Search Results (4,307)

Urban pigeons (Columba livia) are widely distributed synanthropic birds closely associated with environments of intense human activity, raising interest in their role in urban microbial dynamics. Here, we characterized the fecal bacterial microbiota of urban pigeons from northern Mexico using 16S rRNA gene amplicon sequencing (V3–V4). A total of 1479 amplicon sequence variants (ASVs) were identified across five pooled samples. Alpha diversity varied among pools, with observed richness ranging from 228 to 514 ASVs. The bacterial community was dominated by Proteobacteria and Firmicutes, particularly Escherichia–Shigella and Enterococcus. PICRUSt2-based functional predictions suggested a predominance of predicted metabolic pathways related to carbohydrate degradation and energy acquisition. Conservative taxonomic screening identified 58 gut-associated taxa, including 15 bacteria previously reported in association with humans; however, only three (Clostridium perfringens, Enterococcus faecalis, and Proteus mirabilis) showed reported zoonotic associations, all at very low relative abundances (<0.07%). These findings indicate that the fecal bacterial communities characterized in this study were dominated by taxa commonly associated with the avian gastrointestinal tract, whereas taxa that could be conservatively linked to documented zoonotic reports represented only a minor fraction of the detected microbiota. Overall, the results contribute to a more ecologically informed understanding of urban pigeon-associated microbiota within a One Health framework. Full article

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article

This narrative review examines perimenopause as a critical transitional phase in women’s lives, often accompanied by elevated vulnerability to anxiety and depression. Dysfunction of the gut–brain axis is one of the key factors contributing to perimenopausal mood disorders and is currently receiving extensive attention. GBA dysfunction can trigger neurotransmitter metabolic imbalance, intestinal barrier impairment, and neuroinflammatory responses. Tryptophan (Trp) and γ-aminobutyric acid (GABA) serve as essential precursors and direct modulators of key neurotransmitters, and the dysregulation of their metabolic pathways has been implicated in perimenopausal anxiety and depression in animal models and limited clinical observations. Trp influences 5-hydroxytryptamine (5-HT) by affecting emotional states. GABA is the primary inhibitory neurotransmitter in the central nervous system and is closely associated with anxiety and depression. Fluctuations in estrogen levels during perimenopause significantly alter the composition and metabolic activity of the gut microbiota, which in turn affects Trp metabolism and GABA synthesis through increased intestinal permeability, activation of immune-inflammatory responses, and disruption of hypothalamic–pituitary–adrenal (HPA) axis function. Although traditional hormone replacement therapy and pharmacological treatments are effective, they are associated with some side effects. Preliminary evidence from in vitro and animal studies suggests that nutritional interventions targeting Trp and GABA metabolism within the gut–brain axis may offer a novel research direction, though their efficacy in perimenopausal women remains to be established. Potential nutritional strategies, including supplementation with Trp and its precursors, inhibition of the kynurenine pathway (KP), and supplementation with probiotics and prebiotics, can modulate Trp and GABA metabolism. This review focuses on Trp and GABA metabolic regulation via the gut–brain axis to explore pathogenesis of perimenopausal anxiety and depression and summarize potential nutritional intervention targets, thereby providing a scientific basis for emotional management in perimenopausal women. Full article

This study investigated the metabolic regulatory effects and underlying microbial mechanisms of Deinococcus radiodurans extract (DRE), using high-fat diet (HFD)-induced obese mice as the primary mechanistic model and naturally overweight felines. In the mouse model, a 1.5% DRE supplementation mitigated HFD-induced obesity, reduced serum total cholesterol and low-density lipoprotein levels, and markedly ameliorated hepatic steatosis. Fecal 16S rRNA gene sequencing revealed that DRE effectively reversed murine microbial dysbiosis by significantly restoring core commensals depleted by the HFD, notably Ureaplasma and the short-chain fatty acid (SCFA)-producer Odoribacter, while concurrently suppressing the overgrowth of obesity-associated taxa including Alloprevotella and Phascolarctobacterium. As a translational complement, a 28-day DRE intervention in felines under isocaloric maintenance conditions, with no significant change in body weight, body condition score, or fecal score, validated these systemic benefits, significantly enhancing serum total antioxidant capacity by 16.1% and reducing the systemic inflammatory marker serum amyloid A by 27.8%, indicating that the antioxidant and anti-inflammatory effects of DRE are independent of weight change. Concurrently, feline fecal microbiota profiling demonstrated a parallel ecological remodeling, characterized by the enrichment of potent SCFA producers (Oscillibacter and the [Eubacterium]_hallii_group) and the profound suppression of the pro-inflammatory pathogen Fusobacterium. Collectively, by integrating deep mechanistic insights from mice with translational evidence from felines, this study demonstrates that DRE exerts comprehensive anti-obesity and anti-inflammatory effects by regulating lipid metabolism and reshaping the gut microbiota, establishing its robust potential as a novel functional ingredient for metabolic health in companion animals. Full article

