Urinary antimicrobials are associated with bile acid homeostasis and childhood obesity.

Efficient production of ursodeoxycholic acid via a deep eutectic solvent-enabled 7α- and 7β-hydroxysteroid dehydrogenase cascade system with enhanced solubility of 7-keto-lithocholic acid.

Non-alcoholic fatty liver disease (NAFLD) is a growing global health burden with limited therapeutic options. This study investigated the protective effects of mulberry leaf glutelin (UDG) on NAFLD using free fatty acid-induced HepG2 cells and a high-fat diet (HFD) mouse model. UDG inhibited pancreatic lipase and cholesterol esterase activities in vitro, promoted fecal lipid excretion, and reduced triglyceride and cholesterol accumulation in cells and liver tissue. In vivo, UDG administration significantly alleviated HFD-induced weight gain, dyslipidemia, hepatic steatosis, and liver injury (p < 0.05). Serum biochemical analyses showed improvements in ALT, AST, lipid profiles, and lipopolysaccharide levels, accompanied by decreased expression of inflammatory cytokines (IL-6, IL-1β, TNF-α) and suppression of the TLR4/MyD88/NF-κB signaling pathway. Furthermore, untargeted serum metabolomics revealed that UDG markedly regulated metabolic profiles, with enrichment in pathways related to bile acid metabolism, amino acid metabolism, and central carbon metabolism. Notably, metabolites such as cholic acid and chenodeoxycholic acid were negatively correlated with NAFLD indicators and restored by UDG intervention. These findings show that UDG exerts lipid-lowering, hepatoprotective, and anti-inflammatory effects against NAFLD, potentially through modulation of bile acid biosynthesis and serum metabolic pathways. This study highlights mulberry leaf glutelin as a promising plant protein source with functional food potential for NAFLD prevention and management.

α,ω-Hexadecanedioic acid induces proton-translocating decoupling at complex III via Q-cycle disruption: evidence from kinetic and structural analyses.

Lithocholic acid exerts antiviral activity against porcine epidemic diarrhea virus by enhancing TGR5-mediated type III interferon production.

Bile acid profile and white matter microstructural changes in early Alzheimer's disease.

The enzymatic degradation of bile acid-modified phospholipids by secretory phospholipase A2 (sPLA2) can induce membrane disruption in liposomes. However, the influence of bile acid hydrophilicity on this disruptive effect remains unclear. In this study, we synthesized four lipids by conjugating lithocholic acid (LCA: 3α-OH), chenodeoxycholic acid (CDCA: 3α-OH, 7α-OH) or its derivatives (7k-CDCA: 3α-OH, 7 = O; bk-CDCA: 3 = O, 7 = O) to a phosphocholine backbone. We found that sPLA2-mediated release of 6-carboxyfluorescein (6-CF) from liposomes was significantly faster with LCA-PC (100% release) than with the more hydrophilic CDCA-, 7k-CDCA-, or bk-CDCA-PC (14–30% release) in 2 hours. Assays of enzymatic degradation rates indicated that the low efficacy of CDCA-PC and 7k-CDCA-PC correlated with their slow hydrolysis by sPLA2. Although bk-CDCA-PC was degraded at a rate (13.01%) similar to LCA-PC (15.07%) in 2 hours, dialysis experiments revealed that its metabolite (bk-CDCA) readily diffused into the aqueous phase, unlike LCA, which remained anchored to the membrane. This demonstrates that the firm interfacial settlement of the bile acid metabolite is crucial for the membrane-disruptive effect. Our findings establish that increased hydrophilicity of the bile acid moiety attenuates the sPLA2-induced pore-forming effect, providing a critical guideline for the future design of sPLA2-responsive liposomal systems.

