Tudcabil (tauroursodeoxycholic acid) / Bruschettini - LARVOL DELTA

Late Breaking Abstract - Gut microbiota-derived tauroursodeoxycholic acid attenuates sepsis-induced coagulopathy through platelet TGR5 (ERS 2026) - "Conclusions SIC features depleted bile acid-producing microbes, impaired secondary bile acid metabolism, and TUDCA deficiency. Microbiome-derived TUDCA restricts thrombosis and platelet activation via platelet TGR5, validating the microbiota-bile acid-platelet axis as a therapeutic target."

Gut Microbiota • Late-breaking abstract • Cardiovascular • Hematological Disorders • Infectious Disease • Septic Shock • Thrombocytopenia • Thrombosis

Towards extended preservation of human livers during long-term normothermic machine perfusion: The role of bile acids (TTS 2026) - "Bile acid dysregulation may contribute to the development of a toxic hepatobiliary environment and cholestatic injury, which is an important consideration for graft dysfunction in LT-NMP. TCA supplementation alone does not appear sufficient to ameliorate cholestasis. Instead, supplementation with TUDCA might represent a promising strategy to better stimulate bile flow to prevent accumulation of potentially toxic bile acids."

Cholestasis • Hepatology

Postelectroacupuncture Fecal Microbiota Transplantation (post-EA FMT) Regulates Gastrointestinal Hormones in Functional Dyspepsia Rats Is Associated With Modulation of the Intestinal Microbiota-Bile Acid Metabolic Pathway. (PubMed, J Gastroenterol Hepatol) - "The gut microbiota-BA pathway associates with post-EA FMT's beneficial regulation of gastrointestinal hormones. The gut microbiota-BA pathway is associated with post-EA FMT's beneficial regulation of gastrointestinal hormones. The gut microbiota-BA pathway is associated with post-EA FMT's beneficial regulation of gastrointestinal hormones. The Lactobacillus/TUDCA/TCDCA axis represents a candidate pathway that may contribute to this process (validation pending). Current findings indicate strong correlations, not causality."

Journal • Preclinical • Dyspepsia • Transplantation

Cancer-associated fibroblasts drive immune resistance in MSS colorectal cancer via the FAIM2-CES1-ER stress pathway. (PubMed, Mol Cell Biochem) - "Conversely, FAIM2 knockdown enhances ER stress and collagen synthesis, which are mitigated by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA)...In vivo, FAIM2 overexpression restrains tumor growth, reduces collagen deposition, and promotes tertiary lymphoid structure (TLS) formation, whereas CES1 co-overexpression counteracts these effects. Together, these findings reveal a potential FAIM2-CES1-ER stress axis in CAFs associated with ECM remodeling and immune contexture in MSS CRC, providing a rationale for future studies exploring its therapeutic potential in immunotherapy."

IO biomarker • Journal • Colorectal Cancer • Fibrosis • Oncology • Solid Tumor • CAFs • CES1 • MMP2

Energy-sparing effect of oregano essential oil-lauric acid complex in broilers: Insights from serum metabolomics and 16S rRNA sequencing. (PubMed, Poult Sci) - "Key differential metabolites included elevated tauroursodeoxycholic acid and L‑threonine, and decreased taurodeoxycholic acid, argininosuccinate, adenine, and S‑methyl‑5'‑thioadenosine...PICRUSt2 functional prediction further indicated enhanced homolactic fermentation and short‑chain fatty acid synthesis pathways. Collectively, these findings suggest that OEL is associated with improved feed efficiency under energy restriction, which may be linked to a systematic remodeling of host amino acid, bile acid, and nucleotide metabolism, as well as a shift in gut microbiota composition toward butyrate‑producing bacteria and reduced opportunistic pathogens."

Journal

Akkermansia muciniphila alleviates osteoporosis by suppressing bone marrow adiposity through the gut microbiota-UDCA-TGR5 axis. (PubMed, Life Sci) - "Integrated untargeted metabolomics and targeted bile acid profiling revealed that AKK supplementation notably restored ursodeoxycholic acid (UDCA) levels in both serum and feces. Metagenomic analyses showed that AKK reshaped bile salt hydrolase (BSH)-related microbial functions, thereby promoting the intestinal deconjugation of tauroursodeoxycholic acid to generate UDCA...Collectively, our study reveals a novel mechanism underlying the anti-osteoporotic effects of AKK, whereby AKK suppresses pathological BMA expansion through the gut microbiota-UDCA-TGR5 signaling axis. These findings provide a potential therapeutic strategy for osteoporosis and bone marrow lipid metabolic dysfunction."

