Cancer remains one of the leading causes of mortality worldwide, with its progression intimately linked to complex intercellular communication networks within the tumor microenvironment. Exosomes are nanoscale extracellular vesicles (EVs) of endosomal origin acting as active mediators of intercellular communication. Importantly, exosomes have emerged as critical mediators of intracellular communication that can influence microenvironmental homeostasis by transferring their bioactive cargo including proteins, lipids, and nucleic acids between cells. Although exosomes are the best-characterized miRNA carriers, other EV subclasses, including plasma membrane-derived microvesicles, apoptotic bodies, large oncosomes and migrasomes, also convey miRNAs and modify recipient cell behavior, and are therefore considered here alongside exosomes. We further examine mitochondria-derived vesicles (MDVs), a distinct vesicular pathway that connects mitochondrial quality control to the endosomal compartment and that may act upstream of exosomal miRNA loading. Among their cargo, exosome-derived microRNAs (exomiRs) have attracted considerable attention for their ability to negatively regulate gene expression in recipient cells, modulating key oncogenic processes such as angiogenesis, invasion, immune evasion, epithelial-to-mesenchymal transition, drug resistance, and cancer-related stem cell activity. This review aims to synthesize current knowledge on the biogenesis and function of EVs, including exosomes and MDVs, and of exomiRs linked with carcinogenesis and specifically addresses emerging evidence supporting pharmacological and nutraceutical interventions to modulate exomiR profiles as a novel chemopreventive strategy. We further discuss how diet-derived nutraceuticals, including plant polyphenols and isoflavones, can alter the microRNA expression landscape in cancer cells and their secreted exosomes, and we provide a global, cross-study overview of the miRNAs reported to respond to phytochemical exposure. In addition, we discuss the potential consequences of these modulations in several key carcinogenesis-associated processes such as angiogenesis, inflammation, oxidative stress, and stem cell mobilization. While direct targeting of exomiRs remains technically challenging, recent reports support the hypothesis that intracellular miRNA modulation may propagate to the exosomal compartment, thereby influencing intercellular communication. Collectively, this evidence highlights microRNA modulation as an indirect yet promising strategy to influence exosome-mediated intercellular communication in cancer and provides a conceptual framework for understanding exomiRs as a programmable layer of tumor-associated signaling. MicroRNA modulation by nutraceuticals and drugs may extend to the exosomal compartment. Exosome-associated miRNAs (exomiRs) are proposed as a dynamic interface of intercellular signaling. Emerging evidence suggests that intracellular microRNA levels alter the exosomal cargo composition, and that EV subclasses other than exosomes also convey miRNAs. Mitochondria-derived vesicles (MDVs) and mitochondrial stress may act as upstream regulators of exosomal signaling. Modulating miRNAs affects multiple signaling pathways that, in turn, indirectly reshape tumor microenvironment communication.
An Arctic-specific loss-of-function variant in the gene encoding sucrase-isomaltase (SI) results in the inability to digest sucrose in homozygous carriers, and also a healthier cardiometabolic phenotype. Importantly, the specific impact of the SI variant on food intake and preferences has not been studied in detail. We compared 18 homozygous SI-carriers with 20 non-carriers from Greenland matched on sex, age, BMI, and Inuit genetic ancestry. We assessed food intake using a semi-quantitative food frequency questionnaire and an ad libitum free-choice test meal. We assessed food reward using the Leeds Food Preference Questionnaire as well as participants’ ability to discriminate between sucrose and other sugars and sweetness/liking ratings in a sensory test. In the sensory test, carriers rated liking of sucrose and fructose significantly lower than non-carriers on a 100 mm visual analogue scale (−26 mm, p = 0.001 and −13 mm, p = 0.04, respectively). When comparing sucrose with fructose+glucose for most sweet and most liked sample, choice of sample was not associated with genotype. In the Leeds Food Preference Questionnaire, carriers expressed higher explicit liking and wanting for low-fat savoury foods than non-carriers (p = 0.04 and p = 0.01, respectively) as well as a lower explicit liking for high-fat foods relative to low-fat foods compared to non-carriers (p = 0.01). No significant differences were observed for the remaining food reward outcomes. Nutrient composition of the habitual diet and of the ad libitum test meal was overall similar in the two genotype groups. However, half of the carriers reported avoiding foods high in sugar compared to none of the non-carriers and habitual energy intake from high-fat sweet foods was 66
