Search Results (2,341)

Emerging evidence highlights the gut microbiota as a critical modulator in the pathogenesis of heart failure (HF), particularly among patients with type 2 diabetes mellitus (T2DM). Dysbiosis contributes to systemic inflammation, endothelial dysfunction, and adverse cardiac remodeling via microbial metabolites such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs). However, the therapeutic intersection between the gut microbiota and pharmacological interventions remains insufficiently integrated. Sodium-glucose cotransporter-2 inhibitors (SGLT2is), a cornerstone of T2DM management, confer cardioprotective effects that may involve microbiota-mediated pathways. This review provides a novel synthesis of how SGLT2is influence gut ecology, specifically through altered glucose excretion and osmotic shifts, to potentially restore SCFA-producing taxa. By delineating the structural transitions from gut physiology to SGLT2i-modulated cardiac outcomes, we emphasize the gut–heart axis as a pivotal therapeutic target. This focused framework offers new insights into the triadic interplay between microbiome stability and cardiometabolic health, moving beyond traditional glucose-centric paradigms. Full article

Background/Objectives: Bile acids, synthesized from cholesterol in the liver, are amphipathic molecules that play an integral role in lipid digestion and absorption, while also serving as systemic endocrine hormones. They continuously undergo enterohepatic circulation, where they interact with various transporter proteins. Dysregulated bile acid transport is associated with the pathogenesis of liver disease. This review summarizes the key findings relating to bile acid transport expression and activity in the pathogenesis of liver disease. Methods: A review of the literature was performed using PubMed and relevant terms including, but not limited to, “bile acid transporters”, “liver disease”, and “bile acid uptake and efflux”. Studies published in peer-reviewed journals relevant to this review were considered and reviewed. Results: Within the gut and liver, several key bile acid and xenobiotic transporters within the enterohepatic circulation are dysregulated. The directionality and extent of changes are cell- and disease-specific. Many of the regulatory processes are driven by changes in bile acid signaling, although further work is needed to expand on post-translational modification of bile acid transporters in liver disease. Conclusions: Bile acid transporters are dynamically regulated in liver diseases with distinct etiologies. Therefore, restoring BA transporter function represents an actionable therapeutic approach to liver disease. Full article

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host–microbiome interactions in modulating neuro-immune functions via gut–brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut–brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe–metabolite networks allied to gut–brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut–brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders. Full article

A comparative chemical analysis was conducted between P. aibuhitensis of orange and green body colors, evaluating their proximate composition, fatty acid profile, amino acid profile, astaxanthin content, lipidomic profile, and other biochemical parameters. Samples were categorized by body color into two groups, each with ten biological replicates. The samples were collected from the same local polychaete farm. The results revealed that the green phenotype had significantly higher moisture content but lower crude protein, crude lipid, and ash content compared to the orange phenotype. The orange polychaete was characterized by significantly higher concentrations of 16:0 and saturated fatty acids (SFAs), whereas the green one exhibited higher contents of n-6 polyunsaturated fatty acids (n-6 PUFAs) and a higher PUFA/SFA ratio. Regarding free amino acids, the orange polychaete had significantly higher threonine content, while the green ones had significantly higher levels of valine, isoleucine, leucine, phenylalanine, glutamate, alanine, histidine and proline. Additionally, the astaxanthin content was significantly higher in the orange phenotype. The bile acid level was significantly higher in the green phenotype compared to the orange one, but no significant differences were observed in other biochemical parameters such as total protein, total cholesterol, and triglyceride content. The lipidomic analysis revealed that glycerophospholipids were the most abundant lipid class in both phenotypes, followed by glycerolipids and sphingolipids. A total of 65 differentially abundant lipid molecules were identified between the two groups. Compared to the orange polychaete, the green one had higher levels of 59 lipids (predominantly ceramides) and lower levels of six lipids, including three triglycerides, one monogalactosyldiacylglycerol, and two phosphatidylserines. In general, the orange P. aibuhitensis showed a favorable nutritional profile for aquafeed and human nutrition, whereas the green ones had potential for targeted health applications owing to its specific lipid composition. However, direct validating experiments are required. Full article