Journal • Metabolic Disorders • Obesity • Osteoporosis • Rheumatology • TGFB1 • TGFBR1

The Effect and Potential Pharmacological Mechanism of Tauroursodeoxycholic Acid for Spinal Cord Injury: A Systematic Review and Network Pharmacology. (PubMed, Curr Neuropharmacol) - "TUDCA can enhance neuronal autophagy and inhibit inflammatory factor expression, reducing inflammatory response and suppressing neuronal apoptosis in SCI. Due to the limited number and uneven quality of included studies, further laboratory studies and validation in clinical trials are necessary to clarify the neuroprotective effect of TUDCA."

Journal • CNS Disorders • Inflammation • Orthopedics • AKT1 • CDC37 • EGFR • HSP90AA1 • PPARG

Tazarotene-Induced Gene 2 Promotes Melanoma Cell Death via the Activation of Endoplasmic Reticulum Stress. (PubMed, Front Biosci (Landmark Ed)) - "These findings suggest that TIG2 suppresses melanoma cell growth by activating ER stress and modulating immune-related chemokines, highlighting its potential therapeutic relevance."

Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • CCL2 • CXCL10 • CXCL11 • DDIT3 • RARRES2

Uncovering strategies to rescue muscle mass in ageing. (PubMed, J Physiol) - No abstract available

Journal • Muscular Atrophy • Sarcopenia

Bacillus coagulans Improves Performance by Modulating Bile Acid Metabolism to Suppress Hepatic Lipid Accumulation and Attenuating Ovarian Oxidative Stress in Late Laying Hens. (PubMed, Animals (Basel)) - "Furthermore, Bacillus coagulans significantly increased the levels of the bile acids GCDCA, TUDCA, THDCA, LCA, and HDCA in the ileum (p < 0.05). Bacillus coagulans not only increased the activity of T-SOD and CAT in the ovaries, as well as the expression of the Nrf2, HO-1, and SOD1 genes (p < 0.05), but also increased the expression of the estrogen receptor ER-α, FSHR and LHR genes (p < 0.05). In conclusion, dietary supplementation with Bacillus coagulans improved production performance by regulating hepatic lipid metabolism and enhancing ovarian function in aged laying hens."

Journal • Metabolic Disorders • ER

TUDCA and 4-PBA in Preclinical Models of Beta-Cell Secretory Failure: A Systematic Review and Bayesian Meta-Analysis. (PubMed, Int J Mol Sci) - "Because no source report documents blinding of outcome assessment, the pooled estimate should be read as an upper bound. In conclusion, TUDCA and 4-PBA act as chemical chaperones that alleviate ER stress and may prevent terminal UPR activation and preserve the beta-cell exocytotic machinery, positioning them as candidate disease-modifying agents that merit confirmatory clinical evaluation."

Clinical • Journal • Preclinical • Retrospective data • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Rice Epiphytic Strain Enterococcus faecalis YMA3 Improves Corn Stover Silage Quality via Metabolic Regulation Without Shifting the Bacterial Community. (PubMed, Animals (Basel)) - "Metabolomic analysis identified 309 differential metabolites between YMA3-treated and control silage, including elevated phosphatidylcholine, tauroursodeoxycholic acid, and 3,4-dihydroxyphenylpropionic acid, along with enriched glycerophospholipid, amino acid, and fatty acid metabolism pathways-changes that may underpin improved preservation...Given the limitation that we tentatively annotated metabolites based on spectral matching rather than authentic standards, follow-up research needs to validate key differential metabolites and evaluate their feeding effects in animal trials. This work provides a preliminary foundation for developing novel microbial feed additives in ruminant production."

