Search Results (1,586)

The axis linking the gut to the brain to the immune system connects all tissues involved—bacteria, immune cells, metabolism and the CNS—through a multidirectional communication network. Several studies have confirmed that when this axis is disrupted, it can be responsible for Alzheimer’s disease, Parkinson’s disease, obesity, type 2 diabetes, and NAFLD, and the main consequences come from increased systemic inflammation, altered regulation of immune cells, the production of microbial metabolites that alter signals to the immune cells and nervous system, increase in oxidative stress, breakdown of the gut barrier, and more. In recent years, advanced multi-omics technologies, such as metagenomics, transcriptomics, metabolomics, proteomics, and single-cell sequencing, have provided significant advancement in our understanding of all of the interacting nodes involved in the gut–brain–immune axis. These advanced sequencing technologies can characterize the microbial communities, host immune cells, metabolic profiles, and the degree of cell heterogeneity during a specific disease. Combining multi-omics information can reveal a few shared pathways between neurodegenerative and metabolic disorders, such as NF-κB, NLRP3 inflammasome activation, mitochondrial dysfunction, changes in SCFA metabolism, and the alteration of microbial populations in Alzheimer’s and Parkinson’s disease; metabolic dysbiosis and increased risk for Parkinson’s disease; or changes in gut-to-brain-to-immune signaling contributing to diabetes complications and NAFLD. Artificial intelligence (AI) and machine learning are becoming promising tools for detecting biomarkers from these datasets, extracting knowledge, interpreting systems biology, and helping with developing precision medicine. In this review, we summarize current evidence that supports the role of the gut–brain–immune axis in neurodegenerative and metabolic diseases, highlighting results gained with the utilization of multi-omics approaches. We will describe the key microbial, immune, and metabolic pathways involved in pathogenesis and therapeutic approaches including psychobiotics, tailored nutrition, modulation of the microbiome, and metabolite interventions, discussing future perspectives of the translation of the gut–brain–immune axis knowledge into clinical practice. Full article

Obesity and type 2 diabetes mellitus (T2DM) represent intertwined global epidemics driven by gut dysbiosis, chronic inflammation, and impaired SCFA production, identifying the microbiome as a therapeutic target. This review synthesizes mechanistic insights and clinical evidence on the role of probiotics as microbiome modulators in the management of metabolic disease. A comprehensive literature search across PubMed, Scopus, Web of Science, and Google Scholar up to May 2026 identified ~230 records using keywords such as probiotics, SCFAs, obesity, and T2DM; a narrative synthesis integrated preclinical, RCT, and meta-analytic data without formal pooling due to heterogeneity. Probiotics restore eubiosis via strain-specific mechanisms, Lacticaseibacillus rhamnosus GG enhances tight junctions (ZO-1), Bifidobacterium breve BBr60 boosts butyrate cross-feeding, and pasteurized Akkermansia muciniphila remodels bile acids (FXR/FGF19), activating G-Protein Coupled Receptor 41 (GPR41)/43-GLP-1 signaling, Treg expansion, and NF-κB suppression. Beyond immunometabolic effects, probiotics mitigate obesity- and T2DM-related oxidative stress by upregulating endogenous antioxidant enzymes (e.g., SOD, catalase, GPx), modulating Nrf2/Keap1 signaling, and reducing lipid peroxidation and other oxidative stress markers in experimental and clinical settings. Meta-analyses of RCTs reveal modest benefits: BMI reductions (~0.3 kg m⁻²), waist circumference (WC) reductions (1–2 cm), HbA1c reductions (0.3–0.4%), and improvements in homeostatic model assessment of insulin resistance (HOMA-IR), especially with multi-strain (>10⁹ CFU day⁻¹, ≥12 weeks) synbiotics. Innovative strategies—synbiotics, postbiotics, AI-tailored consortia, and fermented dairy—address engraftment and response variability. Current guidelines recommend 10⁹–10¹¹ CFU day⁻¹ using multi-strain formulations for 12–24 weeks alongside lifestyle measures, with regimen selection tailored to the dysbiosis phenotype (e.g., NAFLD). Future longitudinal RCTs integrating multi-omics endpoints with AI-driven strain selection should refine—and ultimately individualize—precision probiotic strategies for metabolic therapy. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver condition globally, affecting one-quarter of the adult population. Non-invasive metabolic indices offer a pragmatic alternative to liver biopsy for population-level steatosis screening. We aimed to systematically compare the diagnostic performance of four widely used metabolic indices—TyG, LAP, FLI, and VAI—and to derive a novel composite score that demonstrably surpasses each constituent index. Methods: Retrospective cross-sectional study; 1204 consecutive adults undergoing abdominal ultrasonography at a single tertiary centre (study period: 2024–2025; data collection period: January–April 2026); steatosis graded 0–3 by certified radiologists; four metabolic indices retrieved from pre-calculated columns; novel composite score derived by binary logistic regression with 10-fold stratified cross-validation (stratified by binary outcome); AUROC with 1000-iteration bootstrap 95% CI; and pairwise comparisons by the DeLong method. Results: Of 1204 patients (mean age 42.3 ± 12.5 years; 73.3% male; 13.4% with diabetes), steatosis grades were: Grade 0, 185 (15.4%); Grade 1, 539 (44.8%); Grade 2, 311 (25.8%); and Grade 3, 169 (14.0%). For significant steatosis (Grade ≥ 2), TyG achieved AUROC 0.884 [0.863–0.904] and LAP 0.883 [0.862–0.901], while FLI showed only moderate performance. The novel composite score achieved AUROC 0.896 [0.870–0.920] for any steatosis and 0.922 [0.906–0.938] for significant steatosis, significantly outperforming all four individual indices (DeLong p = 0.004 vs. TyG; p = 0.002 vs. LAP; p < 0.001 vs. FLI; p < 0.001 vs. VAI). Youden-optimal performance: sensitivity 87.1%, specificity 86.0%, and Youden index 0.731. Conclusions: A 10-fold cross-validated logistic composite of four metabolic indices significantly outperforms each constituent index for ultrasonographic hepatic steatosis detection. The composite score may serve as a practical, non-invasive tool for steatosis risk stratification pending external validation. Full article