In modern intensive mutton sheep farming, the high cost and limited supply of conventional feed resources necessitate the exploration of sustainable alternatives. Cotton stalks and sugar beet pulp, abundant agricultural by-products in China, have potential as ruminant feed after proper fermentation treatment, yet their systematic application in sheep production remains underinvestigated. This study evaluated the effects of replacing whole-plant corn microsilage with mixed fermented feed (cotton stalks and sugar beet pulp, 1:1 dry matter ratio) on Suffolk rams (n = 84, 4 months old). Animals were randomly assigned to four groups: control (CK, 0% replacement), MS30 (30% replacement), MS60 (60% replacement), and MS90 (90% replacement). After a 15-day adaptation, the 120-day feeding trial assessed growth performance, slaughter characteristics, meat quality, muscle metabolomics (LC-MS), and jejunal microbiota (16S rRNA sequencing). The MS60 group significantly outperformed the CK group in final body weight, carcass weight, and net weight gain (p < 0.01), slaughter rate (p < 0.05), and meat tenderness (p < 0.05). Fatty acid composition was optimized, with lower SFAs (p < 0.01) and higher MUFAs (p < 0.01). Metabolomic analysis revealed 206 differentially abundant metabolites, with significant enrichment in linoleic acid metabolism, unsaturated fatty acid biosynthesis, and primary bile acid synthesis pathways. The MS60 group exhibited significantly altered jejunal microbiota structure (p < 0.05), including increased Patescibacteria abundance (p < 0.05) and decreased Bifidobacterium (p < 0.001). Replacing 60% of whole-plant corn microsilage with cotton stalk–beet pulp mixed microsilage effectively improved production performance, meat quality, and fatty acid profiles in Suffolk rams, while modulating muscle metabolism and intestinal microbiota structure. These findings provide a practical strategy for sustainable sheep farming utilizing regional agricultural by-products. Full article

A bacterial strain M4 exhibiting high nattokinase (NK) activity and favorable antibacterial properties was isolated from fermented soybean paste in Northeast China. Based on morphological observation, physiological and biochemical characterization, 16S rDNA sequence analysis, and whole-genome sequencing, the strain was identified as Bacillus velezensis. Its probiotic potential and safety were systematically evaluated using a combination of in vitro assays and genome mining. Genomic analysis revealed that M4 possessed a complete genome consisting of a single circular chromosome of 4,473,838 bp with a GC content of 46.94%, encoding 4516 predicted proteins. Functional domain annotation identified four proteins (XLQ58132.1, XLQ58158.1, XLQ59409.1, and XLQ59873.1) containing both the Peptidase inhibitor I9 and Peptidase S8 domains, confirming the presence of the typical molecular signature of NK. Furthermore, the genome harbored 132 genes encoding carbohydrate-active enzymes, 37 biosynthetic gene clusters, and 142 genes encoding proteolytic enzymes. Comparative genomic analysis revealed a close phylogenetic relationship with other B. velezensis strains and identified 98 strain-specific genes. Safety assessment demonstrated that M4 exhibited no hemolytic activity, was susceptible to eight commonly tested antibiotics, and lacked genes encoding high-risk virulence factors. Probiotic characterization indicated that M4 exhibited certain levels of gastrointestinal tolerance, acid resistance, bile salt resistance, antioxidant activity, and antibacterial properties. In conclusion, B. velezensis M4 shows potential for development as a functional strain. Full article

Background and Objectives: Drug-induced liver injury (DILI) is increasingly associated with the use of herbal medicines. Ephedra sinica (ES) occasionally induces hepatocellular injury, yet therapeutic strategies for herb-induced liver injury are limited. This study investigated the potential mechanisms of a multicomponent pharmacopuncture formulation (VP) in ES-associated hepatotoxicity. Materials and Methods: Bioactive constituents of VP were collected from pharmacological databases and literature. The physicochemical properties were evaluated using SwissADME. Compound–target interactions were identified using the STITCH database and integrated with DILI–related genes retrieved from GeneCards (relevance score ≥ 5.0). Protein–protein interaction network analysis, Gene Ontology enrichment, and KEGG pathway analyses were performed. Results: A total of 22 overlapping targets were identified. A nine-gene module—comprising TNF, IL6, STAT3, CASP3, PINK1, PRKN, NFE2L2, HMOX1, and ABCB11—was associated with key biological processes, including inflammatory signaling, mitochondrial quality control, oxidative stress regulation, and hepatobiliary transport. Conclusions: These findings suggest that VP may modulate multiple biological processes relevant to hepatotoxic stress, including inflammatory signaling, mitochondrial quality control, and bile acid transport. These results provide a plausible mechanistic framework for further investigation, pending experimental validation. Full article

