Search Results (57)

Hyperlipidemia (HL) is a major metabolic disorder and a critical risk factor for cardiovascular diseases, closely associated with oxidative stress, inflammation, and disrupted cholesterol homeostasis. Freeze-dried Poecilobdella manillensis powder (FDPMP), a traditional medicinal product, has shown therapeutic potential against hyperlipidemia; however, its underlying mechanisms remain largely unclear. In this study, HL was induced in ApoE^−/− mice by feeding a high-fat diet (HFD) for eight weeks, during which FDPMP or simvastatin (positive control) was orally administered daily. Concurrently, an in vitro foam cell model was established by exposing RAW264.7 macrophages to oxidized low-density lipoprotein (ox-LDL, 80 μg/mL) for 24 h, with FDPMP pretreatment applied 30 min prior to ox-LDL stimulation. Following intervention, serum lipid profiles, hepatic oxidative stress markers, histopathological changes, and cholesterol metabolism-related gene and protein expression were systematically evaluated. FDPMP administration significantly improved serum lipid profiles by reducing triglycerides, total cholesterol, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol levels. Additionally, FDPMP alleviated histopathological damage in the liver, kidney, and heart, enhanced antioxidant enzyme activities, and attenuated oxidative stress. Untargeted metabolomic analysis revealed that FDPMP markedly modulated key metabolic pathways, including choline metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. Mechanistically, FDPMP restored cholesterol homeostasis through dual regulation of cholesterol metabolism, characterized by upregulation of cholesterol 7α-hydroxylase (CYP7A1) to promote bile acid-mediated cholesterol excretion, alongside downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and synthase (HMGCS1) to inhibit cholesterol biosynthesis. In vitro, FDPMP effectively suppressed ox-LDL-induced foam cell formation, reduced intracellular lipid accumulation, and mitigated oxidative stress in macrophages. Collectively, these findings demonstrate that FDPMP ameliorates hyperlipidemia through coordinated regulation of cholesterol synthesis and excretion, coupled with systemic metabolic reprogramming and antioxidative effects. This study provides mechanistic insights supporting FDPMP as a promising natural therapeutic candidate for hyperlipidemia and related metabolic disorders. Full article

The intricate interplay between the gut microbiome and the enteric nervous system remains a paramount focus in understanding the multifactorial pathogenesis of disorders of gut–brain interaction (DGBI), most notably irritable bowel syndrome (IBS). While the clinical entity of post-infectious IBS is well-established, the independent, long-term pathophysiological impact of iatrogenic antibiotic exposure is garnering critical attention within neurogastroenterology. This narrative review provides a comprehensive synthesis of current epidemiological and mechanistic evidence positioning antibiotic-induced microbial depletion as a potential predisposing factor for incident IBS. By evaluating recent literature, we highlight epidemiological trends demonstrating a consistent, dose-dependent relationship between cumulative antibiotic courses, particularly broad-spectrum agents, and an elevated risk of developing IBS, independent of prior acute enteric infections. Furthermore, we explore the mechanistic underpinnings of this association, focusing on how systemic antibiotics induce persistent, detrimental alterations in commensal diversity. This resulting dysbiosis initiates a proposed cascade of downstream consequences, including compromised epithelial barrier integrity, persistent low-grade mucosal inflammation, and altered bile acid metabolism. These localized disruptions serve as established triggers for visceral hypersensitivity and dysregulated gastrointestinal motility communicated via the gut–brain axis. Ultimately, this review underscores that antibiotic exposure may act as a significant, modifiable risk factor for IBS pathogenesis. Recognizing this substantial iatrogenic risk reinforces an urgent clinical imperative for stringent antimicrobial stewardship and emphasizes the necessity for future research directed toward prophylactic, microbiome-sparing strategies to mitigate the escalating global burden of DGBIs. Full article