This review evaluates multi-omics applications in dairy research across nutrition, safety, and health. Through multi-omics integration, we reveal nutrient differences driven by species, rearing practices, and processing techniques, identify protein patterns and allergen profiles, and construct adulteration detection fingerprints and species-specific peptide markers, thereby improving the timeliness and accuracy of safety assessment. The coupling of metagenomics and metabolomics effectively predicts spoilage-related microbial risks, enabling better risk control. Furthermore, multi-omics approaches systematically elucidate the functional mechanisms of bioactive peptides (e.g., ACE-inhibitory peptides), clarify the prebiotic effects of functional oligosaccharides, and build interaction networks between dairy components and gut microbiota. The introduction of machine learning enables origin and shelf-life prediction, as well as the discovery of novel biomarkers, promoting personalized nutrition and precision fermentation strategies. However, the field is currently constrained by severe reproducibility issues arising from the absence of standardized operating procedures, excessive optimism regarding machine learning models that rarely generalize across laboratories or product matrices, and a persistent disconnect between laboratory-scale biomarker discovery and industrial implementation. Without rigorous cross-platform validation and openly shared multi-omics reference datasets, most published markers remain unfit for regulatory or industrial application. Future efforts should establish standardized workflows and expand the evidence base to drive the dairy industry toward safer, healthier, and more traceable directions. Full article

Amphibian malformation syndromes significantly impact both conservation efforts and aquaculture, yet their underlying systemic pathophysiological mechanisms remain poorly characterized. This study comprehensively examines the multi-level pathological processes associated with the “short-leg” malformation syndrome in the black-spotted frog (Pelophylax nigromaculatus) using an integrated methodology, encompassing morphological, histopathological, gut microbiome, and hepatic transcriptomic analyses. Affected frogs demonstrated shortened limbs, impaired motor function, and a distinctive metabolic phenotype, including increased body weight despite a shorter body length, accumulation of visceral fat, and shortened intestines. Gut microbiota analysis identified significant compositional shifts, characterized by a decreased Firmicutes-to-Bacteroidota ratio, expansion of pro-inflammatory Proteobacteria, and reduction in beneficial Actinobacteriota, suggesting microbial niche restructuring that likely promotes metabolic and inflammatory disorders. Hepatic transcriptome profiling revealed 2617 differentially expressed genes, demonstrating a clear molecular dichotomy with concurrent up-regulation of immune-related pathways (e.g., neutrophil extracellular trap formation, complement cascades, and inflammatory signaling) and broad suppression of metabolic pathways (e.g., lipid oxidation, nutrient absorption, and PPAR and renin–angiotensin systems). This integrated analysis illustrates that the malformation syndrome represents a systemic pathophysiological state involving dysfunction of the gut–liver axis, characterized by the coexistence of gut microbiota alterations, hepatic metabolic suppression, and immune activation. These findings provide a framework for understanding amphibian malformations and suggest potential strategies to improve health outcomes in aquaculture. Full article

The aquatic plant Wolffia globosa and the probiotic Limosilactobacillus reuteri KUB-AC5 have been proposed as candidate synbiotic components targeting gut microbiota modulation. In this study, we investigated the effects of W. globosa supplementation, alone or in combination with L. reuteri KUB-AC5, on the gut microbiota and health status in healthy adult dogs. For a 28-day feeding trial, 24 healthy dogs were randomly assigned to three dietary treatment groups: control, prebiotic (PRE; 3.5% W. globosa powder), and synbiotic (SYN, 3.5% W. globosa powder combined with L. reuteri KUB-AC5 at 1 × 10⁸ CFU/day). No significant differences were observed in body weight, body condition score, fecal consistency, feed intake, or blood parameters among groups (p > 0.05). Although overall gut microbial diversity remained unchanged, linear discriminant analysis effect size analysis revealed the selective enrichment of specific bacterial taxa. The PRE group exhibited higher relative abundances of Parabacteroides merdae, Romboutsia lituseburensis, Subdoligranulum variabile, and Phocaeicola sartorii, whereas the SYN group showed increased levels of Escherichia coli and Terrisporobacter glycolicus and reduced levels of Anaerobiospirillum succiniciproducens and Campylobacter upsaliensis (p < 0.05). In conclusion, W. globosa, alone or combined with L. reuteri KUB-AC5, was safely used to modulate gut bacterial composition as a potential functional ingredient. Full article