Circadian Syndrome (CircS) links metabolic, behavioral, and mental health challenges to disrupted circadian rhythm. Hyperuricemia (HUA) is associated with cardiometabolic disorders; however, its connection to CircS remains incompletely understood. This study aims to determine if HUA can serve as a biomarker for CircS. We analyzed the National Health and Nutrition Examination Survey (NHANES) data (2005–2020) from 27,410 adults. CircS was defined as the presence of at least five out of eight components, encompassing the traditional metabolic syndrome criteria plus three additional factors: short sleep duration, depression, and non-alcoholic fatty liver disease (NAFLD). HUA was set at serum uric acid levels >6 mg/dL (357 µmol/L) for females and >7 mg/dL (416 µmol/L) for males. Multivariable logistic regression identified predictors of CircS, and dose–response relationships were explored. Of 27,410 participants, 2076 (7.57%) had CircS. HUA was found to be the strongest independent predictor of CircS, with an odds ratio (OR) of 3.26 (95% uncertainty interval (UI) 2.80–3.80, p < 0.001). Other important risk factors included chronic kidney disease (CKD) (OR 2.80), female sex (OR 1.44), and smoking (OR 1.29). In addition, older age, lower educational level, and lower income were also linked with higher risk. Higher uric acid levels were consistently linked to metabolic components of CircS more strongly than to depression and short sleep. In conclusion, HUA is linked with a greater risk of CircS. Although testing is simple and widely available, it could be used for early risk detection. Future studies should determine if lowering uric acid improves circadian health. Full article

Selenium (Se) is an essential trace element that exerts pleiotropic effects on host physiology, yet the mechanisms by which it coordinates systemic health remain incompletely understood. Emerging evidence regards the gut microbiota as a key mediator of Se biological functions, giving rise to the Se–gut–tissue axis. This review synthesizes the current research progresses on how dietary Se may shape gut microbial composition and metabolism, and how these microbial shifts are associated with protective effects in both intestinal and extra-intestinal tissues. Se sources (particularly organic or new synthetic form) may bidirectionally interact with gut bacteria by enriching beneficial genera such as Akkermansia, Lactobacillus, and butyrate-producing Clostridia, while suppressing opportunistic pathogens. This microbial remodeling strengthens intestinal barrier integrity, enhances antioxidant and anti-inflammatory responses (e.g., via GPX, TrxR, and NF-κB suppression), and generates bioactive metabolites, notably short-chain fatty acids and secondary bile acids. Through these mechanisms, the Se–gut–microbiota axis may regulate distal organ homeostasis, including the liver (ameliorating NAFLD and acute injury), brain (counteracting neurodegeneration and modulating serotonin/GABA), muscle (improving mass and Se deposition), kidney (attenuating uremic toxin-induced ferroptosis), and reproductive organs. Despite encouraging progress, challenges remain in establishing causality, optimizing dose–response relationships, and translating findings into precision interventions. Full article

