Search Results (2,417)

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: Esophageal squamous cell carcinoma (ESCA) represents one of the most common aggressive malignancies worldwide. Insulin-like growth factor binding protein 1 (IGFBP1), a typical member of the IGF superfamily, is closely linked to adverse prognosis in numerous cancers. Up to now, little is known about its functional relevance to cell migration and tumor progression in ESCA. This work focuses on clarifying the relationship between IGFBP1 expression and the progression and migratory characteristics of ESCA. Methods: mRNA expression profiles from ESCA patients were obtained from the TCGA and GEO databases. Differential expression analysis was performed using R software(version 4.2.2), followed by an intersection of DEGs between datasets. The STRING database was applied to establish PPI networks. Cytoscape software(Version 3.7.2) was then used for visual presentation and hub gene identification. IGFBP1 expression was validated in ESCA tissues versus adjacent normal tissues. Prognostic correlation was assessed using GEPIA, while diagnostic and predictive values were evaluated through ROC analysis and Cox regression. Genetic alterations of IGFBP1 were analyzed via cBioPortal. Immune cell infiltration patterns were investigated using TIMER. Functional enrichment analyses (GO, KEGG) were performed on IGFBP1-associated DEGs. In the in vitro experiments, esophageal cancer cell lines (such as Eca109 and TE-1) and normal human esophageal epithelial cell lines (such as HEEC) were selected. The transcriptional level of IGFBP1 was examined using RT-qPCR, while Western blot analysis was conducted to validate its protein expression changes. Changes in the proliferative capacity of cancer cells after IGFBP1 silencing were detected by the CCK-8 assay, and cell migration capacity was determined via wound scratch assays to clarify the related biological effects. Results: Overall, 2870 DEGs were screened from the GEO database, 153 DEGs were screened from the TCGA database, and 34 genes were found to be common to both databases; 10 core genes were screened from the PPI network. IGFBP1 was abnormally expressed in esophageal cancer. Cox regression confirmed that IGFBP1 is an independent risk factor, and prognostic analysis indicated that IGFBP1 is closely associated with poor prognosis. Gene mutation analysis showed that amplification mutations are the most common type of IGFBP1 gene mutation, and genetic alterations in IGFBP1 in ESCA patients are significantly associated with overall survival (OS) (p = 0.0002568). GO analysis indicated that IGFBP1-related differentially expressed genes were enriched in organic anion transport, epidermal development, apical cell components, and metal ion transmembrane transporter activity. Pathway enrichment based on the KEGG database illustrated the main enrichment of target genes in neuroactive ligand–receptor interactions, calcium signaling and cAMP signaling pathways. Additionally, remarkable differences in immune cell infiltration were observed between IGFBP1 high-expression and low-expression subgroups through tumor immune profiling. IGFBP1 expression differed significantly between esophageal cancer cells and normal esophageal epithelial cells, as detected by RT-qPCR (p < 0.05). Moreover, knockdown of IGFBP1 markedly inhibited the proliferation (p < 0.05) and migration abilities (p < 0.05) of TE-1 and Eca109 cells. Conversely, IGFBP1 overexpression facilitated these cellular processes. Conclusions: As a key oncogenic driver for ESCA, IGFBP1 may participate in the oncogenesis of ESCA, possibly influencing clinical outcomes via IGF signaling and the tumor microenvironment. Its dual functions in tumor and immune systems suggest it might be a candidate for ESCA immunotherapy research. Full article

