Beyond Metabolic Messengers: Bile Acids and TGR5 as Pharmacotherapeutic Intervention for Psychiatric Disorders DOI Creative Commons

Arief Gunawan Darmanto,

Ting‐Lin Yen, Jing‐Shiun Jan

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107564 - 107564

Published: Dec. 1, 2024

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed current treatments. This review explores emerging role of bile acids TGR5 receptor in pathophysiology psychiatric conditions, emphasizing their signaling within gut-brain axis. We detail synthesis systemic functions acids, transformation gut microbiota, impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety schizophrenia, autism spectrum bipolar disorder. The highlights how dysbiosis altered acid metabolism contribute to development exacerbation these through mechanisms involving inflammation, oxidative stress, neurotransmitter dysregulation. Importantly, we both pharmacological non-pharmacological interventions that modulate signaling, offering potential breakthroughs treatment strategies. These include dietary adjustments enhance beneficial production use specific agonists have shown promise preclinical clinical settings for regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, neuroinflammation. By integrating findings from dynamics metabolism, related events, this underscores cutting-edge therapeutic approaches poised revolutionize management disorders.

Language: Английский

New insight into intestinal toxicity accelerated by aged microplastics with triclosan: inflammation regulation by gut microbiota-bile acid axis DOI

Dawu Lin,

Xiangyu Chen, Xiaojun Lin

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 492, P. 138308 - 138308

Published: April 15, 2025

Language: Английский

Citations

2
Microglia and Gut Microbiota: A Double-Edged Sword in Alzheimer's Disease DOI

Nargis Bano,

Sameera Khan,

Shakir Ahamad

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102515 - 102515

Published: Sept. 1, 2024

Language: Английский

Citations

9
The role of gut microbiota‐derived metabolites in neuroinflammation DOI Creative Commons

Lingjie Mu,

Yijie Wang

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Abstract Neuroinflammation, a key defense mechanism of the nervous system, is associated with changes in inflammatory markers and stimulation neuroimmune cells such as microglia astrocytes. Growing evidence indicates that gut microbiota its metabolites directly or indirectly regulate host health. According to recent studies, bacterial dysbiosis closely linked several central system disorders cause neuroinflammation, including multiple sclerosis, Alzheimer's disease, Parkinson's sepsis‐associated encephalopathy, ischemic stroke. Recent findings indicate bidirectional communication network between influences neuroinflammation cognitive function. Dysregulation this can affect generation cytotoxic metabolites, promote impair cognition. This review explores lesser‐studied microbiota‐derived involved neuroinflammation—bile acids, trimethylamine‐N‐oxide, indole derivatives—as targets for creating new treatment tools neuroinflammatory illnesses, well possible biomarkers early diagnosis prognosis.

Language: Английский

Citations

0
Aged Gut Microbiota Contributes to Cognitive Impairment and Hippocampal Synapse Loss in Mice DOI Creative Commons
Mingxiao Li, Yiyang Bao,

Jiaoqi Ren

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by early hallmark, hippocampal synaptic loss. However, impact and mechanistic role of gut in synapse loss remains unclear. Here, we observed that fecal naturally aged mice successfully transferred impairment to young recipients. Multi-omics analysis revealed was with obvious change Bifidobacterium pseudolongum (B.p) metabolite tryptophan, indoleacetic acid (IAA) periphery brain. These features were also reproduced recipients transplanted microbiota. Fecal B.p abundance reduced patients compared healthy subjects showed positive correlation scores. Microbiota transplantation from who had fewer abundances yielded worse behavior than those higher abundances. Meanwhile, supplementation capable producing IAA enhancing peripheral brain bioavailability, well improving behaviors microglia-mediated 5 × FAD transgenic mice. produced shown prevent microglia engulfment synapses an aryl hydrocarbon receptor-dependent manner. This study reveals -induced decline is, at least partially, due deficiency its metabolite, IAA. It provides proof-of-concept strategy preventing neurodegenerative diseases modulating probionts their tryptophan metabolites.