Background/Objectives: Metabolically dysregulated-associated steatotic liver disease (MASLD) is a complex, multifactorial disorder characterised by hepatic lipid accumulation, insulin resistance, oxidative stress, and dysfunction of the gut–liver axis. Given its intricate pathophysiology, multi-target nutritional strategies represent a promising complementary approach. This study aimed to evaluate the biological effects of a multi-component nutraceutical formulation using an integrated in vitro platform replicating intestinal, hepatic, and pancreatic–liver interactions. Methods: The formulation was tested on Caco-2 intestinal cells to assess cell viability, transepithelial electrical resistance (TEER), probiotic functional properties, and glucose absorption. Intestinally processed metabolites were then applied to HepaRG liver cells under hyperglycemic (glucose) or lipotoxic conditions (oleic acid/palmitic acid) to analyse lipid accumulation, cholesterol biomarkers (HMGR, LDL), bile acid production, and cellular damage (ALT, AST). Finally, a pancreas–liver co-culture model (EndoC-βH5 and HepaRG) was employed to investigate insulin secretion and downstream hepatic metabolic signalling (IRS1, GLUT2, glycogen). Results: The formulation preserved intestinal barrier integrity and enhanced probiotic functionality, including aggregation and hydrophobicity. In hepatic models, the treatment significantly reduced intracellular lipid accumulation and triglycerides, while increasing bile acid production and improving cholesterol profiles. Under steatotic stress, it lowered transaminase levels and downregulated lipogenic signalling. In the pancreas–liver axis model, the formulation restored glucose-stimulated insulin secretion and improved hepatic metabolic signalling by increasing IRS1 levels and glycogen synthesis, indicating enhanced insulin sensitivity. Conclusions: These findings support the biological plausibility of a multi-target nutraceutical approach for MASLD. The formulation demonstrates coordinated beneficial effects on intestinal barrier function, hepatic lipid management, and glucose metabolism, providing a strong rationale for further clinical investigation. Full article

Background/Objectives: Atherogenic dyslipidemia is a major cardiometabolic risk factor characterized by elevated circulating triglycerides (TGs), reduced HDL-C, and increased levels of atherogenic lipoproteins. Curcumin, a polyphenolic compound considered the main bioactive component of turmeric (Curcuma longa), has attracted growing interest because of its potential lipid-modifying and anti-inflammatory properties. This scoping review aimed to evaluate evidence from randomized controlled trials (RCTs) on the efficacy of curcumin supplementation in the management of atherogenic dyslipidemia and to summarize current mechanistic evidence related to curcumin absorption, metabolism, and regulation of lipid homeostasis. Methods: A PRISMA-ScR-guided scoping review was performed across five databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase). RCTs evaluating curcumin supplementation in atherogenic dyslipidemia or related cardiometabolic conditions were systematically identified and synthesized. Mechanistic and preclinical evidence was identified through separate topic-specific searches of PubMed, Scopus, and Web of Science, supplemented by citation searching, and was synthesized narratively. Results: Twenty-two RCTs published between 2008 and 2025 were included. Most studies involved patients with cardiometabolic disorders, including type 2 diabetes mellitus with hyperlipidemia, metabolic syndrome, and polycystic ovary syndrome. Curcumin supplementation, administered in various formulations and dosages, showed overall favorable effects on plasma lipid profiles, particularly TGs and LDL-C, although the magnitude of these effects varied across studies. Mechanistic and preclinical evidence suggested that curcumin may modulate multiple pathways involved in lipid homeostasis, including intestinal cholesterol uptake, hepatic lipogenesis, cholesterol synthesis, fatty acid oxidation, bile acid metabolism, and reverse cholesterol transport. Conclusions: Current evidence suggests that curcumin may improve atherogenic lipid profiles through pleiotropic effects on lipid metabolism and cholesterol homeostasis. The clinical efficacy of curcumin appears to depend substantially on formulation-related bioavailability. Despite inter-study heterogeneity, curcumin shows potential as an adjunctive strategy for the management of atherogenic dyslipidemia and associated metabolic disorders. Full article