This study evaluates the therapeutic potential of enzymatically hydrolyzed wheat bran-derived zinc phytate (EEPZ) in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model, with chemically synthesized zinc phytate (ZnPA) and whole wheat bran (WHB) as controls. EEPZ modulated gut microbiota by increasing Lactobacillus vaginalis (0.15% to 18.6%) and reducing Desulfovibrio (5.19% to 1.29%). Metabolically, Lactobacillus vaginalis converted EEPZ or standard zinc phytate into bioavailable inositol phosphates (e.g., IP3, IP4, IP5) and ionic zinc in vitro and in vivo. Concomitantly, EEPZ altered short-chain fatty acid and bile acid profiles (Chenodeoxycholic acid increased by 30% and lithocholic acid increased by 80%). Mechanistically, EEPZ strengthened intestinal barrier integrity via HDAC3 and tight junction proteins (ZO-1, occludin) upregulation, while concurrently suppressing the PI3K/AKT/NF-κB signaling pathway. Collectively, EEPZ emerges as a novel, natural UC therapeutic candidate.

BackgroundType 2 diabetes mellitus (T2DM) is a chronic metabolic disease that poses a serious threat to health. Currently, there are no completely effective treatment options. Modulating intestinal flora and its metabolites may represent a promising new approach for diabetes therapy. Regulating intestinal microbiota and its metabolites through prebiotics, mediated by regulatory T (Treg) cells, could offer a novel strategy to improve the chronic inflammatory state associated with diabetes.ObjectiveThis study aimed to investigate the improvement of diabetes-related chronic inflammation by examining the effects of inulin (INU) and Lycium barbarum polysaccharides (LBP) in diabetic rats. This was achieved by modulating the bile acid metabolites of the intestinal flora through the FXR–FGF15–FGFR4 axis, thereby activating Treg cells in vivo and alleviating the inflammatory state associated with diabetes.MethodsA diabetic rat model was established using a high-fat diet and streptozotocin (STZ) injection. Sprague–Dawley rats were randomly allocated into four groups: type 2 diabetes mellitus (T2DM), T2DM with INU group (T2DM + INU), T2DM with LBP group (T2DM + LBP), and T2DM with INU and LBP group (T2DM + INU + LBP). After 8 weeks of intervention, the rats were euthanized, and relevant pathophysiological and biochemical indicators were analyzed.ResultsINU and LBP treatments significantly decreased the levels of inflammatory cytokines, including MCP-1, IL-18, NF-κB, NLRP3, superoxide dismutase (SOD), and malondialdehyde (MDA). Moreover, these alleviations of the inflammatory state of diabetes were partially attributed to the increased proportion of Treg cells. We found that the abundance of tauro β-muricholic acid (TβMCA) was reduced following INU and LBP treatment, whereas the relative abundances of chenodeoxycholic acid (CDCA), lithocholic acid (LCA), and hyocholic acid (HCA) were all increased compared to those in the untreated group. Mechanically, INU and LBP significantly influenced the negative feedback regulation of the FXR–FGF15–FGFR4 axis via intestinal bile acids, thereby increasing the proportion of Treg cells in the periphery of diabetic rats. Intriguingly, an increase in Treg cells after INU and LBP intervention was notably correlated with the improvement in the inflammatory state of diabetes.ConclusionsINU and LBP modulate bile acids derived from intestinal flora to improve the chronic inflammatory status of diabetic rats. Specifically, both exert their effectiveness by regulating gut microbial bile acid metabolites through the FXR–FGF15–FGFR4 axis to activate Treg cells. These findings provide an experimental basis for further exploration of the mechanism underlying the effects of this combination in diabetic animal models, which may contribute to clinical therapeutic practice for the control of the disease.