Language: Английский

Citations

0
Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility DOI Creative Commons
Haonan Zheng, Yuzhu Chen,

Siqi Lu

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 28, 2025

The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). mechanosensory Piezo2 has been implicated regulation function. However, it remains unclear whether is modulated by microbiota, thus contributing to development visceral hypersensitivity and dysmotility. study enrolled patients diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, colonoscopy mucosal biopsy were conducted. Fecal transplantation (FMT) was performed using samples from HC or IBS-D patients, interventions Akkermansia muciniphila Fusobacterium varium carried out on colon- dorsal root ganglion (DRG)- knockdown pseudo-germ-free mice. Visceral sensitivity motility assessed. levels detected western blot immunofluorescence. 16S rRNA sequencing cecum untargeted metabolomics analysis, followed molecular docking predictions Piezo2, also performed. ratio Piezo2+/5-HT+ cells lower positively correlated sensation dysbiosis. mice that received FMT exhibited colonic dysmotility hypersensitivity, along elevated protein colon DRG. Knockdown DRG ameliorated FMT-induced hypersensitivity. revealed distinct composition. Notably, varium, but not muciniphila, induced effects could be alleviated knockdown. Additionally, lead increased levels, as well indole-3-acetic acid indole-3-acrylic acid, which predicted bind causing disturbances. can regulated involved dysmotility, playing role.

Language: Английский

Citations

0
Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5 DOI Open Access

Xiulian Lin,

Li Xia, Yabo Zhou

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4240 - 4240

Published: April 29, 2025

Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), G protein-coupled bile acid (TGR5), play crucial roles in physiological pathological processes of cells. These receptors are involved regulation absorption, signal transduction, cellular proliferation repair, senescence, energy metabolism, modulation gut microbiota. A comprehensive literature search was conducted using PubMed, employing keywords such as acid, receptor, FXR (nr1h4), TGR5 (gpbar1), cells, proliferation, differentiation, microbiota, inflammatory bowel disease (IBD), colorectal cancer (CRC), irritable syndrome (IBS), with a focus on publications available English. This review examines diverse effects signaling pathways metabolism Additionally, it explores interactions between acids, well implications these for host health, particularly relation to prevalent diseases. Finally, highlights importance developing highly specific ligands context metabolic disorders.

Language: Английский

Citations

0
Young fecal microbiota transplantation improves working memory in aged recipient rats by increasing interleukin-4 and interleukin-17 levels DOI Creative Commons

Yiru Yin,

Mingzhu Guan, Shufen Wu

et al.

Neuroscience Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Gut microbiota and well-being: a comprehensive summary of the special issue DOI Creative Commons
Utpal Sen

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107791 - 107791

Published: May 1, 2025

Language: Английский

Citations

0
Beyond Metabolic Messengers: Bile Acids and TGR5 as Pharmacotherapeutic Intervention for Psychiatric Disorders DOI Creative Commons

Arief Gunawan Darmanto,

Ting‐Lin Yen, Jing‐Shiun Jan

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107564 - 107564

Published: Dec. 1, 2024

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed current treatments. This review explores emerging role of bile acids TGR5 receptor in pathophysiology psychiatric conditions, emphasizing their signaling within gut-brain axis. We detail synthesis systemic functions acids, transformation gut microbiota, impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety schizophrenia, autism spectrum bipolar disorder. The highlights how dysbiosis altered acid metabolism contribute to development exacerbation these through mechanisms involving inflammation, oxidative stress, neurotransmitter dysregulation. Importantly, we both pharmacological non-pharmacological interventions that modulate signaling, offering potential breakthroughs treatment strategies. These include dietary adjustments enhance beneficial production use specific agonists have shown promise preclinical clinical settings for regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, neuroinflammation. By integrating findings from dynamics metabolism, related events, this underscores cutting-edge therapeutic approaches poised revolutionize management disorders.

Language: Английский

Citations

1