Cardiometabolic diseases are increasingly understood as disorders involving compartment-specific redox disruption rather than a uniform excess of reactive oxygen species. This narrative review synthesizes evidence for a proposed gut microbiota–mitochondria ferroptosis framework in which dysbiosis-derived lipopolysaccharide, trimethylamine N-oxide, short-chain fatty acids, bile acids, and tryptophan metabolites may modulate mitochondrial reactive species production, antioxidant defenses, iron handling, lipid peroxide detoxification, and inflammatory signaling. The reference set was assembled through searches of PubMed and Web of Science Core Collection, supplemented by targeted Google Scholar searches and citation chaining during manuscript preparation and revision through June 2026 and was organized around microbial metabolites, mitochondrial redox biology, ferroptosis pathways, disease-specific evidence, and redox-targeted interventions. Because this is a narrative synthesis rather than a systematic review, the framework should be interpreted as hypothesis-generating rather than as a systematically validated pathological model. Across atherosclerosis, diabetic cardiomyopathy, metabolic dysfunction-associated steatotic liver disease, obesity-associated insulin resistance, chronic kidney disease, and cardiorenal metabolic injury, the most consistent mechanistic links involve mtROS, impaired mitophagy, glutathione/GPX4 and SLC7A11 dysfunction, ACSL4-dependent lipid peroxidation, Nrf2 signaling, NLRP3 activation, and cGAS-STING-associated inflammation, although human causal evidence remains uneven. Importantly, much of the current literature supports local links within this sequence rather than a fully verified dysbiosis–metabolite–mitochondria ferroptosis–organ dysfunction chain in the same study. We therefore emphasize evidence tiers, terminology discipline, and biomarker requirements when interpreting ferroptosis-sensitive injury. Polyphenols, flavonoids, probiotics, postbiotics, melatonin, CoQ10-related strategies, mitochondria-targeted antioxidants, and ferroptosis-sensitive approaches may be most translatable when paired with microbiome, metabolomic, lipidomic, pharmacokinetic, and redox biomarkers. Full article

Background/Objectives: Bile acid synthesis disorders (BASDs) represent a distinct category of progressive familiar cholestatic liver disease. A novel targeted mass spectrometry assay was developed for the accurate measurement of the major urinary atypical bile acids and bile alcohols that are biomarkers for HSD3B7, AKR1D1, CYP7B1 and CYP27A1 deficiencies, the four most common BASDs. Methods: Stable-isotope dilution UPLC tandem mass spectrometry was used for the simultaneous quantification of 12 key atypical bile acid biomarkers in urine from patients with BASD. Typical concentration ranges for these metabolites were established from urine samples from patients with biochemically and/or genetically confirmed BASD and compared with non-cholestatic and cholestatic controls. Results: The separation of major 3β-hydroxy-Δ⁵-bile acid sulfates, taurine- and glycine-conjugated 3-oxo-Δ⁴-bile acids, and bile alcohol glucuronides was achieved in a 20 min chromatographic run with intra- and inter-batch imprecisions of <15% for all metabolites. The mean ± SEM urinary concentration of total 3β-sulfated-Δ⁵-cholenoic acids in patients with HSD3B7 deficiency was 704 ± 204 µmol/L (n = 22), approximately 2000-fold higher than in cholestastic patients (n = 168) or non-cholestatic controls (n = 127). Similarly, the concentration of 5β-cholestane-3α,7α,12α,24,25-pentol-glucuronide, the major bile alcohol, in patients with CYP27A1 deficiency was 95 ± 17 µmol/L (n = 12). For CYP7B1 deficiency, two confirmed cases showed elevated levels (average, 7.5 µmol/L) of the glycine conjugate of 3β-sulfooxy-Δ⁵-bile acid. In AKR1D1 deficiency, total 3-oxo-Δ⁴-bile acids in urine were elevated (81 ± 16 µmol/L, n = 48), but concentrations showed overlap with cholestatic and non-cholestatic controls. Conclusions: A novel quantitative tandem mass spectrometry assay is described for the measurement of the major atypical metabolites and biomarkers in urine applicable to the accurate monitoring of treatment responses, and for the first time typical concentration ranges are established for each of these BASDs. Full article