Background/Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disease worldwide, affecting approximately 25% of the global population. MAFLD represents a broad disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The availability of experimental models that faithfully reproduce human metabolic and hepatic pathology is essential for elucidating disease mechanisms and advancing therapeutic development. This review aims to critically evaluate commonly used rodent models of MAFLD and provide guidance for model selection based on specific research objectives. Methods: A narrative, semi-systematic literature search was performed using PubMed Central, Ovid MEDLINE, and Google Scholar. Rodent models were classified according to their mode of disease induction, including diet-induced, genetically engineered, chemically or pharmacologically induced, and combination models. Models were assessed based on frequency of use, relevance to different stages of MAFLD progression, metabolic fidelity, and suitability for mechanistic studies and preclinical therapeutic evaluation. Results: Diet-induced models incorporating high fat, fructose, and cholesterol most closely recapitulate human metabolic dysfunction and are highly relevant for translational research and drug screening. Nutrient-deficient diets induce rapid steatohepatitis and fibrosis but lack key features of metabolic syndrome. Genetic models enable the targeted interrogation of specific metabolic and inflammatory pathways, whereas chemical and combination models accelerate fibrosis and HCC development. No single rodent model fully reproduces the entire spectrum of human MAFLD. Conclusions: Rodent models remain indispensable tools for MAFLD research; however, their applicability depends on alignment with the defined experimental goals. Careful selection of models based on disease stage, dominant pathogenic mechanisms, and translational intent is essential for improving reproducibility and clinical relevance. This review provides a practical framework to guide investigators in choosing appropriate preclinical models for mechanistic studies and therapeutic development in MAFLD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of global chronic liver disease, with a prevalence of approximately 30%. This review outlines the diagnostic transition from the exclusionary non-alcoholic fatty liver disease (NAFLD) framework to the affirmative MASLD nomenclature, which mandates the presence of at least one of five specific cardiometabolic risk factors (CMRFs) to prioritize active pathophysiology. Beyond hepatic complications, MASLD drives systemic metabolic failure, significantly elevating risks for type 2 diabetes, hepatocellular carcinoma, and cardiovascular disease, the primary cause of mortality in this cohort. Clinical management relies on a standardized, two-tier risk-stratification pathway for advanced fibrosis. Primary care triage utilizes the Fibrosis–4 (FIB–4) index; a score < 1.3 excludes advanced disease via a high negative predictive value, whereas indeterminate or high scores require secondary validation via vibration-controlled transient elastography (VCTE) or the enhanced liver fibrosis (ELF) test to guide specialist referral. Although lifestyle modifications, principally a 7–10% weight reduction and Mediterranean diet adherence, remain foundational, management has transitioned toward disease-modifying pharmacotherapies. A pivotal breakthrough occurred with the 2024 FDA approval of resmetirom, a selective thyroid hormone receptor-beta (THR-β) agonist, for non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced fibrosis. Concurrently, the emergence of GLP-1 receptor agonists and multi-incretin mimetics offers a personalized, multi-target approach simultaneously addressing hepatic inflammation, glycemic control, and adiposity. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in patients with type 2 diabetes (T2D) and is associated with increased cardiovascular risk. However, the relative contribution of traditional cardiometabolic risk factors (CMRFs), hepatic fibrosis markers, and antidiabetic therapies to atherosclerosis remains unclear. Methods: We conducted a cross-sectional study including 46 patients with T2D and MASLD. Atherosclerotic cardiovascular disease (ASCVD) was defined as the presence of carotid atheromatosis, stroke, peripheral arterial disease, or ischemic heart disease, as assessed by imaging-based parameters. Clinical, metabolic, and treatment-related variables were analyzed, including age, Hemoglobin A1c (HbA1c), lipid profile, hepatic fibrosis indices such as Fibrosis-4 index (FIB-4), and antidiabetic therapies (sodium–glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and insulin). Multivariable regression models and receiver operating characteristic (ROC) curve analyses were used to evaluate associations and discriminative performance. Results: Traditional CMRFs were more strongly associated with ASCVD than hepatic fibrosis markers or antidiabetic therapies. Age was associated with ASCVD in several exploratory models, although this association was attenuated in the fully adjusted model. HbA1c showed the highest discriminative performance (AUC 0.77), indicating that chronic glycemic exposure is a major determinant of vascular disease in this cohort. In contrast, FIB-4 was not associated with ASCVD and did not improve model performance. Antidiabetic therapies, including SGLT2i and GLP-1 RAs, were not independently associated with ASCVD. Insulin therapy was more frequent among patients with ASCVD, but was not independently associated after adjustment. Conclusions: In patients with T2D and MASLD, ASCVD appears to be associated with traditional CMRFs, particularly chronic glycemic exposure, rather than hepatic fibrosis markers or treatment status. These findings highlight the central role of metabolic control in cardiovascular risk and suggest that the contribution of liver-related markers and therapeutic interventions may be more relevant in longitudinal settings. Full article