Ulcerative colitis (UC) is a type of inflammatory bowel disease without curative therapeutics. Recent studies demonstrate that Akkermansia muciniphila exerts mitigating effects on UC, but the underlying mechanisms remain unclear. In this study, we isolated a strain of A. muciniphila, designated NND9, from the feces of DSS-induced ulcerative colitis model mice and investigated its effects on UC of the mouse model. NND9 significantly alleviated UC severity in the mice by restoring gut barrier integrity through improving colonic mucus layer thickness, mitigating goblet cell depletion, and halting epithelial cell death. Mechanistically, NND9 suppressed the expression of the Tnfrsf10b gene encoding death receptor 5 (DR5) on the surface of colonic epithelial cells. Additionally, NND9 inhibited the phosphorylation of kinase 3 (RIPK3) and the pseudokinase mixed-lineage kinase domain-like protein (MLKL) associated with the necrotic apoptosis pathway, thereby reducing gut epithelial cell death. NND9 also markedly ameliorated the gut microbiome of the colitis mice. Untargeted metabolomics analysis demonstrated that NND9 modulated both tryptophan and bile acid metabolism. In conclusion, NND9 exhibits curative effects on UC by resolving inflammatory reactions of the gut mucosa through the DR5-RIPK3/p-RIPK3-MLKL/p-MLKL pathway and redressing gut dysbiosis. This study provides valuable information for the development of innovative therapeutic strategies for the treatment of UC. Full article

This study aimed to investigate the effects of dietary bile acids (BA) supplementation on serum antioxidant capacity, fecal fermentation characteristics, microbial diversity, and community composition in culled ewes. Twenty 5-year-old culled Hu ewes with similar body weights (42.95 ± 1.07 kg) were randomly allocated to two groups (n = 10 per group). The control group (CON) received a basal diet, while the treatment group (BA400) was fed the same basal diet supplemented with 400 mg/kg BA. Compared with the CON group, the BA400 group showed enhanced serum activities of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase, while also showing reduced concentrations of cortisol, malondialdehyde, and reactive oxygen species (p < 0.05). Fecal pH, ammonia nitrogen, total volatile fatty acids, and the concentrations and proportions of individual volatile fatty acids remained unaffected by BA supplementation (p > 0.05). Microbial analysis revealed that the BA400 group exhibited higher fecal bacterial richness and diversity than the CON group (p < 0.05). Analysis of similarities revealed significant differences between the CON and BA400 groups (R = 1.000, p = 0.007). Specifically, BA supplementation increased the relative abundances of beneficial taxa, including Verrucomicrobiota and Akkermansia, while decreasing potentially pathogenic bacteria such as Campylobacterota and Proteobacteria. These findings indicate that dietary BA supplementation improves serum antioxidant capacity and modulates fecal microbial diversity and community structure in culled ewes, suggesting that hindgut microbiota may contribute to the health benefits of BA supplementation in ruminant production. Full article

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies. Full article

Quorum Quenching (QQ) is a mechanism that disrupts Quorum Sensing (QS) signaling systems, which regulate gene expression based on bacterial population density. Many fish pathogens, such as Aeromonas, utilize QS systems to regulate the expression of their virulence factors. Disrupting these systems using QQ is a promising approach for infection control in aquaculture and may provide a safe alternative to antibiotics. Therefore, identifying microorganisms with QQ activity is a relevant task in agricultural microbiology and veterinary medicine. This study examines the identification of isolates with QQ activity in the microbial community of perch and assesses their probiotic potential for the prevention of aeromonosis. In this study, we isolated 32 strains of microorganisms capable of degrading N-acylhomoserine lactone (AHL), six of which exhibited stable QQ activity. Five strains were found to belong to the genus Rhodococcus, and one strain to the genus Exiguobacterium. The selected strains were tested for the enzymatic/non-enzymatic and intra-/extracellular QQ activity, pathogen growth inhibition, biofilm formation, and hemolytic activity, as well as growth ability under various environmental conditions (salinity, pH, bile acids, and temperature). Based on the results of these tests, the R. erythropolis PFS1.20 strain was selected as the most promising probiotic. The genomic analysis revealed that the studied strain contains genes encoding QQ enzymes, siderophore biosynthesis clusters, osmoprotectors, and compounds with antimicrobial properties. These results indicate the high probiotic potential of the R. erythropolis PFS1.20. Full article

The gut microbiota plays a multifaceted role in calcium homeostasis and bone metabolism —acting through metabolic, immunological, and hormonal pathways that collectively constitute the gut–bone axis. The microbiota influences calcium bioavailability through several overlapping mechanisms that act in the intestine. Moreover, microbial fermentation products may directly impact the osteoblast–osteoclast interplay and, by modulating immune and endocrine functions, are crucial for bone metabolism. A healthy microbiota supports bone formation; however, intestinal dysbiosis may impair bone structure and function. This narrative review aims to present pathways linking the gut microbiota to bone metabolism, both in health and disease. First, we will discuss the influence of gut microbiota on calcium absorption. We will then outline the role that microbial metabolites, such as bile acids and short-chain fatty acids (SCFAs), play in regulating bone structure and function. In the following section, we will discuss the role of the microbiota in the immunological and hormonal modulation of bone metabolism. Finally, we will discuss how dysbiosis affects bone and how therapeutic interventions, such as probiotics, prebiotics, and postbiotics, may influence bone tissue quality. Full article