Peroxisomes are essential metabolic organelles that support core aspects of cellular homeostasis. In the hepatocytes, peroxisomes govern key aspects of cellular homeostasis, including processing lipid substrates that are inadequately handled by mitochondria, controlling hydrogen peroxide metabolism, and regulating bile acid synthesis. Increasing evidence indicates that these organelles are not merely auxiliary metabolic compartments but active contributors to the development and progression of liver disease. Dynamic alterations in peroxisomal proteins and function are being noted. Across metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic disorders, fibrosis, and hepatocellular carcinoma, peroxisomes undergo remodeling that shows a change from adaptive reactions to maladaptive states. These changes perturb signaling pathways that regulate inflammation, stress responses, and cell fate. In addition, because peroxisomes operate within an interconnected organelle network, their dysfunction propagates to mitochondria, endoplasmic reticulum, and other cellular systems, amplifying metabolic and cellular stress. This review summarizes current understanding of how peroxisomal pathways contribute to liver disease, highlighting mechanisms involving lipid accumulation, oxidative stress, and disrupted organelle crosstalk. How peroxisome-dependent control of circulating metabolites links hepatic injury to extrahepatic organ systems is further discussed. At the end, emerging therapeutic strategies for liver disease targeting peroxisomal pathways are discussed. Together, the emerging understanding of peroxisomal remodeling, metabolic regulation, organelle crosstalk, and inter-organ communication positions peroxisomes as active and dynamic regulators of liver disease and potential targets for therapeutic intervention. Full article

The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe–host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood–retinal barrier stability, supporting the emerging concept of the gut–eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren’s syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions. Full article

Objective: Based on previous findings on the Lingguizhugan (LGZG)-mediated gut–liver axis, this study clarifies the therapeutic mechanisms of LGZG in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on the gut microbiota–bile acid–TGR5 (GPBAR1) axis. Methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce MASLD, followed by 4-week LGZG intervention (21.57 g/kg/day, oral gavage). Metabolic phenotypes, gut microbiota (16S rRNA sequencing), serum/hepatic bile acids (targeted metabolomics), and molecular targets (qPCR/Western blot) were analyzed. Results: LGZG significantly alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis, while enhancing whole-body energy expenditure (increased oxygen consumption (VO₂), and heat production (p < 0.05). It also reduced serum ALT (p < 0.001) and AST levels (p < 0.01). Mechanistically, LGZG remodeled the gut microbiota, specifically increasing Akkermansia, Bifidobacterium and Lachnospiraceae_NK4A236_group while decreasing Lactobacillus. This shift inhibited the intestinal FXR-Fgf15 axis, concurrently activating the hepatic alternative bile acid synthesis pathway (upregulating CYP27A1 and CYP7B1 protein expression; p < 0.001 and p < 0.01, respectively). Consequently, systemic accumulation of non-12α-hydroxylated bile acids (non-12-OH BAs) such as hyocholic acid (HCA) and 7-ketolithocholic acid (7-ketoLCA) occurred—known TGR5 agonists and intestinal FXR antagonists. These changes elevated serum GLP-1 levels (p < 0.05) and activated adipose TGR5-cAMP/PKA/CREB signaling. The metabolic benefits primarily originated from non-12-OH BAs enrichment and TGR5-mediated adipose browning, not hepatic FXR activation. Conclusions: Our findings show that LGZG ameliorates MASLD by remodeling bile acid profiles via intestinal FXR-Fgf15 axis inhibition and hepatic alternative synthesis pathway activation. This study highlights the TGR5-targeting properties of LGZG, providing a mechanistic basis for its therapeutic use in metabolic disorders. Full article

Background/Objectives: Intestinal dysbiosis is a pivotal trigger of type 2 diabetes mellitus (T2DM). Our previous studies confirmed that composite probiotics derived from fermented camel milk (CPCM), containing Lactobacillus harbinensis and 13 other strains, can ameliorate glucose and lipid metabolism in T2DM mice by reshaping bile acid profiles, and its effect may be associated with the PPARγ-LXRα-NPC1L1 signaling pathway. Methods: Metagenomic analysis characterized alterations in intestinal microbiota structure and functional genes post-CPCM intervention, proteomic analysis detected changes in protein expression profiles related to glucose and lipid metabolism in mice, and Caco-2 cells were used for in vitro validation to clarify the regulatory effect of exopolysaccharides (EPS) (the active component of CPCM) on the PPARγ-LXRα-NPC1L1 signaling pathway. Results: The results showed that CPCM significantly improved glucose and lipid metabolism and remodeled the intestinal flora structure in mice, markedly enriching beneficial bacteria such as Lactobacillus and Akkermansia and enhancing the expression of functional genes related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway and short-chain fatty acid synthesis in the microbiota. Proteomic analysis revealed that CPCM reversed the expression of key proteins involved in fatty acid oxidation and transport, thereby restoring the function of the PPAR signaling pathway. In vitro experiments validated that extracellular polysaccharides, the active component of CPCM, significantly upregulated the expression of PPARγ and liver X receptor α (LXRα) and inhibited the expression of Niemann–Pick C1-Like 1 (NPC1L1), a cholesterol absorption transporter, in Caco-2 cells. Conclusions: In conclusion, CPCM ameliorates glucose and lipid metabolic disorders in T2DM through multiple mechanisms: reshaping the intestinal probiotic community, enhancing its beneficial metabolic functions, restoring the activity of the PPARγ-LXRα signaling pathway, and subsequently downregulating NPC1L1. Full article

Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax china L. extract (SCE) on MAFLD and to elucidate the pharmacological mechanisms. Methods: A rat model of MAFLD was induced through a high-fat diet (HFD), and the model rats subsequently received SCE as a therapeutic intervention for six weeks. The analysis involved 16S rDNA sequencing, untargeted fecal metabolomics, and targeted bile acid metabolomics to investigate the effects of SCE on the gut microbiota and bile acid metabolism. Results: Hepatic steatosis and lipid accumulation were significantly alleviated by the SCE treatment. SCE treatment modulated the gut microbiota disorder, by enhancing the relative abundance of the beneficial gut microbiota, including Clostridium, Oscillospira, and Romboutsia. Untargeted fecal metabolomics revealed a significant enrichment of the metabolites in secondary bile acid biosynthesis. Targeted bile acid metabolomics revealed that SCE reversed the abnormal fecal bile acid metabolic profile, such as HDCA, LCA, and T-β-MCA. These changes activated FXR and PPARα receptors to improve the lipid metabolism by regulating bile acid synthesis. Conclusions: Our study provides evidence that SCE alleviates MAFLD through regulation of the gut microbiota, bile acid metabolism, and activation of the FXR/PPARα pathway, illustrating the mechanism of action of SCE in MAFLD from a novel perspective, and further highlights its therapeutic potential. Full article

Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns—often referred to as enterotype-like clusters—correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance for metabolic and gastrointestinal health. This narrative review synthesizes current evidence describing the interplay between microbial composition, BA metabolism, and metabolic dysfunction. A structured literature search was conducted in PubMed, Web of Science, EMBASE, and Scopus using predefined keywords related to bile acids, microbiome composition, metabolic disorders, and enterotypes. Studies were screened for human clinical relevance and mechanistic insights into BA–microbiome interactions. Across the evidence base, Bacteroides-, Prevotella-, and Ruminococcus-associated community types consistently demonstrate different BA transformation capacities that influence secondary BA production and downstream host signaling through FXR and TGR5. These differences are linked to variation in metabolic dysfunction-associated steatotic liver disease, obesity, type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Host genetic variations in BA synthesis, transport, and signaling further modify these microbiome–BA interactions, contributing to the heterogeneity of dietary intervention responses. Overall, the literature supports a model in which microbiome-derived BA profiles act as metabolic phenotypes that shape host lipid and glucose homeostasis, inflammation, and gut–liver axis integrity. Emerging clinical applications include microbiome-stratified dietary strategies, targeted probiotics with defined BA-modifying functions, and therapeutic approaches that align BA-modulating interventions with an individual’s microbial metabolic capacity. Establishing integrated biomarker platforms combining microbiome clustering with BA profiling will be essential for advancing precision nutrition and personalized management of metabolic and gastrointestinal diseases. Full article