Cyanidin-3-O-Glucoside (C3G) is the primary anthocyanin-active component in bilberry, exhibiting various pharmacological activities such as antioxidant, anti-inflammatory, and lipid metabolism-regulating effects. To address the clinical need for non-alcoholic fatty liver disease (NAFLD) prevention and treatment, this study aimed to investigate the ameliorative effects of C3G on NAFLD pathology and elucidate its molecular mechanisms of protection via the AMPK pathway. After a one-week acclimatization period, 20 six-week-old SPF mice were randomly divided into four groups: normal diet control (NCD), high-fat diet model (HFD), HFD + L-C3G (100 mg/kg/day), and HFD + H-C3G (200 mg/kg/day). Except for the NCD group, the remaining groups were fed a 60% high-fat diet for four weeks to establish an early-stage NAFLD model, with successful model construction verified by weight and liver weight gain. From the fifth week onward, C3G groups received daily administration for four consecutive weeks, while control groups were given an equal volume of distilled water. Liver function, lipid metabolism, oxidative stress, and inflammatory levels were assessed using ELISA, H&E staining, and other methods. The results showed that C3G restored liver function in NAFLD mice, improved lipid metabolism disorders, reduced oxidative stress and inflammatory responses, and alleviated liver pathological damage. Mechanistic studies revealed that C3G regulated the expression of mRNA and proteins related to the AMPK/SIRT1/NF-κB signaling pathway, activating the pathway by upregulating AMPK and its upstream regulators while inhibiting NF-κB-mediated inflammatory responses. This study confirmed that C3G can ameliorate high-fat diet-induced NAFLD lesions by activating the AMPK/SIRT1/NF-κB pathway, providing a potential intervention strategy for NAFLD prevention and treatment. Full article

Dysfunction-associated steatotic liver disease (MASLD) is a newly introduced term for the condition previously known as nonalcoholic fatty liver disease (NAFLD). MASLD affects 38% of the global population and is now diagnosed based on the presence of steatosis but also with cardiometabolic risk factors indicating metabolic dysfunction. Chronic hepatitis B (CHB), another significant public health issue, impacts over 296 million people worldwide, or approximately 3.2% of the global population. Studies have consistently reported a complex relationship between MASLD and CHB. Previous studies indicate that MASLD may protect against high viral loads, while other studies indicate that coexisting MASLD and CHB may lead to more advanced fibrosis and an elevated risk of HCC. Additionally, numerous studies highlight a strong association between CHB and metabolic syndrome components. This review article examines the relationship between CHB and MASLD, considering what has been previously published. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced older exclusion-based terminology as the preferred term for steatotic liver disease associated with cardiometabolic risk factors. MASLD is now among the most common causes of chronic liver disease and may progress from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This updated rigorous narrative review synthesizes current evidence on MASLD diagnosis and management, with emphasis on the gut–liver axis and the therapeutic potential of combining probiotics with metformin. A structured narrative search was conducted in PubMed, PMC, ScienceDirect, Taylor & Francis, Cochrane Library, and Google Scholar using the keywords “MASLD”, “MAFLD”, “NAFLD”, “MASH”, “probiotics”, “synbiotics”, “metformin”, and “gut-liver axis”. The review was designed as a narrative synthesis rather than a systematic review. Current guidance supports stepwise risk stratification using serum fibrosis scores followed by elastography or advanced imaging when indicated. Ultrasonography remains accessible but has limited sensitivity for mild steatosis, is operator-dependent, and is not sufficient for comprehensive assessment of fibrosis or disease activity. Metformin is appropriate for type 2 diabetes mellitus and improves insulin resistance, but current guidelines do not recommend it as a targeted treatment for MASH because histological benefit has not been consistently demonstrated. Probiotics and synbiotics may improve aminotransferases, inflammatory markers, lipid parameters, intestinal barrier function, and gut dysbiosis; however, findings vary by strain, formulation, dose, treatment duration, population, and endpoint. The combination of probiotics and metformin is mechanistically plausible because it targets both metabolic dysfunction and intestinal dysbiosis, but human evidence remains limited. Larger, strain-specific, adequately powered trials using standardized MASLD criteria and clinically meaningful endpoints are required before routine clinical recommendations. Full article

