Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders
Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing thei...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824005097 |
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| author | Arief Gunawan Darmanto Ting-Lin Yen Jing-Shiun Jan Tran Thanh Duy Linh Rajeev Taliyan Chih-Hao Yang Joen-Rong Sheu |
| author_facet | Arief Gunawan Darmanto Ting-Lin Yen Jing-Shiun Jan Tran Thanh Duy Linh Rajeev Taliyan Chih-Hao Yang Joen-Rong Sheu |
| author_sort | Arief Gunawan Darmanto |
| collection | DOAJ |
| description | Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders. |
| format | Article |
| id | doaj-art-cbb100f271984e2392889bf7e7f880ca |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-cbb100f271984e2392889bf7e7f880ca2025-01-09T06:13:07ZengElsevierPharmacological Research1096-11862025-01-01211107564Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disordersArief Gunawan Darmanto0Ting-Lin Yen1Jing-Shiun Jan2Tran Thanh Duy Linh3Rajeev Taliyan4Chih-Hao Yang5Joen-Rong Sheu6Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC; School of Medicine, Universitas Ciputra, Surabaya 60219, IndonesiaDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC; Department of Medical Research, Cathay General Hospital, Taipei 22174, Taiwan, ROCDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROCFamily Medicine Training Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Viet NamNeuropsychopharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani Campus, Pilani, Rajasthan, IndiaDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC; Research Center for Neuroscience, Taipei Medical University, Taipei, Taiwan, ROC; Corresponding author at: Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC.Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC; Research Center for Neuroscience, Taipei Medical University, Taipei, Taiwan, ROC; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, ROC; Corresponding author at: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, ROC.Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders.http://www.sciencedirect.com/science/article/pii/S1043661824005097Bile AcidsTGR5 ReceptorPsychiatric DisordersGut-Brain AxisPharmacological Interventions |
| spellingShingle | Arief Gunawan Darmanto Ting-Lin Yen Jing-Shiun Jan Tran Thanh Duy Linh Rajeev Taliyan Chih-Hao Yang Joen-Rong Sheu Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders Pharmacological Research Bile Acids TGR5 Receptor Psychiatric Disorders Gut-Brain Axis Pharmacological Interventions |
| title | Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders |
| title_full | Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders |
| title_fullStr | Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders |
| title_full_unstemmed | Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders |
| title_short | Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders |
| title_sort | beyond metabolic messengers bile acids and tgr5 as pharmacotherapeutic intervention for psychiatric disorders |
| topic | Bile Acids TGR5 Receptor Psychiatric Disorders Gut-Brain Axis Pharmacological Interventions |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824005097 |
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