Eurotium cristatum (EC), a fungus derived from Fu brick tea, exhibits anti-obesity potential, but its mechanisms regulating intestinal gluconeogenesis (IGN) remain unclear. This study aimed to elucidate whether EC alleviates obesity and glucolipid metabolic disorders by modulating the gut microbiota and activating the IGN pathway. The 8-week EC administration at low (104 CFU/mL), medium (106 CFU/mL), and high doses (108 CFU/mL) ameliorated high-fat-diet (HFD)-induced metabolic abnormalities, including aberrant weight gain, dyslipidemia, glucose intolerance and hepatic injury with effects showing a dose-dependent trend. EC treatment significantly activated IGN, as indicated by increased colonic levels of short-chain fatty acids (SCFAs) and succinate (key IGN substrates) and the upregulation of IGN-key enzymes (PEPCK, FBPase, and G6Pase). In addition, EC treatment significantly alleviated the HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and enriching beneficial bacteria such as Lachnospiraece_NK4A136_group, Bacteroidota and Alloprevotella. Non-targeted metabolomics analysis revealed that EC significantly altered the linoleic acid metabolism, specifically decreasing the relative levels of bile acid and chenodeoxycholic acid (p < 0.01) while increasing those of linoleic acid and ricinoleic acid (p < 0.05). EC treatment reshaped the gut microbiome, promoted the production of beneficial metabolites (e.g., SCFAs), and consequently activated the IGN pathway, ultimately ameliorating host glucose and lipid metabolic disorders. Our findings provide mechanistic insights into the anti-obesity effects of EC, suggesting its potential for further investigation as a dietary intervention for metabolic diseases.

CGA combination consisting of Cordyceps sinensis polysaccharide, gypenosides, and amygdalin, is derived from Fuzheng Huayu capsule (a traditional Chinese medicine approved for liver fibrosis) via previous Uniform Design Experimentation. The effect of CGA on metabolic dysfunction-associated steatohepatitis (MASH) and the potential mechanism based on bile acids (BAs) alternative biosynthesis pathway-farnesoid X receptor (FXR) axis are investigated here. Alanine aminotransferase, hepatic triglyceride, malondialdehyde (MDA), BAs, fatty acids oxidation (FAO) activity, mRNA of inflammatory cytokines, α-smooth muscle actin (α-SMA), transforming growth factor-β, collagen type I, and FAO enzymes were detected. Liver sections underwent hematoxylin-eosin, Oil Red O, and Sirius red staining, and immunohistochemistry assay of F4/80 and α-SMA. Protein expression of peroxisome proliferator-activated receptor α (PPAR-α), FXR, BAs biosynthesis enzymes, small heterodimer partner (SHP), bile salt export pump (BSEP), adenosine triphosphate-binding cassette sub-family B member 4 (ABCB4) and nuclear factor-kappa B were detected. CGA ameliorated MASH, restoring FAO, PPAR-α, and FXR, accompanied by increased chenodeoxycholic acid proportion in the FXR agonist BAs pool, BAs alternative biosynthesis, and the FXR targets including SHP, BSEP, and ABCB4. CGA ameliorates MASH, promoting the hepatic BAs alternative biosynthesis pathway to activate FXR-PPARα restoring FAO.

Bile acids have many roles in biological systems, and they have received great attention recently. Bile from a cow, known as gall, together with garlic, wine, and leeks, is used in the traditional medicine recipe of Bald's Leechbook, a thousand-year-old Anglo-Saxon formula for the treatment of infected eyelash follicles. Different aspects of previous works on bile acids have been reported, and this work adds antiviral, virucidal, and antibacterial properties of bile acids and their salts against SARS-CoV-2. Four bile acids, lithocholic acid (LCA, 1), deoxycholic acid (DCA, 5), ursodeoxycholic acid (UDCA, 9), and chenodeoxycholic acid (CDCA, 13), were used to form salts with l-carnitine [X], creatinine [Y], and choline [Z], which are naturally occurring compounds. Bile acids and their salts were evaluated for antiviral and virucidal activities against SARS-CoV-2 as well as for their antibacterial properties. Among the bile acids tested, LCA (1) was found to display virucidal activity against SARS-CoV-2 with an EC50 of 9.69 µg mL−1 and a selectivity index (SI) of >5.16. However, its salts, [LCA][X] (2), [LCA][Y] (3), and [LCA][Z] (4), were 1.31–3.27 times less active than the bile acid LCA (1), indicating that salt forms of this bile acid did not have improved virucidal activity. Bile acids DCA (5), UDCA (9), and CDCA (13) exhibited antibacterial activity against Gram-positive bacteria (Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis) and against a Gram-negative bacterium (Escherichia coli). Cholinium salts of these bile acids exhibited enhanced antibacterial activity; for example, 41.4–41.5% antibacterial improvement was observed for the [DCA][Z] (8) salt when compared with its corresponding bile acid DCA (5). This work provides evidence that certain salts of bile acids have improved antibacterial activity, but they do not enhance antiviral properties.