Objective: Insulin resistance is a key pathophysiological driver linking obesity and type 2 diabetes (T2D) with cardiovascular risk. Composite surrogate indices derived from routine clinical parameters, such as the Metabolic Score for Insulin Resistance (METS-IR) and the Single Point Insulin Sensitivity Estimator (SPISE), may provide a practical means of capturing multidimensional metabolic changes. Given that comparative data are limited, we aimed to evaluate the effects of sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on these indices in individuals with T2D and overweight or obesity. Methods: In this retrospective observational study, 100 individuals with T2D treated with either GLP-1RA (n = 54) or SGLT2i (n = 46) were evaluated over 6 months. Strict inclusion criteria ensured treatment stability without initiation or modification of concomitant pharmacotherapy. Changes in METS-IR and SPISE were assessed alongside body mass index (BMI) and glycated hemoglobin (HbA1c). Multivariable regression and exploratory analyses, including stratification by BMI and correlation analyses, were performed. Results: Both treatment groups demonstrated significant improvements in METS-IR (GLP-1RA: −3.9 ± 5.9; SGLT2i: −2.5 ± 2.6; both p < 0.001) and SPISE (GLP-1RA: +0.46 ± 0.52; SGLT2i: +0.44 ± 0.61; both p < 0.001), with no significant between-group differences. In the GLP-1RA group, changes in METS-IR correlated with changes in BMI (r = 0.48, p < 0.001) and HbA1c (r = 0.29, p = 0.030), whereas no significant correlations were observed in the SGLT2i group. Stratified analyses indicated greater reductions in METS-IR among individuals with BMI ≥30 kg/m² treated with GLP-1RA. Conclusions: Both SGLT2i and GLP-1RA improve composite surrogate markers of insulin resistance, with distinct associations with weight and glycemic changes. METS-IR and SPISE may serve as practical tools for monitoring multidimensional metabolic responses in clinical practice. Full article

Nogo (RTN4) proteins and their receptors have emerged as candidate mediators of metabolic regulation and vascular pathology relevant to type 2 diabetes (T2D). The primary objective of this PRISMA-guided systematic review was to evaluate the clinical and cohort evidence for RTN4/RTN4R as potential biomarkers of T2D progression and vascular complications. A secondary objective was to synthesize preclinical mechanistic evidence on the effects of Nogo axis modulation on pathways relevant to the pathogenesis of T2D. We performed a PRISMA-guided systematic review. The protocol was not prospectively registered in PROSPERO. To ensure reproducibility, we provide complete search keywords, the screening log and the full-text exclusion table. PubMed/MEDLINE, EMBASE and Web of Science were searched for studies published 2000–2025; full search keywords are provided in the main text. The search strategy combined and free-text terms with Boolean operators. We included original preclinical and clinical studies, cohort/proteomic analyses, meta-analyses, and mechanistic papers reporting expression, function, signaling, or clinical associations of Nogo proteins/receptors in metabolic or vascular outcomes. Exclusion criteria: non-English articles, unclear methods, studies outside 2000–2025, and studies lacking primary data. Two reviewers independently screened records; conflicts were resolved by consensus. Study quality was appraised using established tools (SYRCLE for animal studies, Newcastle–Ottawa Scale for cohort/case-control studies). Preclinical evidence supports tissue-specific roles for RTN4 isoforms and receptors in the regulation of insulin secretion, proGCG → GLP-1 processing, ER homeostasis, and vascular permeability through the Src/PI3K/Akt and RhoA/ROCK axes. Cohort and proteomic analyses report associations between RTN4/RTN4R or serum NogoB and faster progression of T2D or vascular complications, but genetic assessment of causality (Mendelian randomization) has so far provided limited support in available data sets. Findings are heterogeneous with respect to directionality and tissue localization. RTN4 signaling exhibits tissue-specific mechanisms relevant to glucose regulation and vascular biology and warrants further translational study. However, heterogeneity across studies and limited genetic support for causality indicate that isoform-specific quantitative validation, longitudinal cohorts and integrated genetic–functional analyses are required before RTN4/RTN4R can be considered as clinical biomarkers. Full article

Background: The pharmacological management of type 2 diabetes mellitus has become increasingly complex due to expanding therapeutic options and the high prevalence of multimorbidity in affected patients. As a result, the risk of drug–drug and drug–disease interactions has grown significantly, with potential implications for glycemic control, safety, and treatment outcomes. Objective: This narrative review provides a comprehensive, class-based overview of clinically relevant interactions associated with antidiabetic medications, highlighting their mechanisms, clinical consequences, and practical management strategies. Methods: A targeted literature search was conducted using major medical databases to identify clinical studies, meta-analyses, pharmacovigilance reports, and evidence-based guidelines concerning interactions related to key antidiabetic drug classes. Interactions were categorized as pharmacokinetic, pharmacodynamic, or disease-related. Results: Significant variability exists across antidiabetic drug classes in terms of interaction profile and clinical relevance. Metformin presents interaction risks mainly through renal impairment or co-administration with drugs affecting lactate metabolism. Sulfonylureas and glinides are strongly associated with hypoglycemia-enhancing interactions. DPP-4 inhibitors generally exhibit a low interaction burden, whereas GLP-1 receptor agonists may interact through delayed gastric emptying. SGLT2 inhibitors require caution in patients with diuretics or conditions predisposing them to dehydration or ketoacidosis. Insulin remains highly sensitive to pharmacodynamic interactions with a broad spectrum of therapies. Underlying renal, hepatic, and cardiovascular conditions further modify the interaction risk. Conclusions: Understanding class-specific interaction profiles is essential for personalized and safe diabetes management. Careful medication review, close metabolic monitoring, and individualized dose adjustments can mitigate the risk of harmful interactions. Further research is needed to elucidate interactions in populations with advanced multimorbidity and polypharmacy. Full article

