Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders

Arief Gunawan Darmanto; Ting-Lin Yen; Jing-Shiun Jan; Tran Thanh Duy Linh; Rajeev Taliyan; Chih-Hao Yang; Joen-Rong Sheu

doi:10.1016/j.phrs.2024.107564

Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders

Pharmacol Res. 2024 Dec 27:211:107564. doi: 10.1016/j.phrs.2024.107564. Online ahead of print.

Authors

Arief Gunawan Darmanto¹, Ting-Lin Yen², Jing-Shiun Jan³, Tran Thanh Duy Linh⁴, Rajeev Taliyan⁵, Chih-Hao Yang⁶, Joen-Rong Sheu⁷

Affiliations

¹ Department 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, Indonesia.
² Department 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, ROC.
³ Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing St., Taipei 110, Taiwan, ROC.
⁴ Family Medicine Training Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Viet Nam.
⁵ Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani Campus, Pilani, Rajasthan, India.
⁶ 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. Electronic address: [email protected].
⁷ 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. Electronic address: [email protected].

PMID: 39733841
DOI: 10.1016/j.phrs.2024.107564

Abstract

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.

Keywords: Bile Acids; Gut-Brain Axis; Pharmacological Interventions; Psychiatric Disorders; TGR5 Receptor.

Publication types

Review