Hyperuricemia(HUA) is associated with metabolic and cardiovascular comorbidities. Genetic factors, particularly the ABCG2 rs2231142 polymorphism, and dietary habits such as vegetarianism, significantly influence hyperuricemia risk. However, the interplay between these factors remains unclear in the Taiwanese population. To investigate the association of the ABCG2 rs2231142 polymorphism and vegetarian diet on the risk of hyperuricemia in a Taiwanese cohort. This population-based case-control study utilized data from 11,113 participants in the Taiwan Biobank. Participants carrying the ABCG2 rs2231142 polymorphism (GG and GT/TT genotypes) were analyzed alongside dietary habits (vegetarian vs. non-vegetarian) and various clinical confounders. Logistic regression was used to calculate odds ratios (ORs) and identify gene–diet interactions. Among 11,113 participants, the overall prevalence of HUA was 11.1
Metabolic syndrome (MetS) is a global health issue linked to increased disease risk and economic burden. Traditional biomarkers for MetS reflect disrupted homeostasis but may fail to detect earlier stages of imbalance, i.e., an increase in allostatic load. Health can be defined as the capacity to maintain or recover homeostatic control, and this capacity can be assessed via a standardized nutritional challenge test (e.g., PhenFlex), which provokes adaptive metabolic responses. We aimed to identify a biomarker signature indicative of MetS-associated allostatic load, using data from multiple nutritional challenge test (NCT) studies. A multi-study analysis was performed using data from four human studies with nutritional challenge test (n = 195). We identified 64 analytes with significantly altered postprandial responses in individuals with MetS (n = 78) compared to healthy controls (n = 117). Cluster analysis revealed four clusters with a distinct temporal dynamic response to the NCT. The most prominently affected analytes included total triacylglycerides, C-peptide, leptin, and a range of amino acids (e.g., L-glutamic acid, L-serine, and L-leucine). The response of a subset of these analytes to the nutritional challenge test also changed after a 12-week, 20
Dietary choices influence both risk and development of type 2 diabetes (T2D), but the precise mechanisms remain incompletely described. Dietary intake and lifestyle behaviors can alter epigenetic states with subsequent modulations on gene expression which then can change the risk of T2D. An epigenome-wide association study was conducted to identify any epigenetic links to diabetes risk by investigating epigenetic changes during a 6-year follow-up in 374 participants who were free of T2D at baseline. The identified epigenetic changes were examined for their association with any dietary and lifestyle factors. Additionally, mediation analysis determined whether the associated dietary factors contribute to diabetes risk through epigenetic changes. The epigenome-wide association study identified significant epigenetic changes during the 6-year follow-up at seven loci within genes REPIN1, BMP2, LINC01723, and SEL1L2, all of which were associated with insulin resistance. Further analysis revealed strong associations between three specific differentially methylated sites (DMSs) cg16400647 in REPIN1, cg12344389, and cg00625573, and dietary vitamin B12 intake. Additionally, cg26719314 on the X chromosome showed separate robust correlations with total sugar intake. Mediation analysis showed that higher vitamin B12 intake might reduce insulin resistance through epigenetic modification in REPIN1 and DNAAF9. Conversely, higher total sugar intake correlated significantly with elevated diabetes risk, with cg26719314 acting as a mediator. Furthermore, increased vitamin B12 supplementation was associated with decreased insulin resistance at 6-year follow-up in the entire cohort. These findings suggest that vitamin B12 intake may influence insulin resistance through specific epigenetic changes, thus describing the epigenetic links between diet and development of T2D.
