\" \/><\/a><\/figure>\n\n\n\n<div class=\"wp-block-file\"><object class=\"wp-block-file__embed\" data=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/A-microbial-amino-acid-conjugated-bile-acid-tryptophan-cholic-acid-improves-glucose-homeostasis-via-the-orphan-receptor-MRGPRE.pdf\" type=\"application\/pdf\" style=\"width:100%;height:600px\" aria-label=\"Embed of A-microbial-amino-acid-conjugated-bile-acid-tryptophan-cholic-acid-improves-glucose-homeostasis-via-the-orphan-receptor-MRGPRE.\"><\/object><a id=\"wp-block-file--media-b68cb2eb-846e-4781-b3b9-f8d713dcb306\" href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/A-microbial-amino-acid-conjugated-bile-acid-tryptophan-cholic-acid-improves-glucose-homeostasis-via-the-orphan-receptor-MRGPRE.pdf\">A-microbial-amino-acid-conjugated-bile-acid-tryptophan-cholic-acid-improves-glucose-homeostasis-via-the-orphan-receptor-MRGPRE<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2025\/06\/A-microbial-amino-acid-conjugated-bile-acid-tryptophan-cholic-acid-improves-glucose-homeostasis-via-the-orphan-receptor-MRGPRE.pdf\" class=\"wp-block-file__button wp-element-button\" download aria-describedby=\"wp-block-file--media-b68cb2eb-846e-4781-b3b9-f8d713dcb306\">Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>A microbial amino-acid-conjugated bile acid,tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE Jun\u00a0Lin\u00a012318,\u00a0Qixing\u00a0Nie\u00a012418,\u00a0Jie\u00a0Cheng\u00a05618,\u00a0YaNi\u00a0Zhong\u00a0518,\u00a0Tianyao\u00a0Zhang\u00a0518,\u00a0Xiuying\u00a0Zhang\u00a0718,\u00a0Xiaoyan\u00a0Ge\u00a0618,\u00a0Yong\u00a0Ding\u00a012318,\u00a0Canyang\u00a0Niu\u00a058,\u00a0Yuhua\u00a0Gao\u00a0123,\u00a0Kai\u00a0Wang\u00a0123,\u00a0Mingxin\u00a0Gao\u00a09,\u00a0Xuemei\u00a0Wang\u00a0123,\u00a0Weixuan\u00a0Chen\u00a010,\u00a0Chuyu\u00a0Yun\u00a010,\u00a0Chuan\u00a0Ye\u00a0123,\u00a0Jinkun\u00a0Xu\u00a0123,\u00a0Weike\u00a0Shaoyong\u00a0123,\u00a0Lijun\u00a0Zhang\u00a09,\u00a0Pan\u00a0Shang\u00a056,\u00a0Xi\u00a0Luo\u00a0123,\u00a0Zhiwei\u00a0Zhang\u00a0123,\u00a0Xin\u00a0Zheng\u00a09,\u00a0Xueying\u00a0Sha\u00a09,\u00a0Jinxin\u00a0Zhang\u00a0123,\u00a0Shaoping\u00a0Nie\u00a04,\u00a0Xuguang\u00a0Zhang\u00a011,\u00a0Fazheng\u00a0Ren\u00a012,\u00a0Huiying\u00a0Liu\u00a0123,\u00a0Erdan\u00a0Dong\u00a081314,\u00a0Xiao\u00a0Yu\u00a09,\u00a0Linong\u00a0Ji\u00a07,\u00a0Yanli\u00a0Pang\u00a011516,\u00a0Jin-Peng\u00a0Sun\u00a056,\u00a0Changtao\u00a0Jiang\u00a01231719 1Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China2NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China3Department of Physiology and Pathophysiology, Center for [&hellip;]<\/p>\n","protected":false},"author":14,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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