Background: Dietary protein optimization is an important nutritional strategy for improving growth and physiological responses, and antioxidant homeostasis in fish. Methods: In this study, 540 black carp (initial body weight: 10.50 ± 1.00 g) were randomly assigned into recirculating tanks (500 L) fed with six dietary protein levels (30–44% crude protein) for an 8-week feeding trial with triplicates per treatment and 30 fish per replicate. After the trial, fish body, blood, hepatopancreas, and intestinal samples were collected for body composition, serum biochemical parameters, metabolism, and antioxidant indices’ analyses. Results: Results showed fish fed 38% protein (PT38) exhibited the highest weight gain (p < 0.05), with no further improvement at higher protein levels. Compared with PT30 group, PT38 group significantly promoted protein deposition by upregulating transcript levels of insulin-like growth factors (IGFs) via activating mechanistic target of rapamycin (mTOR) signaling pathway. PT38 could improve fatty acid oxidation by heightening levels of carnitine palmitoyl transferase 1α (CPT1α), peroxisome proliferator-activated receptor α (PPARα) and PPARδ. Meanwhile, PT38-PT41 significantly inhibit expression of fatty acid synthesis and lipid droplet deposition-related genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and perilipin 2 (p < 0.05). PT38 significantly enhanced antioxidant homeostasis by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Conclusions: Overall, Under the current experimental conditions, 38% dietary protein is suitable for promoting growth performance, improving protein and lipid metabolism, and enhancing antioxidant homeostasis in black carp. Full article

Background: Metabolic-associated fatty liver disease (MAFLD) has a high prevalence of 30–40% in China and Asia, with a complex pathogenesis and no specific therapeutic drugs. Phytochemicals have become a research hotspot for MAFLD prevention, and ginsenosides, the core active components of Panax ginseng, show great potential in anti-MAFLD research. This review aims to comprehensively clarify the key mechanisms and targets of ginsenosides in preventing and treating MAFLD, to provide a theoretical basis for their application in metabolic diseases, and to promote the development of natural phytochemical resources. Method: The literature review method was adopted to sort out the regulatory effects and molecular targets of ginsenosides in multiple pathological processes of MAFLD from published studies. Results: Ginsenosides regulated MAFLD through multi-pathway and multi-target effects: antioxidant regulation occurred via Nuclear factor E2-related factor 2 (Nrf2)/Silent information regulator 1/6 (SIRT1/6) pathways, and anti-inflammatory regulation was achieved by inhibiting the Nuclear factor kappa-B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Additionally, the measures adopted improved insulin resistance and lipid metabolism disorder, suppressed hepatocyte apoptosis/pyroptosis, repaired autophagy, alleviated hepatocyte senescence, and reshaped gut microbiota to restore gut–liver axis homeostasis. Conclusions: Ginsenosides have good potential for MAFLD prevention and treatment, but there is a prominent lack of human clinical evidence as most existing studies are only based on in vitro cell and in vivo animal models, and the synergistic mechanisms among different ginsenoside components remain unclear. Future research needs multi-omics analysis, formulation optimization, and large-sample clinical trials, and ginsenosides have broad application prospects in MAFLD intervention. Full article