Downregulation of hepatic sulfotransferase 1E1 expression associated with decreased expression of multidrug resistance-associated protein 2.

Understanding the interactions between gut microbiota, bile acid (BA) metabolism and systemic health is critical for supporting gestational physiological stability in sows, especially during the physiologically demanding late gestation period. Although physiological advantages vary by breed in late-gestation sows, the microbiota-related mechanisms underlying these differences remain poorly understood. This study compared serum antioxidant enzyme activity, oxidative damage markers, inflammatory cytokine levels, gut microbiota composition (analysed via 16S rRNA sequencing), and BA profiles (assessed through targeted metabolomics) between purebred large white (LW) and large white×landrace (LW×LR) crossbred sows during late gestation. Results showed that LW×LR crossbred sows exhibited significantly higher serum superoxide dismutase (SOD) activity and IL-10 levels, alongside reduced IL-6 levels (P<0.05), indicating enhanced antioxidant and anti-inflammatory capacity. Gut microbiota analysis revealed greater alpha diversity (Shannon indices) and a lower Simpson index, along with distinct beta diversity (P<0.05) in crossbred sows, with notable enrichment of functional taxa such as Treponema and Prevotella. Additionally, faecal concentrations of modified BAs, specifically 3-oxolithocholic acid and 7-ketolithocholic acid, were significantly elevated, correlating with increased abundance of gut microbiota encoding BA: Na+ symporter (BASS family) proteins, as well as the increased 7-α-hydroxysteroid dehydrogenase activity (P<0.05). In contrast, LW sows exhibited enrichment of Terrisporobacter and Clostridium sensu stricto 1, alongside accumulation of primary (e.g. chenodeoxycholic acid) and unconjugated BAs (e.g. deoxycholic acid) (P<0.05). Correlation analysis demonstrated that the accumulation of Terrisporobacter and primary BAs was positively correlated with exacerbation of inflammation. In conclusion, under intensive production conditions, significant differences in the gut microbiota-BA axis between LW and LW×LR crossbred sows may underlie variations in oxidative stress and inflammatory status during late pregnancy. These findings provide valuable insights into microbiome-BA-host associations underlying the physiological advantages (enhanced antioxidant and anti-inflammatory capacity) of crossbred sows.

The regulatory roles of pparα on hepatic drug-metabolizing enzymes in primary sclerosing cholangitis Syrian hamsters.

We previously reported that two bile acid (BA) analogs, CamSA and CA-Quin, demonstrate potent anti-germination activity against Clostridioides difficile (C. difficile) spores, protecting rodents from C. difficile infections. Here, we further evaluated the impact of these analogs on the hepatic transcriptome and BA homeostasis in vivo by focusing BA profiles on the liver, feces, and chyme as well as the hepatic transcriptome after a 7-day treatment. The two compounds demonstrated similar impact on BA profiles among the three samples, with significantly increased BA excretion in feces. This change is aligned with significantly altered expression of genes involved in BA homeostasis in both liver and gut tissues. Also, both compounds increased levels of deconjugated BAs in the feces, possibly suggesting increased activity of gut microbiota. Fecal levels of anti-C. difficile germination chenodeoxycholic acid and pro-germination taurocholic acid are significantly increased and decreased by the treatments, respectively. The hepatic transcriptome showed limited difference in gene expression between the three groups, suggesting a minimal adverse impact of the two compounds on liver function. Overall, our study suggests that in vivo CamSA and CA-Quin treatment demonstrated safe and significantly altered BA homeostasis that inhibits C. difficle germination.