Obesity is associated with metabolic dysfunction-associated steatotic liver disease (MASLD), for which drugs and nutraceuticals are being developed. We investigated whether camelina seeds from the Brassicaceae family and their components can attenuate metabolic disorders in animal models of genetic obesity, including fatty liver. In two separate 5-week experiments, female obese (fa/fa) Zucker rats and female db/db mice were used. By appropriately incorporating camelina seeds or their oil into the diet, we investigated, in the rat model, the effects of the oil and non-oil fractions on intestinal and liver function, as well as on lipid metabolism. Subsequently, in a mouse model, oral administration of glucocamelinin, the main camelina glucosinolate, was performed to determine whether this group of compounds might be responsible for the observed beneficial effects. Dietary camelina seeds counteracted liver hypertrophy and steatosis in obese rats, as confirmed by macroscopic and histological images, along with a several-fold lower content of total fat, triglycerides, and cholesterol (p < 0.01 for each). The rat experiment indicated that the non-oil fraction of camelina seeds was responsible for these beneficial effects. Oral glucocamelinin attenuated liver hypertrophy and steatosis in obese mice, as confirmed by macroscopic and histological images, along with considerably lower total fat (p < 0.05) and cholesterol (p < 0.01) contents. In both obese rats and mice, these and other beneficial effects were associated with alterations in the hepatic expression of genes crucial to lipid and glucose metabolism, including a higher expression of those encoding thyroid hormone receptor β (THR-β; p < 0.01 and p < 0.05) and fibroblast growth factor 21 (FGF21; p < 0.01 and p < 0.05). These findings indicate that camelina seeds may be considered both a dietary component and a source of bioactive glucosinolates relevant to MASLD. The mechanism behind the lipid-lowering effect of glucocamelinin may involve hepatic activation of FGF21 signaling through THR-β.
Nutrient-gene interactions are key determinants of metabolic disease phenotypes, but systematic analysis remains constrained by the labour required to generate precisely defined diets. To address this, we developed a flexible method for assembling synthetic diets for Drosophila melanogaster from individual stock solutions, enabling rapid and controlled modification of dietary composition. Using this approach, we generated a rational array of 51 diets in which single nutrients were varied systematically. We first showed that diets prepared using the flexible method performed comparably to standard preparation methods in wild-type flies, with similar developmental timing, survival, adult body weight, and starvation resistance. As a proof-of-concept, we then applied this dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe metabolic disorder caused by defective sulfur amino acid catabolism. This validated previously identified nutrient-specific effects, including survival and pupariation rescue by cysteine depletion, while also revealing additional amino acid-modified diets that improved pupal survival. This platform provides a scalable and versatile in vivo framework for systematically interrogating genotype-specific nutritional responses in Drosophila. It should facilitate the identification of diet-gene interactions relevant to metabolic disease and support broader nutritional screening across disease models.
BACKGROUND:Recent studies have demonstrated that vitamin D (VD) influences gut microbiota (GM) by regulating epithelial barrier function and immune responses, thereby affecting microbial composition and diversity. Additionally, host genetic factors, particularly single-nucleotide variants (SNVs) in genes related to VD metabolism, may influence GM composition. Postmenopausal women are a particularly relevant population to assess the impact of these SNVs, as this group experiences reduced hormonal variability and a higher burden of vitamin D deficiency (VDD), enabling clearer evaluation of the association between vitamin D-related genetic variants and gut microbiota composition. OBJECTIVE:To explore the relationship between SNVs in genes involved in VD metabolism and their impact on GM. METHODS:We genotyped nine variants: rs10741657 (CYP2R1), rs6013897 (CYP24A1), rs10877012 (CYP27B1), rs10783219 and rs4516035 (VDR), rs4588 and rs7041 (GC), rs4944957 and rs3794060 (NADSYN1). GM was characterized by sequencing the V4 hypervariable region of the 16S rRNA gene. We compared taxon abundance at the genus level across host genotypes using the dominant model. Quantile regression was used to analyze non-mean diversity responses, and PICRUSt2 identified functional pathways. We also calculated the genetic risk score (GRS) using rs4516035, rs3794060, and rs4944957, which were associated with lower alpha diversity. RESULTS:Alpha microbial diversity differed significantly for the VDR (rs4516035) and NADSYN1 (rs3794060, rs4944957) variants, both for risk alleles and genotypes. Differential abundance analysis identified taxonomic disparities, notably in the genera DTU014, Fusobacterium, Negativibacillus, Pseudomonas, Peptococcus, and [Clostridium]_innocuum_group. PICRUSt2-predicted functional pathways for the rs4516035- C allele revealed significant glutamine-glutamate, folate, galactose, and fatty acid metabolism. A GRS was associated with lower alpha diversity indices and differences in the insulin signaling pathway and oxidative phosphorylation. CONCLUSIONS:These findings highlight the role of SNVs in GM modulation and suggest potential implications for VD metabolism and host health.