Obesity is a growing public health concern linked to poor dietary habits, physical inactivity, and metabolic disturbances, which can be evaluated using complementary laboratory tests. Among pharmacological interventions, semaglutide, a GLP-1 receptor agonist, has shown promise by acting on the central nervous system to reduce appetite and stimulate insulin secretion, thereby improving the lipid profile and reducing inflammation biomarkers. This review focused on changes in lipid parameters and C-reactive protein (CRP) levels in overweight or obese individuals treated with semaglutide, based on phase 3 studies from the STEP program (“Semaglutide Treatment Effect in People with Obesity”). The STEP clinical trial program was conducted across 36 countries, reflecting a broad and diverse geographic representation. Key findings include significant reductions between placebo vs. semaglutide in body weight (−1.3 vs. −13.0 Kg), body mass index (−0.69 vs. −4.72 kg/m²), and waist circumference (−2.79 × −11.81 cm). Additionally, there were notable decreases in triglycerides (−0.67 vs. −20.89%), VLDL-C (−0.99 vs. 20.82%), and CRP levels (−15.45 vs. −55.55%). These changes reflect improvements in both inflammatory and metabolic markers. The observed benefits suggest that semaglutide may contribute to reducing comorbidities associated with metabolic syndrome and to the prevention of cardiovascular disease. Current evidence also supports its potential role in individualized treatment strategies based on patients’ clinical and biochemical profiles. However, despite these promising findings, further long-term studies are required to confirm the efficacy and safety of semaglutide across diverse populations. Full article

Background: Cancer-associated cachexia (CAC) is a multifactorial syndrome driven by a profound metabolic and inflammatory dysregulation. Due to the central role of the insulin-like growth factor 1 (IGF-1) pathway in regulating muscle mass, energy metabolism, and inflammation, this study evaluated the relevance of five IGF-1 axis-related single-nucleotide polymorphisms (SNPs), namely IGF1 rs6220, insulin-like growth factor 1 receptor (IGF1R) rs2016347 and rs2684788, growth hormone receptor (GHR) rs6873545, and insulin receptor substrate 1 (IRS1) rs1801278. Methods: The impact of these variants on CAC onset and overall survival (OS) was assessed in a cohort of 140 cancer patients. Results: While overall-cohort analyses did not reach statistical significance, exploratory analyses suggested potential associations between the IGF1 rs6220 GG and GHR rs6873545 CC genotypes and increased CAC risk in male patients. A trend for higher CAC prevalence was also noted in younger patients (<63 years) with the rs6873545 CC genotype. For pre-CAC and CAC patients, exploratory subgroup analyses on patients’ OS were conducted following no significant results in the overall cohort. Among older patients and those with high prognostic nutritional index (PNI; >44.2), the IGF1 rs6220 G allele was associated with longer OS. Conversely, the IGF1R rs2016347 G allele and rs2684788 T allele were linked to poorer OS across multiple pre-CAC and CAC subgroups. The effects of GHR rs6873545 varied across subgroups, suggesting context-dependent activity. Conclusions: This study highlights the functional heterogeneity of IGF-1 axis-related genetic variants, indicating potential to serve as predictors of CAC. Given the exploratory nature of these findings, validation in larger cohorts is required to confirm the associations found. Full article

Insulin-like growth factor 1 (IGF-1) signaling plays a complementary role to insulin signaling in glucose metabolism homeostasis. This study characterized the physiological roles of the IGF1 receptor A (Igf1ra) and B (Igf1rb) in zebrafish. The transcripts of igf1ra and igf1rb were detected in multiple zebrafish tissues, including the liver, muscle, and brain. Zebrafish lacking igf1ra or igf1rb were generated using CRISPR/Cas9 technology. Both igf1ra^−/− and igf1rb^−/− zebrafish exhibited stunted growth. Reduced BMI was found in igf1ra^−/− zebrafish, while BMI increased in igf1rb^−/− zebrafish. Hyperglycemia and increased hepatic glycogen were observed in igf1ra^−/− zebrafish, while blood glucose levels in igf1rb^−/− zebrafish were normal. No significant difference in whole-body or hepatic triglyceride content was observed in igf1ra^−/− zebrafish, while the whole-body and hepatic triglyceride content of igf1rb^−/− zebrafish increased compared to their wild-type control siblings. Further analyses of the expression patterns of key genes involved in glucose and lipid metabolism were conducted on igf1r mutants. Decreased levels of genes involved in glucose absorption and glycolysis and increased levels of genes involved in gluconeogenesis and glycogen synthesis were observed in igf1ra^−/− zebrafish, but not in igf1rb^−/− zebrafish. Conversely, significantly decreased levels of transcripts involved in lipolysis and increased levels of transcripts involved in the lipogenesis process were observed in igf1rb^−/− zebrafish, but not in igf1ra^−/− zebrafish. Restricted cell growth and protein synthesis signaling, including AKT and mTOR activation, was also detected in igf1ra^−/− zebrafish, while a moderate elevation in AKT and mTOR activity was seen in igf1rb^−/− zebrafish. Taken together, our results suggest that functional divergence occurred after the duplication of the zebrafish igf1r gene, with igf1ra primarily modulating glucose absorption and utilization, and igf1rb primarily affecting lipid metabolism in the somatotropic axis. Full article