The gut microbiome of rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) is increasingly recognized as a functional interface linking dietary inputs, epithelial barrier integrity, mucosal immunity, environmental stress, disease susceptibility, and antimicrobial-resistance risk in intensive aquaculture. Based on available salmonid studies and relevant evidence from broader fish and aquaculture systems, this review synthesizes current knowledge on salmonid gut microbial composition, nutritional modulation, microbiome–mucosal immune interactions, aquaculture stressors, antibiotic exposure, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), metagenomics, multi-omics, and emerging microbiome-informed decision-support tools. Current evidence does not support a universally stable single-core microbiota in these species. Instead, community structure is shaped by developmental stage, freshwater–seawater transition, intestinal segment, digesta versus mucosa sampling, diet, temperature, stress, health status, and methodological workflow. Feed substitution and functional additives can remodel the gut microbiota, but these shifts should be interpreted alongside histology, barrier function, metabolic profiles, immune indicators, and disease-resistance phenotypes. Antibiotic exposure may reduce acute bacterial disease pressure while disturbing community structure and potentially enriching ARGs or ARG–MGE associations. Risk assessment should therefore move beyond ARG abundance toward host–ARG–MGE linkage using shotgun metagenomics, metagenome-assembled genomes, long-read sequencing, Hi-C, and externally validated multi-omics models. Machine learning and artificial intelligence approaches may support feature screening, risk stratification, and decision support, but their application in salmonid gut-health management remains at an early stage and requires external validation across sites, production stages, diets, and seasons. Full article

Bacillus subtilis has been widely investigated as a probiotic feed additive for weanling piglets due to its potential to improve growth performance, gut health, and disease resilience during the post-weaning period. This systematic review evaluated the effects of Bacillus subtilis supplementation in pigs following PRISMA guidelines and the PICOS framework. A total of 619 records published between 2000 and 2025 were identified through PubMed, Scopus, and AGRICOLA databases, of which 29 studies met the inclusion criteria for qualitative synthesis. Overall, Bacillus subtilis supplementation frequently improved average daily gain, body weight, feed efficiency, and reduced diarrhea incidence, particularly under enteric challenge conditions. Many studies also reported beneficial effects on intestinal morphology, immune regulation, intestinal barrier-related gene expression, nutrient digestibility, and modulation of gut microbiota toward bacterial communities associated with intestinal health. However, responses varied depending on Bacillus subtilis strain, dosage, diet composition, and experimental design. In contrast, effects on biochemical and oxidative stress indicators were less consistent across studies. Collectively, the findings support the potential role of Bacillus subtilis as a functional probiotic in swine nutrition while highlighting the need for standardized long-term studies to better define optimal strains, supplementation strategies, and mechanisms of action. Full article

Ganoderma lucidum polysaccharide peptide (GLPP) is a food-derived macromolecule with immunomodulatory potential, but its gut-centered mechanisms under chemotherapy-associated immunosuppressive stress remain unclear. This study aimed to evaluate the protective effects of GLPP against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury in mice and to explore the associated microbiota–metabolite–gene interaction network using integrated foodomics. BALB/c mice were treated with CTX and then administered GLPP at 50, 100, or 200 mg/kg/day for 42 days, with levamisole as a positive control. High-dose GLPP restored spleen index from 1.592 ± 0.266 to 1.902 ± 0.212 mg/g and thymus index from 0.322 ± 0.146 to 0.656 ± 0.081 mg/g compared with the CTX group. It also enhanced lymphocyte proliferation (OD450: 1.529 ± 0.073 vs. 1.065 ± 0.051), increased carbon clearance index (3.403 ± 0.223 vs. 2.650 ± 0.164), elevated IL-2 and IgA levels, and reduced excessive IFN-γ and TNF-α responses. GLPP alleviated intestinal mucosal injury and reshaped gut microbial profiles, particularly taxa related to Bacteroidota and Bacteroides. Metabolomics revealed putatively annotated differential metabolites associated with amino acid, nicotinate–nicotinamide, and glycerophospholipid metabolism, while transcriptomics indicated modulation of PRR/MAPK-related immune signaling. Integrated correlation analysis suggested a microbiota–metabolite–gene–immune association network involving putative gamma-Glutamylleucine(γ-Glu-Leu), leukotriene D4(LTD4)-like lipid features, and hippuric acid. These findings support GLPP as a promising immune-supporting functional food ingredient, although metabolite assignments and causal mechanisms require further validation. Full article