Background Zinc deficiency remains a major global health concern and disproportionately affects populations in regions such as sub-Saharan Africa. Although inadequate dietary intake is a primary determinant of zinc status, genetic variation in zinc transport pathways may contribute to interindividual and interpopulation differences in zinc utilization. The SLC39A10 gene encodes the zinc importer ZIP10, which is upregulated under zinc-restricted conditions to sustain cellular zinc acquisition. This study sought to identify functional SLC39A10 variants and evaluate their potential physiological relevance, with particular attention to alleles enriched in populations of African ancestry. Methods and results Missense variants in SLC39A10 were identified through analysis of sequencing data from the Genome Aggregation Database. The three most frequent minor alleles were markedly enriched in populations of African ancestry. Among these, two histidine-replacing variants, H194Q and H609Y, located near conserved histidine-rich regions of ZIP10, exhibited reduced capacity to increase cytosolic labile zinc levels and metallothionein expression in HEK293T cells, consistent with hypomorphic effects on transporter activity.These functional differences were not attributable to altered transcript abundance, protein expression, or subcellular localization. In silico variant effect prediction and evolutionary conservation analyses further supported the functional relevance of these substitutions. Phenome-wide association analyses in a large African ancestry cohort revealed nominal associations of these variants with hematologic and renal traits, suggesting potential physiological consequences of altered zinc transport capacity. Conclusions These findings identify SLC39A10 as a locus of nutrigenetic diversity and demonstrate ancestry-linked variation in cellular zinc handling. The characterization of African-enriched hypomorphic ZIP10 variants provides mechanistic insight into genetic influences on micronutrient homeostasis. Incorporating genetic variation in zinc transport pathways may improve precision nutrition strategies and inform public health approaches aimed at reducing population-specific vulnerability to zinc deficiency.
Background Personalized nutrition (PN) interventions are increasingly used to address overweight and obesity, yet randomized controlled trials (RCTs) vary widely in how personalization is defined and delivered. This scoping review synthesized methodological characteristics of PN RCTs in adults with overweight or obesity and meta-analyzed PN effects on anthropometrics. Main text We searched PubMed, Scopus, Web of Science, and ClinicalTrials.gov through November 20, 2025. Data were extracted using a standardized template capturing intervention characteristics. A random-effects meta-analysis was conducted, Bayesian meta-regression was used to explore the effect of intervention duration, and certainty of evidence was evaluated using GRADE. Among the 17 included RCTs, none provided a definition of PN, and substantial methodological heterogeneity was evident. Personalization inputs differed markedly in both number and type, and delivery modes ranged from digital platforms and group sessions to meal-box provision and routine dietitian consultations. PN interventions typically used the same delivery format as their control groups but layered on individualized components, with some providing higher contact frequency. Comparator structures also varied, from standardized guideline-based diets to minimal or no dietary counseling. Personalized diets were produced through algorithmic models, dietitian-guided tailoring, or continuous glucose monitoring-guided participant selection. PN produced a small but significant reduction in body weight, while effects on body mass index (BMI) were non-significant. Longer intervention duration was credibly associated with greater reductions in body weight and BMI. No publication bias was detected, and certainty of evidence was low for body weight and very low for BMI. Conclusions PN interventions show modest effects on body weight but not BMI, within a highly heterogeneous methodological landscape. This review identifies design features to guide more effective PN interventions. Advancing toward more standardized approaches will require clearer operational definitions of personalization, better-aligned comparator diets, and greater transparency in how personalized strategies are generated and delivered.