The renin–angiotensin system (RAS) regulates inflammation, tissue homeostasis, and barrier integrity in lung and colon epithelial cells. Beyond classical pathways, non-canonical components including angiotensin-converting enzyme 2 (ACE2), epidermal growth factor receptor (EGFR), insulin-like growth factor 2 receptor (IGF2R) and aminopeptidase N (ANPEP) are implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and bacterial sepsis due to their roles in tissue repair and signaling. Despite their similar inflammatory and coagulopathic features, their impact on RAS-associated non-immune gene expression in epithelial tissues remains unclear. This study investigates the regulation of these targets in lung (BEAS-2B) and colon (CRL-1831) cells following exposure to recombinant SARS-CoV-2 spike protein N-terminal domain fragment (S1-NTD) and Pseudomonas aeruginosa-derived lipopolysaccharide (LPS). Cells were treated with 100 ng/mL of S1-NTD or LPS for 12–72 h. Viability was assessed via XTT assays, and molecular changes were analyzed through qRT-PCR and Western blotting. Both stimuli induced a time and dose-dependent decrease in metabolic activity. ACE2 was significantly downregulated in lung cells, while transient upregulation occurred in colon cells at 24 h. EGFR expression increased in colon cells following LPS exposure but decreased in lung cells after S1-NTD treatment. Both IGF2R and ANPEP were upregulated by S1-NTD in lung cells at 72 h, whereas colon cells showed earlier upregulation at 24–48 h. Our findings reveal that viral and bacterial stimuli elicit distinct, tissue-specific regulatory patterns in RAS-associated pathways. These alterations may contribute to epithelial barrier dysfunction and inflammation, highlighting these proteins as potential targets for managing secondary bacterial infections and inflammatory lung–gut complications in COVID-19. Full article

Objectives: The study aimed to evaluate the effects of full-fat rice bran (FFRB; Tainung No. 81, Taiwan) at various doses on insulin resistance, muscle atrophy, and gut microbiota composition in middle-aged ovariectomized (OVX) mice fed a high-fat diet (HFD), using young sham-operated mice as a life-stage reference group. Methods: Thirty-six female ICR mice were assigned to six groups, including OVX mice fed HFD with or without 5%, 10%, or 20% FFRB. Results: Compared with HFD-fed OVX controls, 20% FFRB reduced body weight gain by 43%, decreased visceral fat mass, and improved insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR reduced by 65%, P_trend = 0.001). FFRB attenuated the decline in relative grip strength (forelimb, P_trend = 0.013; four-limb, P_trend < 0.001), and upregulated muscle protein synthesis genes, including insulin receptor substrate 1 (IRS-1), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E binding protein 1 (eIF-4EBP1), while downregulating forkhead box protein O1 (FOXO1), muscle RING-finger protein-1 (MuRF-1), and interleukin (IL)-6. FFRB was also associated with higher fecal acetate levels (P_trend < 0.001), upregulated colonic tight junction genes (occludin and zonula occludens (ZO)-1), and greater relative abundance of g_Muribaculum. Correlation analyses revealed positive associations between short-chain fatty acids (SCFAs) and muscle strength, muscle anabolic markers, genus Lachnospiraceae_UCG_001, and Muribaculum. Conclusions: Dietary inclusion of FFRB was associated with favorable metabolic and muscle-related parameters in HFD-fed middle-aged OVX mice, with potential involvement of gut microbiota and SCFA alterations. Full article