Type 2 diabetes mellitus (T2DM) involves progressive muscle wasting, metabolic dysregulation in peripheral tissues, chronic hyperglycemia, and insulin resistance. Momordica charantia is an antidiabetic agent often limited by bitterness. To improve palatability and efficacy, we developed EMS by combining M. charantia and Stevia rebaudiana (9:1). EMS’s antidiabetic effects were tested in streptozotocin (STZ)-induced and genetic db/db mouse models of diabetes. Mice received oral EMS at doses (40, 80, and 120 mg/kg) for six weeks, assessing glucose tolerance, insulin sensitivity, lipid profile, and hepatic markers. Additionally, muscle protein synthesis and degradation mechanisms were analyzed in gastrocnemius tissues. EMS significantly reduced fasting blood glucose and improved insulin sensitivity in both models. EMS decreased liver lipid accumulation and serum ALT and AST levels, indicating hepatic protection. EMS alleviated muscle atrophy by increasing muscle fiber area and was associated with increased expression or activity of AMPK/Sirt1/PGC-1α and IRS-1/PI3K/AKT insulin pathways. It also suppressed FOXO3a-mediated expression of Atrogin-1 and MuRF1, suggesting reduced activation of protein-degradation pathways. Moreover, EMS modulated the gut microbiota, increasing the abundance of beneficial species such as Barnesiella intestinihominis. These findings suggest EMS is a promising multitarget functional ingredient for metabolic complications and musculoskeletal decline in T2DM. Full article

Background/Objectives: Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in the pathogenesis of ulcerative colitis (UC). Tryptophan metabolism and its interaction with the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2–related factor 2 (Nrf2) axis represent a crucial regulatory network in intestinal homeostasis. This study aimed to investigate whether the probiotic fermentation product postbiotic Nagqu4580 alleviates UC by modulating this network to inhibit intestinal epithelial ferroptosis. Methods: An acute UC model was induced in mice using 4% dextran sodium sulfate (DSS). The therapeutic effects of postbiotic Nagqu4580 were evaluated through disease activity index (DAI), colon length, histopathology, inflammatory cytokines, and intestinal barrier function. Ferroptosis was assessed by measuring lipid peroxidation (MDA, 4-HNE), antioxidant capacity (GSH/GSSG), and expression levels of GPX4 and ACSL4. Serum tryptophan metabolites were profiled using targeted metabolomics, the activation of the AhR/Nrf2 pathway was examined by Western blot, immunofluorescence, and qPCR, and gut microbiota composition was analyzed by 16S rRNA sequencing. Results: Postbiotic Nagqu4580 dose-dependently ameliorated DSS-induced UC in mice, as evidenced by reduced DAI scores, mitigated colon shortening and histological damage, decreased inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored intestinal barrier function by upregulating tight junction proteins (Claudin-1, ZO-1, Occludin). Mechanistically, postbiotic Nagqu4580 inhibited intestinal epithelial ferroptosis by reducing MDA and 4-HNE levels, restoring the GSH/GSSG balance, downregulating ACSL4, and upregulating GPX4. Serum metabolomics revealed that postbiotic Nagqu4580 reshaped tryptophan metabolism, increasing beneficial metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) and decreasing potentially harmful metabolites such as 3-indoxyl sulfate (3-IS). 16S rRNA sequencing further revealed that the postbiotic Nagqu4580 partially reversed DSS-induced gut microbiota dysbiosis, with a slight increase in the abundance of beneficial genera and a significant reduction in the abundance of pro-inflammatory genera. Furthermore, postbiotic Nagqu4580 significantly activated the AhR/Nrf2 signaling pathway, enhancing the expression of AhR, Nrf2, and their downstream antioxidant genes HO-1 and GPX4. Conclusions: Postbiotic Nagqu4580 alleviates UC by inhibiting intestinal epithelial ferroptosis. Our data suggest that this protective effect is associated with the remodeling of gut microbiota-related tryptophan metabolism and subsequent activation of the AhR/Nrf2 antioxidant axis. Our findings highlight the therapeutic potential of postbiotic Nagqu4580 as a postbiotic agent for UC. Full article