Hypertension is a cardiovascular disorder characterized by sustained elevation of arterial blood pressure, in which vascular dysfunction serves as a key initiating factor leading to target organ injury. The indole alkaloid edulinine (Edu) represents a potential therapeutic agent for hypertension, although its specific mechanisms remain unclear. This study investigated the protective effects of Edu on vascular endothelial injury in N-⁠nitro-⁠L-⁠arginine-induced hypertensive rats using physiological, biochemical, and histopathological assessments. Through integrated proteomic and metabolomic analyses, we examined Edu’s effects on thoracic aortic tissue proteins and serum metabolic profiles to elucidate its molecular mechanisms. The results demonstrated that Edu exhibited superior antihypertensive efficacy compared to sodium nitroprusside and effectively ameliorated hypertension-induced left ventricular systolic dysfunction. Furthermore, proteomic analysis indicated that compared with the Model group, Edu showed significant intersections in the tricarboxylic acid cycle, fatty acid degradation, oxidative phosphorylation, and fatty acid elongation pathways. These pathways are of great significance to lipid metabolism and energy metabolism and are closely related to fatty acid elongation and myocardial contraction. In the fatty acid degradation pathway, the proteins up-regulated by Edu almost exactly correspond to those down-regulated by the Control group. Metabolomics analysis revealed that Edu exerts its antihypertensive effects primarily by regulating biological pathways involved in bile acid metabolism, fatty acid metabolism, and lipid metabolism. The integrated analysis of metabolomics and proteomics demonstrated that Edu markedly reduced the abnormal up-regulation of OXSM and MECR in hypertensive rats, suggesting that Edu may systematically regulate the balance of the fatty acid metabolic network by regulating the carbon chain initiation and elongation processes in fatty acid synthesis, as well as the key reductive reactions in mitochondrial β-oxidation. In summary, the potential mechanism of the protective effect and antihypertensive effect of Edu on the thoracic aorta of L-NNA-induced hypertensive rats may be inhibiting the up-regulation of OXSM and MECR expression, regulating the dynamic balance of fatty acid degradation and synthesis, and improving fatty acid metabolism disorders. These findings indicate that Edu holds substantial research value as a potential therapeutic candidate for hypertension. Full article

Commercial feeds formulated for Larimichthys crocea are commonly used in intensive farming of Larimichthys polyactis; however, their nutritional composition is suboptimal for the latter. The study evaluated the effects of dietary chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) supplementation on mitigating nutritional mismatch-induced growth retardation and hepatopancreatic–intestinal metabolic disorders in L. polyactis. Fish were fed seven feeds: a commercial feed (control) and feeds supplemented with 300, 600, and 1200 mg/kg of CDCA or UDCA. Results showed that both bile acids (BAs) supplementation improved growth, altered thyroid hormone metabolism, with significant changes in hepatopancreatic–intestinal types of deiodination. Both BAs increased hepatopancreatic energy metabolism and cholic acid synthesis, while inducing hepatopancreatic oxidative damage. Notably, 300 mg/kg CDCA and 600 mg/kg UDCA significantly reduced hepatopancreatic vacuolation and lipid accumulation, which was associated with enhanced protease and lipase activities (p < 0.05). Dietary both BAs supplementation enhanced intestinal antioxidant capacity, but contributed to the inflammation, with 300 mg/kg UDCA improving intestinal mucosal morphology (p < 0.05). These findings suggest that supplementation with dietary 300 mg/kg CDCA, 300 and 600 mg/kg UDCA could alleviate growth restriction and liver–intestinal structural damage caused by nutritional mismatch, reduce hepatic fat accumulation, and enhance intestinal antioxidant capacity of L. polyactis. Full article

Background/Objectives: HIV infection has been associated with an increased incidence of non-communicable comorbidities, including metabolic disorders. This phenomenon has been linked to gut microbiota dysbiosis, which involves not only changes in bacterial composition but also functional alterations in metabolite production. The objective of this study was to describe the impact of intestinal microbial metabolomics on the development of type 2 diabetes in people living with HIV. Methods: This study provides a narrative synthesis of current evidence addressing the role of gut microbiota-derived metabolites in immunometabolic regulation and their implications in HIV-associated type 2 diabetes. Results: Microbial metabolites play a fundamental role in regulating key physiological processes such as intestinal permeability, systemic immune activation, and glucose metabolism. Compounds such as short-chain fatty acids, tryptophan catabolites, secondary bile acids, trimethylamine N-oxide, and imidazole propionate have been shown to significantly influence immunometabolic balance. In people living with HIV, these microbial products may exert diverse effects depending on their chemical nature and the molecular pathways they activate in peripheral tissues. The interaction between dysbiosis, chronic low-grade inflammation, and HIV-associated metabolic disturbances may contribute to the early onset of type 2 diabetes beyond traditional risk factors. Conclusions: Recognizing the role of microbial metabolites in the context of HIV infection is essential to broaden our pathophysiological understanding of associated metabolic comorbidities. It also opens opportunities to develop more comprehensive diagnostic and therapeutic strategies that include modulation of the gut microbiota and its metabolic activity for the prevention and management of type 2 diabetes in this population. Full article