Albendazole (ABZ) exhibits poor oral absorption; therefore, ABZ was conjugated to cholic acid to engage the apical sodium-dependent bile acid transporter (ASBT) and promote ileal uptake. ABZ–linker–CA conjugates bearing amino-alcohol linkers (C4–C8) were evaluated by integrating synthetic feasibility, purification selectivity, and ex vivo performance. Thermal aminolysis in DMF (95 °C) produced ABZ–linkers in ~50% reaction yields (HPLC-assayed), with a minor ABZ-amine by-product consistent with a workup-sensitive isocyanate route. Immobilized-lipase screening identified Lipozyme RM IM as the most effective catalyst for CA esterification in CHCl₃, showing a pronounced linker-length dependence (31% yield for C4, 25% for C6, and C8 ≤ 2.6% yield). Docking and molecular dynamics supported this trend by indicating productive binding geometries for C4/C6 but not for C8. A polarity-guided workup and silica-gel protocol enabled retrieval of unreacted intermediates and CA recycling, with cleaner separation for the C6 series. Ex vivo transport studies confirmed ASBT-mediated, linerixibat-sensitive ileal uptake, and protoscolex assays showed improved antiparasitic efficacy versus ABZ. Overall, ABZ-C6-CA offered the best balance of uptake, near-maximal efficacy, enzymatic accessibility, and separability, supporting its prioritization for scalable biocatalytic manufacturing. Full article

Objective: This study aimed to evaluate maternal serum afamin levels in women with intrahepatic cholestasis of pregnancy (ICP), examine their relationship with fasting bile acid concentrations, and assess their association with perinatal outcomes. Methods: This prospective case-–control study included 80 singleton pregnancies followed at a tertiary perinatology center between October 2025 and March 2026. Forty women with ICP, defined by pruritus and fasting bile acids > 10 μmol/L, were compared with 40 healthy pregnant controls. Women with ICP were further stratified according to fasting bile acid levels as <40 and ≥40 μmol/L. Maternal serum afamin concentrations were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Maternal characteristics, liver biochemistry, fetal biometric and Doppler parameters as well as obstetric and neonatal outcomes were compared. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of afamin for ICP, and logistic regression analysis was used to assess its association with ICP. Results: Baseline maternal characteristics were comparable between groups. Maternal serum afamin levels were significantly higher in the ICP group than in controls (6.18 ± 4.24 vs. 3.98 ± 1.95 ng/mL, p = 0.004). Afamin correlated positively with fasting bile acids (r = 0.372, p = 0.018), but not with transaminases, gestational age at delivery, birth weight, or neonatal outcomes. In logistic regression, afamin was independently associated with ICP (adjusted odds ratio [aOR] 1.260; 95% confidence interval [CI] 1.059–1.500; p = 0.009). ROC analysis showed poor discrimination for ICP (area under the curve [AUC] 0.634, 95% CI 0.51–0.76, p = 0.039), whereas afamin did not discriminate between subgroups defined by fasting bile acid levels (<40 vs. ≥40 μmol/L). The optimal cut-off value of 4.93 ng/mL predicted ICP with 55% sensitivity, 67.5% specificity, a positive likelihood ratio of 1.69, and a negative likelihood ratio of 0.67. Conclusions: Maternal serum afamin levels are elevated in ICP and show a modest association with fasting bile acid burden. Its discriminatory performance is limited, and it does not reliably distinguish patients defined by a ≥40 μmol/L threshold. These findings suggest that afamin reflects the maternal response to cholestasis rather than disease severity and may serve as a complementary biomarker. Full article

The sodium-taurocholate cotransporting polypeptide (NTCP) plays a critical dual role in liver function: maintaining bile acid (BA) enterohepatic circulation and acting as a receptor for the entry of hepatitis B and D viruses into hepatocytes. This review outlines the impact of various post-translational modifications (PTMs) of NTCP—including phosphorylation, oligomerization, ubiquitination, and glycosylation—on its dynamic regulatory network. These modifications coordinate the modulation of NTCP’s membrane localization, stability, conformational state, and protein interactions, precisely controlling its functions in BA uptake and viral invasion. Targeting this PTM network presents a promising strategy for next-generation therapies that selectively inhibit viral infection while preserving BA transport, overcoming the limitations of conventional inhibitors that indiscriminately disrupt virus–NTCP interactions. By synthesizing recent insights into NTCP PTM research, this article highlights its role as a central regulator of its bifunctional properties and reveals potential avenues for precision therapies in viral hepatitis, cholestasis, and related liver diseases. However, most existing evidence is derived from in vitro or cell-based models, whereas in vivo studies and clinical validation remain limited; thus, the translational feasibility of strategies targeting post-translational modifications of NTCP still requires further investigation. Full article