Background: Perilla seed oil (PSO) is a high-nutritional-value oil and widely used in functional foods, and derives from the mature seeds of Perilla frutescens. This study aimed to systematically evaluate the nutritional characteristics and safety of PSO, as well as to investigate its lipid-modulating effects and the underlying changes in gut microbiota in hyperlipidemic conditions. Methods: The nutritional characteristics of PSO (prepared via seed cleaning, cold-pressing, filtration, and solvent extraction) were evaluated by comparing it with 15 representative vegetable oils, focusing on fatty acid composition, total phenolic and flavonoid contents, metal elements, and physicochemical indices. The safety of PSO was assessed through acute oral toxicity testing in Kunming mice (doses: 2.5, 5, 10 g/kg) with general observations, histopathological examination, and serum biochemical analysis. Additionally, a high-fat diet (HFD)-induced hyperlipidemic Sprague-Dawley (SD) rat model was established to explore PSO’s lipid-modulating effects and its regulatory role in gut microbiota, using serum biochemical detection, liver pathology examination, 16S rRNA gene sequencing, and short-chain fatty acid (SCFA) analysis. Results: PSO possessed the highest α-linolenic acid (ALA) content among the tested oils, along with a favorable unsaturated fatty acid ratio. Notably, PSO was rich in zinc and free of toxic elements. In HFD-fed rats, 10 g/kg PSO significantly reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, increased high-density lipoprotein cholesterol (HDL-C), and alleviated hepatic damage. Moreover, PSO modulated gut microbiota by enriching probiotic populations and elevating intestinal production of short-chain fatty acids (SCFAs), particularly propionate and butyrate. Conclusions: PSO is a nutritionally rich and safe edible oil with notable lipid-modulating properties, highlighting its potential as a dietary intervention for preventing lipid metabolism disorders. Full article

Background: Glucose and lipid metabolism disorders are characterized by hyperglycemia, dyslipidemia, hepatic oxidative stress, lipid accumulation, and gut microbiota dysbiosis, all of which contribute to progressive metabolic dysfunction and tissue injury. As a plant extract mixture derived from mulberry leaves, lotus leaves, and Eucommia leaves, MELHAC (Mulberry–Eucommia–Lotus Herbal Aqueous Complex) was developed as a medicinal and edible formula with potential multi-component metabolic regulatory activity. In the present study, we systematically evaluated the effects of MELHAC on glucose and lipid metabolic abnormalities in high-fat diet (HFD) plus alloxan-induced mice. Methods: The phytochemical profile of MELHAC was characterized using untargeted LC–MS and network pharmacology. Its metabolic effects were evaluated in HFD plus alloxan-induced mice by measuring fasting blood glucose, serum lipid parameters, glucose tolerance, hepatic oxidative stress markers, histopathological changes, hepatic lipid accumulation, gut microbiota composition, and preliminary safety indices. Results: Chemical characterization revealed that MELHAC contains abundant bioactive constituents dominated by flavonoids, phenolic acids and alkaloids. In vivo experiments demonstrated that MELHAC lowered fasting blood glucose, total cholesterol and triglyceride levels, while ameliorating glucose intolerance and pathological damage in the liver, kidney and pancreas. MELHAC also improved liver-related biochemical abnormalities, increased hepatic superoxide dismutase, decreased malondialdehyde, and reduced hepatic lipid accumulation, indicating protective effects against oxidative stress and steatosis associated with metabolic dysfunction. In addition, MELHAC modulated gut microbial community structure and differential taxa linked to metabolic homeostasis. Short-term high-dose administration did not cause obvious abnormalities in serum biochemical, hematological, or histopathological indices. Conclusions: These findings suggest that MELHAC has potential as a plant-derived functional ingredient for improving glucose and lipid metabolic disorders and may provide an experimental basis for the future development of functional foods targeting metabolic health. Full article

Beyond their established role in lipid digestion, bile acids function as key metabolic and immune signaling molecules. This review synthesizes recent advances in bile acid metabolism within the context of gout and hyperuricemia, proposing a gut–liver–joint crosstalk framework. Dysregulated bile acid metabolism—characterized by a reduced total bile acid pool, decreased hydrophobic secondary bile acids, elevated 12α-hydroxy bile acids, and impaired enterohepatic circulation—has been mechanistically linked to both hepatic urate overproduction via the PPAR-α/xanthine oxidase pathway and monosodium urate crystal-induced NLRP3 inflammasome activation, although human causal evidence remains to be established. The nuclear receptor FXR suppresses NLRP3 at the transcriptional level, while the membrane receptor TGR5 acts post-translationally through Cyclic adenosine monophosphate/Protein Kinase A (cAMP/PKA) and Glucagon-like peptide-1 (GLP-1) signaling. Gut microbiota dysbiosis amplifies these abnormalities through a vicious cycle of reduced bile acid signaling, increased intestinal permeability, and systemic endotoxemia. Based on these insights, we summarize five therapeutic strategies: FXR modulators, TGR5 agonists, microbiota-based interventions, natural products, and ursodeoxycholic acid replacement therapy. Future research should prioritize gout-specific preclinical models, clinical trials of TGR5 agonists, standardized microbiota-based therapies, dual-target molecules, and personalized patient stratification based on bile acid profiles. Full article