This review aims to comprehensively examine spent coffee grounds (SCGs) as a sustainable source of antioxidant and immunomodulatory bioactives, with a specific focus on their capacity to modulate membrane-level signaling through ion channels and G-protein-coupled receptors (GPCRs) in the context of lifestyle-related chronic diseases. SCGs, the major solid by-product of coffee brewing, represent an underutilized yet highly abundant source of bioactive compounds, including chlorogenic acids, phenolic acids, melanoidins, diterpenes, and residual alkaloids. Lifestyle-related chronic diseases, including type 2 diabetes, obesity, cardiovascular disease, and chronic inflammatory disorders, are increasingly recognized as immunometabolic conditions driven by persistent low-grade inflammation, redox imbalance, and dysregulated membrane signaling. This review synthesizes current evidence demonstrating that bioactives contained in SCG extracts exert antioxidant and immunomodulatory effects that extend beyond radical scavenging. Crucially, these compounds also act as modulators of membrane-level signaling, representing a mechanistic perspective that has not been previously integrated for SCGs in the context of chronic disease. The different extraction methodologies and the obtained results are evaluated with the aim to identify the most effective experimental approach and extraction conditions. The paper also discusses how SCG compounds regulate redox-sensitive ion channels (including calcium channels, TRP channels, and potassium channels), and key GPCR pathways (such as GPR120, GPR43, and adenosine receptors), thereby influencing immune cell activation, cytokine production, insulin signaling, and metabolic inflammation. Particular attention is given to the role of microbial fermentation and enzymatic processing in enhancing SCG bioavailability, generating postbiotic metabolites that further engage GPCR–ion channel crosstalk. By integrating extraction approaches, antioxidant chemistry, immunology, membrane signaling, and nutritional metabolism, this review positions SCG as a sustainable functional ingredient capable of restoring immune tolerance and metabolic homeostasis. These insights support the valorization of SCGs within the circular economy framework and highlight their potential application in next-generation immunonutrition strategies for chronic disease prevention and management. Full article

The global burden of type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise at an alarming pace, with substantial pathophysiological overlap driven by insulin resistance, visceral obesity, and chronic low-grade inflammation. MASLD may progress to metabolic dysfunction-associated steatohepatitis (MASH), with increased risk of cirrhosis and hepatocellular carcinoma. Glucagon-like peptide 1 (GLP-1)-based therapies have transformed the management of T2DM and obesity. They exert pleiotropic effects whose basis remains incompletely understood. Concurrently, Akkermansia muciniphila has emerged as a keystone gut microbiota species with demonstrated hepatoprotective potential in preclinical models of MASLD/MASH. This narrative review positions A. muciniphila simultaneously as a target of GLP-1-mediated microbiome remodeling and as an independent modulator of hepatoprotection in MASLD/MASH. A structured search of PubMed, Scopus, and Web of Science (last searched: 12 April 2026) was conducted using terms related to Akkermansia muciniphila, GLP-1 receptor agonists, MASLD/MASH and T2DM. A total of 174 records were identified. Of these, 148 were excluded due to duplication or non-relevant study design. 26 studies (23 preclinical, 3 clinical) were included in the synthesis, directly addressing A. muciniphila. Preclinical evidence demonstrates that liraglutide, semaglutide, exenatide, and tirzepatide increase A. muciniphila abundance, while A. muciniphila in turn enhances endogenous GLP-1 secretion via the P9/ICAM-2 axis, forming a hypothetical positive feedback loop. A working mechanistic model integrating these bidirectional interactions is proposed, alongside a discussion of current limitations and future research priorities, including microbiome-guided clinical trials in MASLD/MASH populations. Full article

Background: Effective postprandial glycemic regulation is essential for preventing metabolic disorders such as type 2 diabetes. While pharmacological interventions like GLP-1 (Glucagon-Like Peptide-1) receptor agonists are effective, dietary strategies using low-digestible carbohydrates (LDCs) may offer a sustainable and complementary approach. Methods: Two human physiological investigations were conducted to evaluate the acute metabolic responses to allulose, 1-kestose, resistant maltodextrin (RD), and fructo-oligosaccharide powder (FOP), administered both in isolation and in conjunction with a reference meal (RM). Results: In Study 1, all tested LDCs elicited minimal plasma glucose responses when consumed alone. In Study 2, distinct metabolic benefits were observed depending on the type of LDCs. Allulose exhibited the strongest effects, significantly reducing postprandial glucose and insulin levels while increasing plasma GLP-1 concentrations. 1-Kestose exhibited significantly lower plasma glucose and insulin incremental area under the curve (iAUC) compared to RM alone, indicating improved glycemic regulation. RD significantly enhanced subjective satiety between 30 and 180 min post-consumption. These findings highlight that each LDC exerts unique physiological effects. Conclusions: Collectively, these results demonstrate that acute LDCs consumption distinctly regulates metabolic responses, supporting their application as functional ingredients in targeted nutritional strategies for managing glycemic and metabolic health. Full article