Journal

4-Phenylbutyrate Plus Wildtype GAT-1 Augmentation: A Dual Therapy to Rescue SLC6A1 Variant-Associated Developmental and Epileptic Encephalopathy. (PubMed, Genes (Basel)) - "Variant effects were evaluated by (i) protein-structure prediction across nine stability-prediction algorithms using the cryo-EM-derived human GAT-1 template (PDB 7Y7W); (ii) 3H-GABA uptake assays in HEK293T cells and in human iPSC-derived astrocytes and cortical neurons; (iii) live-cell confocal microscopy of ER colocalization; (iv) pharmacologic rescue with PBA, TUDCA and salubrinal (v) and GAT-1 cDNA gene-augmentation, alone and in combination with PBA. GAT-1 p.Ala305Val is a trafficking-impaired, loss-of-function variant whose dysfunction is amenable to two convergent therapeutic axes: pharmacologic correction of folding and trafficking, and augmentation of functional transporter expression. These findings support a two-pronged precision-medicine framework for SLC6A1-related DEEs in which PBA increased the transporter function augmented by genetic approaches."

Journal • CNS Disorders • Epilepsy • Gene Therapies

Two Standards-Aided LC-MS Technologies Uncover 30 "Unreported" Compounds in Natural Bear Bile Powder to Add a New Pharmacopoeia Quality-Marker. (PubMed, J Sep Sci) - "The new Q-marker was validated to be feasible by analysis of 11 batches of natural bear bile powder samples (B-5∼B-15), and the specific ratio of TCDCA/TUDCA (0.58∼0.98) can distinguish natural BBP from artificial BBP and other animal biles. All these findings not only lay a foundation for manufacturing technique improvement of artificial natural bear bile powder, but also promote pharmacopoeia to update the quality-control method."

Journal

Gut Microbiota-Immune Interactions in Chronic Lung Diseases: An Emerging Cross-Disease Perspective Gut-Lung Axis in Chronic Lung Disease. (PubMed, J Inflamm Res) - "We further summarise how SCFAs, tauroursodeoxycholic acid, tryptophan-derived indole metabolites and microbial fragments may regulate Th2 and Th17 inflammation, Th17/Treg balance, neutrophil function, epithelial barrier integrity and fibrotic remodelling...We also discuss unresolved issues, including animal-to-human translation and the difficulty of distinguishing gut-derived from airway-derived microbial signals. A more precise understanding of shared and disease-specific gut-lung circuits may support the rational development of mechanism-informed microbiota-targeted adjunctive strategies for chronic lung disease."

Journal • Review • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Fibrosis • Gastrointestinal Disorder • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • Transplantation

Causal link between polymyositis and idiopathic pulmonary fibrosis in individuals of European ancestry: A Mendelian randomization and multi-omics study identifying mediators and drug targets. (PubMed, Medicine (Baltimore)) - "Three drugs (butein, gambogic acid, tauroursodeoxycholic acid) showed strong binding affinity (ΔG < -7.0 kcal/mol)...Multi-omics revealed key mediating biomarkers and underlying biological pathways, while drug target prioritization identified 3 compounds with therapeutic potential. This informs prevention strategies."

Biomarker • Journal • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Myositis • Pulmonary Disease • Respiratory Diseases • CHCHD1 • CRABP2 • HSPA5 • TGFB1

Endoplasmic reticulum stress contributes to high-dose radiation-induced chronic mechanical and thermal neuropathic pain. (PubMed, Mol Pain) - "We discovered that endoplasmic reticulum (ER) stress was activated in the DRG, and intraperitoneal injections of the ER stress antagonists 4-phenylbutyric acid (4-PBA) and TUDCA significantly alleviated mechanical and thermal allodynia...Moreover, 4-PBA also ameliorated the motor dysfunction induced by high-dose radiation.InterpretationOur findings highlight the pivotal role of ER stress activation in the development of chronic neuropathic pain induced by high doses of radiation. Furthermore, our findings suggest that targeting ER stress may offer a promising approach for preventing chronic abnormal pain resulting from high doses of radiation."

Journal • Inflammation • Neuralgia • Pain • ATF3

Early-Life Exposure to InP/ZnS QDs Triggers Photoreceptor Apoptosis via ER Stress in Zebrafish: Implications for Nanomaterial-Induced Retinal Toxicity. (PubMed, Small) - "Moreover, TUDCA, an ER stress inhibitor, partially rescued the reduction in zebrafish ocular axial length and attenuated apoptosis in 661 W cells. In summary, this work identifies InP/ZnS QDs as potent developmental ocular toxicants that trigger ER stress-induced photoreceptor cell apoptosis following early-life exposure, and underscores the urgent need for nanomaterial-specific biosafety guidelines to mitigate delayed-onset visual impairment."

