Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization
Summary: Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cockta...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223012075 |
| _version_ | 1827895480215928832 |
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| author | Jian-Quan Luo Huan Ren Man-Yun Chen Qing Zhao Nian Yang Qian Liu Yong-Chao Gao Hong-Hao Zhou Wei-Hua Huang Wei Zhang |
| author_facet | Jian-Quan Luo Huan Ren Man-Yun Chen Qing Zhao Nian Yang Qian Liu Yong-Chao Gao Hong-Hao Zhou Wei-Hua Huang Wei Zhang |
| author_sort | Jian-Quan Luo |
| collection | DOAJ |
| description | Summary: Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder. |
| first_indexed | 2024-03-12T22:22:30Z |
| format | Article |
| id | doaj.art-34cdc8a52e0847f4b9d1d061f2c6cec3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:30Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-34cdc8a52e0847f4b9d1d061f2c6cec32023-07-23T04:55:39ZengElsevieriScience2589-00422023-07-01267107130Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarizationJian-Quan Luo0Huan Ren1Man-Yun Chen2Qing Zhao3Nian Yang4Qian Liu5Yong-Chao Gao6Hong-Hao Zhou7Wei-Hua Huang8Wei Zhang9Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Department of Pharmacy, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, No.61 Western Jiefang Road, Changsha, Hunan, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Corresponding authorDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Corresponding authorSummary: Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.http://www.sciencedirect.com/science/article/pii/S2589004223012075Biological sciencesMolecular physiologyImmunologyCell biology |
| spellingShingle | Jian-Quan Luo Huan Ren Man-Yun Chen Qing Zhao Nian Yang Qian Liu Yong-Chao Gao Hong-Hao Zhou Wei-Hua Huang Wei Zhang Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization iScience Biological sciences Molecular physiology Immunology Cell biology |
| title | Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization |
| title_full | Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization |
| title_fullStr | Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization |
| title_full_unstemmed | Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization |
| title_short | Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization |
| title_sort | hydrochlorothiazide induced glucose metabolism disorder is mediated by the gut microbiota via lps tlr4 related macrophage polarization |
| topic | Biological sciences Molecular physiology Immunology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223012075 |
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