Search Results (512)

Environmental toxins can impair gut microbiota and increase intestinal permeability, contributing to various health problems. While many such toxins are known to disrupt tight junctions and compromise barrier function, research specifically examining carbon tetrachloride (CCl₄) as a trigger of intestinal epithelial barrier dysfunction remains limited. In this study, 54 young Western albino male rats, weighing 180–200 g, were randomly assigned to nine experimental groups, each comprising six rats. Group 1 received 1 mL of oral saline and served as a control. Groups 2 and 3 received 0.2 g/kg body weight probiotic and prebiotic, respectively, for four weeks. CCl₄ (1 mL/kg, i.p.) was administered either at the beginning of day 1 (damage induction; Group 4) or at the end of day 28 (protection assessment; Group 7). Intervention groups received probiotics and prebiotics for 4 weeks after (therapeutic) CCl₄ exposure on day 1 in Groups 5 and 6, respectively. Groups 8 and 9 received probiotics and prebiotics for 4 weeks before CCl₄ exposure on day 28, respectively. Quantification of gut bacterial populations, serum levels of Occludin and Zonulin, as biomarkers of intestinal permeability, and histopathological analysis of intestinal tissue were conducted. CCl₄ induces significant intestinal epithelial barrier dysfunction with marked histopathological alterations. Probiotic treatment was more effective than prebiotics at normalizing serum Zonulin and Occludin levels in CCl₄-induced intestinal damage. Probiotics restore microbial balance by suppressing the overgrowth of pathogenic organisms, while prebiotics confer partial protection. CCl₄-induced gut barrier disruption is restored through probiotic supplements by restoring gut microbial balance and normalizing tight junction-associated biomarkers. Full article

Inflammatory bowel disease (IBD) is characterized by chronic and intermittent symptoms, exerting a profound impact on overall health. Although drug therapy and biological agents are primary treatment approaches for IBD, the side effects can affect human health. Thus, it is an urgent need to explore new approaches to counteract the harm caused by IBD. Owing to their natural origin and excellent biosafety, casein peptides are a promising candidate treatment for IBD. This review systematically outlines the structural basis of the intestinal barrier and elucidates the pivotal role of barrier dysfunction in IBD pathogenesis. We further elaborate on the multi-faceted therapeutic mechanisms of casein peptides in IBD, including intestinal barrier repair, immune homeostasis modulation, inflammatory response suppression, and other such pathways. Moreover, we analyze the key challenges of intestinal-barrier-targeted casein peptide therapies in current research and translational practice, and propose future perspectives for overcoming these limitations, thus providing a reference for potential new preventive and therapeutic approaches to IBD. Full article

Microplastics (MPs) are increasingly recognized as a global environmental threat. Emerging evidence suggests they may have metabolic consequences. In this review, we synthesize current findings from animal and in vitro studies to propose a mechanistic framework linking MP exposure to type 2 diabetes mellitus (T2DM). This framework is uniquely centered on the gut–liver axis and macrophage-centric immune networks. We systematically delineate evidence suggesting that MPs can compromise intestinal barrier integrity, instigate gut dysbiosis, and promote pro-inflammatory M1 polarization of macrophages in experimental models. This immune activation is proposed to subsequently amplify hepatic inflammation, potentially contributing to systemic insulin resistance (IR) and pancreatic β-cell dysfunction. We emphasize that while this pathway is biologically plausible, direct causal evidence in humans remains limited and is a critical knowledge gap. Integrating multi-level evidence from animal models and in vitro systems, we delve into the trans-organ immunometabolic effects of MPs within adipose tissue, pancreas, and skeletal muscle, establishing their role as a novel class of “metabolic disruptors.” Critically, we assess the key controversies and knowledge gaps pertaining to dose–response relationships, particle-specific toxicity (size, polymer type, and additives), the effects of complex environmental mixtures, and the urgent need for robust human validation. We advocate for future research priorities, including multi-omics integration, advanced organ-on-a-chip platforms, prospective cohort studies, and targeted intervention strategies, to propel this field from mechanistic exploration toward clinical and public health relevance. Finally, this synthesis underscores that mitigating the production and environmental release of MPs, alongside developing strategies to impede their bioavailability and accumulation, represents a crucial public health imperative for the prevention of environment-related metabolic diseases. Full article