The effects of caloric restriction (CR) during active colitis remain incompletely understood. We examined whether short-term CR, initiated during dextran sodium sulfate (DSS)-induced inflammation, modulates disease severity, host transcriptional responses, and gut microbiota composition. Cross-species transcriptomic analyses were used to contextualize these effects within established human ulcerative colitis (UC) signatures. Male C57BL/6 mice were assigned to control, CR, DSS, or DSS with concurrent CR (DSS.CR) groups. Clinical disease activity, histopathology, hematology, anxiety-like behavior, colon and spleen transcriptomes (RNA-seq), and fecal microbiota (16S rRNA) were assessed. Public UC microarray datasets were used to compare DSS and DSS.CR transcriptional profiles with human active and inactive UC. Compared with DSS, DSS.CR mice showed modest but consistent improvements in stool consistency and bleeding, with limited effects on overall histopathological scores, and reduced splenic enlargement and disruption. Transcriptomic analysis revealed limited differential gene expression between DSS and DSS.CR, but gene set enrichment analysis indicated reduced activation of inflammatory pathways (e.g., NF-κB, IL-17, cytokine–cytokine receptor) and relative enhancement of epithelial renewal and proteostasis programs. CR also partially mitigated DSS-associated dysbiosis, modestly preserving microbial diversity and functional pathways linked to carbohydrate metabolism and detoxification. Human microarray meta-analyses confirmed that DSS recapitulates active UC signatures, while CR shifted these toward a remission-like profile. Short-term CR during acute DSS-induced colitis partially attenuated mucosal and systemic inflammation and modestly shifted transcriptional and microbial profiles toward epithelial repair and metabolic resilience. These findings highlight CR’s potential as a non-pharmacological adjunct for modulating intestinal inflammation and support further translational evaluation of feasible dietary restriction strategies in IBD.
Oxidative stress is a key driver of sperm DNA fragmentation (SDF), a molecular defect increasingly identified in men with idiopathic infertility, even when standard semen parameters appear normal. Dietary carbohydrate quality and glycemic properties may modulate oxidative stress, but their relationship with sperm DNA integrity remains underexplored. To examine the association between dietary glycemic index (GI), glycemic load (GL), carbohydrate quality index (CQI), and low-carbohydrate diet score (LCDS) with the odds of elevated sperm DNA fragmentation index (DFI) in men with unexplained infertility. In this case-control study, 300 Iranian men aged 18–50 years (150 with DFI > 30
Gene-based nutrition recommendations have emerged as a strategy for weight management, but evidence of their added value over standard advice remains inconclusive. This randomized controlled trial evaluated the effects of MyGeneMyDiet®, a genotype-informed lifestyle program, compared with standard recommendations on anthropometric, biochemical, and dietary outcomes in Filipino adults with overweight and obesity over 12 months. In this randomized controlled trial, participants received either MyGeneMyDiet® or standard recommendation (control). Both groups underwent regular nutrition counseling during the active phase (months 0–6) before transitioning to an inactive phase (free-living conditions, months 6–12). Primary outcomes included weight, BMI, waist circumference, and body fat percentage; secondary outcomes were dietary intake and biochemical markers. Analyses were conducted according to randomized group assignment. Primary analyses used available case-data at each timepoint, with paired t-tests for within-group comparisons and ANCOVA for between-group differences. Sensitivity analyses used Last Observation Carried Forward (LOCF) and Inverse Probability of Attrition Weighting (IPAW) to address loss-to-follow-up. Of the 136 screened, 52 initiated the intervention (MyGeneMyDiet®, n = 29; standard recommendation, n = 23), and 27 completed the 12-month follow-up (MyGeneMyDiet®, n = 15; standard recommendation, n = 12). Both groups lost weight over 12 months, with no evidence of meaningful between-group differences. During the 6-month active phase, baseline-adjusted analyses showed no significant between-group differences in weight (-0.36 kg [95
Implementing personalized dietary interventions has become important as emerging evidence indicates that dietary and lifestyle-dependent epigenetic modifications affect insulin resistance. An epigenome-wide association study (EWAS) was conducted on 1,684 non-diabetic adults aged 57–75 from the Framingham Offspring Study (FOS). Associations between dietary and lifestyle factors (assessed via food frequency questionnaire) and DNA methylation sites (DNA-MS) were analyzed, with adjustments for confounders (age, sex, lifestyle) and multiple testing. Significant epigenetic mediators were evaluated using causal mediation models. Validation was executed using the Genetics of Lipid-Lowering Drugs and Diet Network Study (n = 945). The EWAS identified 35 DNA-MS linked to HOMA-IR, with 13 DNA-MS showing significant associations with dietary factors in the FOS. Key DNA-MS including cg17901584 (DHCR24), influenced by brown rice (natural indirect effect: β ± SE, -0.02 ± 0.01, p = 0.0003), cg22761431 (EFNB3) by wheat germ (-0.01 ± 0.003, p = 0.001), and cg00574958 (CPT1A) associated with lactose (-0.001 ± 0.0003, p = 0.0001) intakes, all correlated with decreased HOMA-IR. Other DNA-MS, cg06808571 (KCNH2), cg06690548 (SLC7A11), and intergenic cg07504977, mediated increases in HOMA-IR linked to intakes of low-calorie cola (0.003 ± 0.001, p = 0.001), alcohol (0.01 ± 0.001, p = 9.0E-11), and palmitoleic acid (0.03 ± 0.01, p = 9.0E-05), respectively. In the GOLDN study, alcohol intake mediated by cg06690548 methylation in SLC7A11 was positively associated with HOMA-IR. Notably, the DHCR24 gene, crucial for cholesterol biosynthesis, was highlighted as a potential dietary target for reducing metabolic risk. The identification of specific DNA methylation sites, such as those in DHCR24 and EFNB3, provides supportive evidence for the mechanistic basis of known dietary effects on metabolic health. These findings not only reinforce the importance of diet in managing insulin resistance but also open avenues for personalized dietary interventions tailored to an individual’s epigenetic profile.