Background/Objectives: Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) is an increasingly recognized phenotype occurring in individuals with normal body mass index (BMI), despite clinically important hepatic and cardiometabolic risk. This narrative review summarizes current evidence on its epidemiology, pathophysiology, diagnostic challenges, clinical outcomes, and management. Methods: A narrative literature review was conducted using PubMed, Embase, and Cochrane Library from database inception to March 2026. Relevant studies on lean MASLD/lean NAFLD, including cohort studies, meta-analyses, clinical trials, consensus statements, and practice guidelines, were prioritized. Results: Lean MASLD reflects interactions between visceral adiposity, insulin resistance, genetic susceptibility, sarcopenia, dietary and lifestyle factors, vitamin D deficiency, and gut microbiome alterations. Diagnosis is challenging because BMI and aminotransferase levels may underestimate metabolic vulnerability, MASH, or clinically significant fibrosis. Available data suggest increased liver-related events, liver-related mortality, and all-cause mortality compared with individuals without steatotic liver disease, although comparisons with non-lean MASLD remain heterogeneous. Resmetirom and semaglutide have expanded treatment options for noncirrhotic MASH with moderate to advanced fibrosis, but lean patients are underrepresented in pivotal trials. Conclusions: Lean MASLD is an underrecognized but clinically important phenotype. Earlier recognition, fibrosis risk stratification, sarcopenia assessment, cardiometabolic optimization, and lean-specific therapeutic research are needed to improve outcomes. Full article

Heat stress (HS) has emerged as a major environmental stressor, inducing oxidative stress and hepatic steatosis and impairing production performance and health in laying hens, with limited evidence-based nutritional interventions available. This study investigated the hepatoprotective effects of dietary silibinin (SIL) against chronic HS. In a 10-week trial, 252 43-week-old Hy-Line Brown hens were exposed to daily HS (32 ± 1 °C, temperature–humidity index [THI] > 73) and fed either a basal diet or one supplemented with 100 mg/kg SIL. SIL significantly increased laying rate (p < 0.05) and improved albumen height, Haugh units, and shell strength by week 8 (p < 0.05). Histological analysis showed a 48% reduction in non-alcoholic fatty liver disease (NAFLD) activity score, with significantly decreased hepatic triglyceride content (p < 0.05); Oil Red O staining confirmed reduced lipid droplet accumulation. SIL restored redox balance by increasing plasma, hepatic total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05), increasing hepatic catalase (CAT) and glutathione (GSH) levels while decreasing malondialdehyde (MDA) (p < 0.05). Untargeted plasma metabolomics identified 11 key metabolites related to 2-oxoglutarate and purine metabolism, while hepatic transcriptomics revealed 835 differentially expressed genes primarily in the PPAR signaling and fatty acid biosynthesis pathways. SIL suppressed de novo lipogenesis via downregulation of ACACA and FASN, and enhanced β-oxidation through upregulation of CPT1A and ACSL1 (p < 0.05). Molecular docking indicated favorable binding affinities between SIL and these targets, which was further supported by corresponding changes in protein expression via Western blotting. Correlation analysis revealed a consistent alignment between the upregulation of ACSL1/CPT1A and improvement in performance and antioxidant status, suggesting a coordinated metabolic shift. These findings emphasize the potential of SIL as a sustainable animal nutrition antioxidant additive, which can alleviate HS-induced lipid disorders in the liver of laying hens. Importantly, these hepatoprotective effects were demonstrated exclusively under chronic heat stress conditions; further studies incorporating a normothermic baseline are required to distinguish stress-specific mitigation from general metabolic stimulation. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. The updated terminology reflects a conceptual shift by emphasizing metabolic dysfunction rather than excluding alcohol consumption. This redefinition introduced MetALD, a subtype characterized by the coexistence of cardiometabolic risk factors and moderate alcohol intake. In the world, misclassification of MetALD as MASLD is frequent, often due to underreporting of alcohol consumption, which may distort epidemiological estimates. In Mexico, where both obesity and alcohol use are highly prevalent, this reclassification carries important implications for diagnosis, prognosis, and public health policy. This review summarizes the current evidence on MASLD and MetALD, highlighting their prevalence, diagnostic challenges, and implications for liver transplantation and cancer surveillance. We advocate for integrating these diseases into national non-communicable disease policies and adopting a multidisciplinary, preventive approach tailored to the Mexican context. Full article