Inflammatory bowel diseases (IBDs) and metabolic disorders are increasingly recognized as interconnected conditions that frequently coexist and influence each other’s clinical course. Accumulating evidence indicates that patients with IBD face a substantial burden of obesity, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease, osteoporosis, and type 2 diabetes. These associations appear to be driven by shared and interacting mechanisms, including intestinal barrier disruption, gut microbiota dysbiosis, chronic systemic inflammation, and adipose tissue-mediated immunometabolic pathways. Metabolic comorbidities may worsen IBD activity, reduce response to therapy, increase complications, and contribute to higher health care utilization. Conversely, intestinal inflammation and commonly used treatments, particularly corticosteroids, can adversely affect glucose metabolism, lipid metabolism, body composition and bone homeostasis. Advanced therapies have demonstrated variable metabolic effects, some of which may be beneficial through suppression of systemic inflammation. Recognition of these bidirectional interactions highlights the importance of routine metabolic screening and integrated, multidisciplinary management. Lifestyle interventions, nutritional optimization and individualized therapeutic strategies represent central parts of comprehensive management. Full article

Global climate change has increased the frequency and intensity of heat waves, posing a significant threat to livestock production. During heat exposure, the disruption of intestinal barrier integrity is a pivotal event in the pathogenesis of heat stress-induced intestinal injury. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are key consequences of heat stress at the cellular level. However, direct causal evidence linking ER stress to mitochondrial dysfunction in heat-stressed enterocytes remains limited. To investigate this, we used an integrated transcriptomic, metabolomic, and functional validation strategy to assess mitochondrial bioenergetics and cellular ultrastructure in porcine intestinal epithelial (IPEC-J2) cells under acute heat stress. Transcriptomic analysis revealed extensive reprogramming, highlighting the significant enrichment of pathways related to protein processing in the endoplasmic reticulum, apoptosis, and MAPK signaling. Untargeted metabolomics identified significant perturbations in amino acid and energy metabolism, as well as altered bile acid profiles. Functional assessments confirmed that heat stress severely impaired mitochondrial bioenergetics, as evidenced by reduced maximal respiration and ATP production, and induced ultrastructural damage to mitochondria. The pharmacological inhibition of ER stress by 4-phenylbutyric acid (4-PBA) significantly attenuated the mitochondrial bioenergetic impairment and ultrastructural damage, whereas ER stress induction recapitulated these defects. We demonstrate that heat stress induces profound transcriptional and metabolic remodeling characterized by ER stress activation, which critically mediates subsequent mitochondrial bioenergetic dysfunction and ultrastructural damage. Our findings suggest that targeting ER stress may represent a promising therapeutic strategy to ameliorate enterocyte mitochondrial dysfunction and mitigate heat stress-induced intestinal injury in livestock. Full article

High-fat diets (HFDs) are major environmental factors influencing metabolic homeostasis, immune regulation, and brain function, largely through their effects on gut microbiota and intestinal barrier integrity. Disruption of the microbiome–brain–gut axis has been increasingly implicated in systemic and neuroinflammatory processes; however, the molecular mediators that integrate dietary lipid signals with microbial and host responses remain incompletely defined. This review synthesizes the current evidence on the role of fatty acid-binding protein 4 (FABP4) as an integrative node linking HFD-induced gut dysbiosis to systemic and central inflammatory signaling. We critically evaluated experimental and translational studies addressing HFD-driven alterations in gut microbiota composition, intestinal barrier function, and inflammatory pathways, with particular emphasis on FABP4-mediated mechanisms across epithelial, immune, and neural compartments. The available data indicate that FABP4 responds to dietary and microbiome-derived cues and contributes to coordinated metabolic and inflammatory responses, affecting both peripheral tissues and the central nervous system. These findings support a model in which FABP4 participates in diet-driven feedback loops that amplify gut barrier dysfunction, immune activation, and neuroinflammation. In conclusion, FABP4 emerges as a central molecular mediator within the microbiome–brain–gut axis under HFD conditions, highlighting its potential relevance in understanding the pathophysiology of metabolic and neuroinflammatory disorders and guiding future integrative research strategies. Full article

Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, which involves oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) in a mouse model of colitis induced by dextran sulfate sodium (DSS). Based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology, 25 major bioactive components were identified. Following the induction of colitis with 3.5% DSS in C57BL/6J mice, the animals were treated with the GSNS (40, 80, or 160 mg/kg/day) or 5-Amino Salicylic Acid (5-ASA). The therapeutic efficacy was assessed via disease activity, histopathological staining, cytokines and oxidative stress analysis, and a barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of the GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and was associated with beneficial alterations in the gut microbiota, as evidenced by increased Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that the GSNS exerts a multi-target effect against colitis by synergistically enhancing antioxidant defense, repairing the intestinal barrier, and modulating microbial ecology, supporting its potential as a promising natural compound-based candidate for DSS-induced colitis treatment. Full article