Polygenic predictors can enhance screening for metabolism-related traits such as body mass index (BMI) and type 2 diabetes (T2D). However, these predictors explain limited phenotypic variance and face implementation challenges in non-European populations. Dietary patterns are well-established metabolic risk factors that remain under-investigated in quantitative risk stratification models. We developed and evaluated risk stratification models combining polygenic predictors and data-driven dietary scores (DDS) for BMI and T2D in 14,346 Native Hawaiians from the Multiethnic Cohort (MEC-NH), a population with high prevalence of obesity and T2D. Using 5,374 participants with genetic data, we integrated publicly available large-scale GWAS summary statistics to develop cross-ancestry polygenic score (PGS) models using PRS-CSx. We developed DDS using machine learning algorithms on 520 dietary variables and evaluated model performance in held-out test sets. Trans-ancestry PGS achieved better prediction accuracy than single-ancestry models for both phenotypes (partial R² [SE] = 0.12 [0.04] vs. 0.03–0.09 for BMI; liability R² [SE] = 0.09 [0.04] vs. 0.01–0.07 for T2D). The best-performing DDS was based on a Random Forest model and substantially explained BMI variation (partial R² [SE] = 0.12 [0.01]), comparable to genetic prediction. Combined models integrating PGS and DDS significantly outperformed single-predictor models for BMI (adjusted R² = 0.29 vs. 0.21, P < 10⁻¹¹⁷). For T2D, combined models showed marginal but significant improvement over PGS alone. The BMI dietary score additionally associated with multiple chronic diseases, with effects partially mediated through inflammatory and lipid pathways. Trans-ancestry polygenic scores and data-driven dietary scores provide complementary information for metabolic trait prediction. Combined genetic-dietary models significantly outperform single-predictor approaches, with improvement being most pronounced for BMI. In Native Hawaiians, systematic integration of dietary information substantially improved BMI prediction, demonstrating the value of incorporating modifiable environmental factors alongside genetic information.
Gene expression in peripheral blood mononuclear cells (PBMCs) isolated from subjects before and after a 3-week walnut supplementation was examined for differentially expressed genes by RNA-seq. Significant gene expression changes were observed following walnut consumption with gene enrichment analysis showing significant overlap with genes previously associated with a robust memory B cell response following vaccination. An in-depth clustering analysis of the data revealed that a relatively large subpopulation of the subjects (11/19) showed a stronger and more uniform response to walnut consumption. This group of individuals showed an even more extensive overlap with genes associated with memory B cell production, with a significant overlap also observed for genes activated by an influenza vaccine adjuvant. The genes altered by walnut included numerous kinases and transcription factors, yet a deconvolution analysis did not reveal changes in the major PBMC cell types. Our findings show that a walnut supplementation can change gene expression in PBMCs in a manner consistent with a more responsive adaptive immune response without affecting the cellular composition of the blood.