Dietary chenodeoxycholic acid alleviates cottonseed oil-induced hepatic lipid deposition and inflammation in juvenile black seabream (Acanthopagrus schlegelii)

The effect of chenodeoxycholic acid inclusion in a plant-based diet on the crosstalk between gut microbiota and bile acids in tilapia

Purpose: The Amsterdam UMC pharmacy has been compounding chenodeoxycholic acid (CDCA) capsules for Dutch cerebrotendinous xanthomatosis patients since 2018. However, limited data are available on the pharmacokinetics and bioequivalence of therapeutic CDCA formulations. Methods: An open-label, single-center, randomized, two-period, two-sequence, cross-over study was conducted in 12 healthy volunteers to compare the pharmacokinetic profile of pharmacy-compounded CDCA capsules to that of the authorized CDCA product. Results: Both formulations reached peak plasma concentrations (tmax) at approximately 1 h post-dose. The mean AUC(0–6h) values were 262.4 (±69.4) µmol∙min/L for the compounded capsules and 248.0 (±78.1) µmol∙min/L for the authorized capsules, with a 90% confidence interval (CI) for the AUC(0–6h) ratio of 0.89–1.30, exceeding the accepted bioequivalence range of 0.80–1.25. The mean Cmax for the compounded formulation (2.96 ± 0.91 µmol/L) was significantly lower than that of the comparator product (4.42 ± 1.36 µmol/L; p = 0.0040), with a 90% CI for the Cmax ratio of 0.57–0.80, also outside the bioequivalence range. Conclusions: Overall, the pharmacy-compounded and authorized capsules demonstrate a comparable AUC(0–6h) and tmax. Bioequivalence could not be demonstrated, primarily due to high variation, a significantly lower Cmax, and an AUC(0–6h) ratio outside the accepted limits. These findings indicate that the compounded formulation results in reduced systemic peak exposure compared with the authorized product. However, given the high variation, a larger sample size would be needed to further investigate bioequivalence in future studies.

The disclosing of the full potential of aqueous Dye-SensitizedSolar Cells (a-DSSCs) is tightly bonded to the implementation of moresustainable, stable, and efficient electrolytes which are able toperform both in outdoor and indoor environments. In this contribution,we report the formulation of biopolymer-based hydrogels (e.g., chitosan,carrageenan, and porcine gelatin) in conjunction with ZnO nanoparticlesand their application as electrolytes in quasi-solid-state a-DSSC.The thorough characterization (XRD, IR, SEM) of the hydrogels revealstunable morphology impacting their ability to stabilize a I-basedredox mediator and chenodeoxycholic acid (CDCA) employed as an additive.Once implemented in a-DSSCs, all the biopolymer-based quasi-solidelectrolytes perform well, delivering a photoconversion efficiency(PCE) approaching or even overcoming 1% (comparable to the one ofa reference cell based on xanthan gum), showing an extremely highopen circuit voltage (>700 mV). The addition of CDCA, alternativelyduring the gel formulation or washing phase, enables the porcine gelatin-derivedsystems to increase their efficiency of about 50% and carrageenanones to ensure an extremely promising shelf life with any PCE decreaseover more than 15 days. More importantly, the porcine gelatin-derived,CDCA-additivated electrolytes are able to properly perform also underindoor light (i.e., 1200 lx), showing PCE values approaching 3% andoutperforming reference devices. Our results prove how a thoughtfulselection of the polymer scaffold and a specifically designed preparationstrategy are fundamental to improve the efficiency of sustainablequasi-solid aqueous electrolytes.