Journal • Ophthalmology

Lead triggers hepatocyte ferroptosis through coordinated mitochondrial injury and ER stress-mediated autophagic degradation of GPX4. (PubMed, Toxicology) - "Collectively, our findings reveal a novel hierarchical cascade, mitochondrial ROS-driven ER stress leading to autophagic degradation of GPX4, as a core mechanism of Pb-induced hepatic ferroptosis. Furthermore, TUDCA was identified as a potential therapeutic agent for Pb-induced hepatotoxicity."

Journal • Hepatology • Liver Failure • GPX4 • SLC7A11

Intermittent fasting in diabetic retinopathy: microbiome modulation, mechanisms, and clinical insights. (PubMed, Cardiovasc Endocrinol Metab) - "Simultaneously, intermittent fasting alters retinal gut microbial and bile metabolite responses and thus endorses a gut and eye relationship. These preclinical and emerging research insights thus project intermittent fasting and retinal therapies routed via intermittent fasting and bile acids modulation as retinal supportive and adjuvant therapies."

Journal • Review • Diabetic Retinopathy • Inflammation • Retinal Disorders

Hippocampal Endoplasmic Reticulum Stress Drives a Pro-inflammatory Microglial Bias and Neuroinflammation in Aged Mice with Perioperative Neurocognitive Disorder. (PubMed, Brain Res Bull) - "These findings support a mechanistic link between hippocampal ER stress and the pro-inflammatory microglia bias linked to postoperative neuroinflammation and cognitive impairment in aged mice."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Developmental Disorders • Inflammation • Musculoskeletal Diseases • Orthopedics • Psychiatry • ATF4 • ATF6 • CD86 • HSPA5 • MRC1

Repurposing glibenclamide for retinal protection: TUDCA-modified liposomes for ocular delivery. (PubMed, Int J Pharm) - "Notably, glibenclamide liposomes were also able to accumulate in the sclera, forming a reservoir for sustained release over time. Finally, the liposomal formulation demonstrated good tolerability in ARPE-19 cell lines, highlighting its potential as a safe and effective system for ocular delivery of glibenclamide."

Journal • Age-related Macular Degeneration • Diabetes • Diabetic Retinopathy • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus

Metabolic Profiling Reveals Organ-Specific Molecular Pathologies and Aging-Associated Biomarkers in Progeroid Laminopathy. (PubMed, Smart Med) - "Notably, we uncover disruption of a taurine-TCA-TUDCA cytoprotective axis, suggesting a coordinated metabolic vulnerability in PL...This overlap indicates a partial convergence between PL-associated and normal aging-related metabolic changes. Together, our findings provide a metabolic framework for understanding PL pathophysiology and highlight clinically accessible biomarkers that warrant future longitudinal validation."

Biomarker • Journal

ER stress-dependent Ddit4/REDD1 induction contributes to translational suppression during cisplatin-induced skeletal muscle atrophy. (PubMed, Chem Biol Interact) - "Using a mouse model and differentiated C2C12 myotubes, we examined ER stress signaling, protein synthesis, and mTORC1 activity following cisplatin treatment, and evaluated the effects of tauroursodeoxycholic acid (TUDCA), an ER stress-suppressing chemical chaperone. Furthermore, Ddit4/REDD1 knockdown partially restored protein synthesis and mTORC1 signaling. These findings indicate that cisplatin induces skeletal muscle atrophy via ER stress-associated translational suppression, at least partly through Ddit4/REDD1-mediated inhibition of mTORC1."

Journal • Cachexia • Muscular Atrophy • DDIT4

Genetic algorithm-guided sample design enables efficient machine learning-driven optimization of tauroursodeoxycholic acid production in engineered Escherichia coli. (PubMed, Bioresour Technol) - "ANN-based response surface analysis further revealed a biphasic effect of corn dextrin concentration on TUDCA conversion, indicating a nonlinear behavior that was not fully captured by quadratic regression models. This study provides a feasible and sample-efficient strategy for low-throughput fermentation optimization under constrained experimental resources."

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