Herbal compounds are widely recognized for their diverse biological activities, often targeting multiple pathways simultaneously. However, the hypoglycemic effect of liensinine and its underlying mechanisms remain poorly understood. This study aims to clarify how liensinine exerts its blood glucose-lowering effects, with a focus on its impact on pancreatic function and the gut microbiota. Thus, male C57BL/6 mice were randomly assigned to two dietary groups: a standard chow diet or a high-fat diet (HFD) for 4 weeks. Subsequently, type 2 diabetes mellitus (T2DM) was induced in HFD-fed mice using streptozotocin (STZ) injection, and the model was maintained for an additional four weeks. The mice were then further divided into four experimental groups: Control (standard chow), Negative Control (NC, chow-fed mice treated with liensinine at 60 mg/kg), Model (HFD + STZ-induced T2DM mice), and T2DM + Lien (T2DM mice treated with liensinine). The study employed Western blot, Immunofluorescence, and RT-qPCR techniques. Liensinine alleviated pancreatic injury and hepatic steatosis. It promoted islet cell proliferation, restored normal islet architecture, and balanced alpha- and beta-cell masses. Additionally, liensinine upregulated the expression of METTL3/14 (methyltransferases involved in RNA modification) and pancreatic duodenal homeobox 1 (PDX-1, a key regulator of pancreatic development). Meanwhile, liensinine reduced the abundance of Firmicutes, Lactobacillus, and Actinobacteriota, alongside increased levels of Bacteroides, Akkermansia, and norank_f_Muribaculaceae, concomitant with elevated short chain fatty acids (SCFAs) production in T2DM mice. In conclusion, these findings indicate that liensinine holds promise as a natural therapeutic agent, exerting beneficial effects on T2DM by ameliorating islet β-cell dysfunction and modulating gut microbiota.
Some studies indicate that psyllium supplementation may change lipid profile levels. This study assessed the impact of psyllium consumption on lipid profile (Low-Density Lipoprotein Cholesterol, Triglyceride, High-Density Lipoprotein Cholesterol, and cholesterol). We started searching articles using Scopus, Institute for Scientific Information Web of Science, and PubMed to identify eligible publications from March 15, 2022 to August 2, 2025. The effect of psyllium on lipid profiles in adults was evaluated through Randomized Controlled Trials. We calculated Weighted Mean Differences with 95
The intestinal epithelial barrier plays an essential role in protecting the body while allowing selective nutrient absorption. Natural bioactive compounds that strengthen this barrier contribute to gut health. However, the effects of pinoresinol, a dietary lignan known for its various bioactivities, on intestinal barrier function and underlying molecular mechanisms remain to be elucidated. Caco-2 monolayers were treated with pinoresinol, and barrier function was evaluated using fluorescein permeability and transepithelial electrical resistance (TEER) assays. The expression and localization of tight junction (TJ)-related proteins were analyzed by RT-PCR, western blotting, and immunofluorescence. The involvement of the CaMKKβ–AMPKα1 signaling pathway was also investigated. Pinoresinol improved barrier integrity by decreasing apparent permeability coefficient (Papp) and increasing TEER. It enhanced the expression and junctional localization of TJ-related proteins, including cingulin, occludin, and claudin-1. These effects were associated with activation of the CaMKKβ–AMPKα1 pathway, suggesting a mechanism through which pinoresinol reinforces the epithelial barrier function. This study identifies pinoresinol as a dietary bioactive compound that strengthens the intestinal barrier via activation of the CaMKKβ–AMPKα1 signaling axis. These findings provide mechanistic insight into its potential use as a functional ingredient for maintaining gut integrity and promoting overall intestinal health.
Cancer cachexia is a multifactorial syndrome characterized by systemic inflammation, progressive weight loss, muscle wasting, and metabolic alterations, which negatively affect quality of life, treatment response, and survival in cancer patients. Despite its prevalence and impact, effective treatments remain limited, in part due to the complex and poorly understood pathophysiology of the syndrome. Recent studies have revealed that gut microbiota alterations may contribute to the development and progression of cachexia through mechanisms involving immune activation, impaired gut barrier function, and disrupted metabolic signaling. This review explores the interplay between the altered gut microbiome and cancer cachexia, focusing on microbial metabolites such as short-chain fatty acids, gut barrier dysfunction and the impact of cancer therapies on microbial homeostasis. We evaluate emerging microbiota-targeted strategies, including traditional and next-generation probiotics and fecal microbiota transplantation, as novel therapeutic avenues. A deeper understanding of host–microbiome interactions may lead to the development of more effective, personalized interventions to improve cancer cachexia patient care.