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder linked to gut microbiota dysbiosis and impaired inter-organ metabolic signalling. This study investigated the combined effects of the probiotic Lactiplantibacillus plantarum TJA7 and Mulberry Leaf extract (Morus alba) on cellular processes relevant to T2DM-related metabolic dysfunction. An advanced in vitro gut–pancreas–liver axis model, using Caco-2, EndoC-βH5, and HepG2 cells, was employed under hyperglycemic and oxidative stress conditions. The combined treatment consistently outperformed the individual components by improving intestinal barrier integrity, as indicated by increased transepithelial electrical resistance (TEER), and by enhancing butyrate translocation across the intestinal layer. Metabolites derived from the combination attenuated pancreatic β-cell dysfunction, reducing reactive oxygen species (ROS) levels and increased insulin secretion (1.7-fold compared with Mulberry Leaf extract alone). At the hepatic level, co-administration modulated key glucose metabolism pathways, including Insulin Receptor Substrate 1 (IRS1), Protein Kinase B (AKT), AMP-Activated Protein Kinase (AMPK), and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1α), suggesting improved cellular glucose handling. Collectively, these findings support a positive dose-specific interaction under the tested conditions and provide a biologically plausible, hypothesis-generating framework for probiotic–phytochemical cooperation along the gut–pancreas–liver axis. Further in vivo and clinical studies are required to establish causality and translational relevance. Full article

The gut microbiota’s (GM) regulation of inflammation and oxidative stress is supported by existing evidence, and its dysregulation relates to brain disease. Indeed, probiotics and prebiotics have been shown to improve cognitive function. This is associated with a stronger gut and blood–brain barrier and less gut inflammation. Oligofructose-enriched inulin alters the GM, reduces body fat, and lowers interleukin-6 (IL-6) in obese patients. Moreover, by increasing glutathione (GSH), the ketogenic diet (KD) prevents seizures and also benefits the intestinal short-chain fatty acid (SCFA) profile. Given the evidence on managing epileptic conditions, the aim of this review is to assess how changing the gut microbiota (GM) can be a therapeutic method for preventing neurodegenerative dysfunctions associated with epileptic seizure onset and progression, with a focus on innovative supplement strategies, including endogenous and exogenous antioxidants, nutrition, and new phyto-therapies. Indeed, though drugs are the main treatment for epilepsy, the KD and other supplements are increasingly being considered. These compounds affect neuronal excitability, neurotransmitter release, and neuroinflammation, thus providing an anticonvulsant effect. Specifically, the KD prevents seizures by increasing GSH levels, which represents a crucial endogenous antioxidant that plays a key role in counteracting neuroinflammation and gut microbiota dysfunction. Furthermore, due to their antioxidant and anti-inflammatory properties, plant extract derivatives may be new agents that could reduce neuroinflammation in seizures, affecting the gut–brain axis (GBA) through the intestinal microbiota. In conclusion, data suggest that further clinical studies are needed to explore how the GM impacts epilepsy, and how specific nutraceuticals might offer probiotic benefits. Thus, a combined effect of nutraceuticals and functional food might be appealing, potentially resulting in a more beneficial therapeutic outcome. Full article

Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share symptoms such as abdominal pain, bloating, and altered bowel habits. Both are linked to dysbiosis and gut–brain axis dysfunction. IBS is a multifactorial disorder characterized by abnormal motility, visceral hypersensitivity, low-grade inflammation, and alterations in the microbiota. In contrast, SIBO is defined by excessive bacterial colonization of the small intestine that can mimic or worsen IBS symptoms. Gut microbes and their metabolites influence motility, immune activation, barrier integrity, and gas production; methanogen overgrowth is associated with constipation-predominant presentations, while hydrogen- and hydrogen sulfide-related pathways may contribute to diarrhea and bloating. Because recurrent or empiric antibiotic use is common—particularly in suspected SIBO—yet carries risks of resistance, microbiome disruption, and relapse, there is a strong rationale to prioritize effective non-antibiotic strategies. Accordingly, this review synthesizes current evidence on IBS/SIBO pathophysiology and microbiota interactions. It evaluates non-pharmacological interventions including dietary approaches, probiotics/prebiotics, herbal therapies, and mind–body treatments (e.g., cognitive behavioral therapy and gut-directed hypnotherapy). We emphasize an integrative framework that supports symptom control and quality of life while helping reduce unnecessary antibiotic exposure. Full article

Diabetes mellitus is one of the most common health problems worldwide; however, increased blood glucose alone cannot adequately explain its pathophysiology. Although high blood glucose is a defining feature, evidence increasingly proves that diabetes arises from systemic disturbances involving the gut microbiome, immune system, and metabolic control. From this perspective, diabetes can be viewed as a systemic condition shaped by the dynamic interactions between the gut microbiome, the immune system, and metabolic pathways. Alterations in gut microbiome composition and function can influence nutrient metabolism, microbial metabolite production, bile acid signaling, and intestinal barrier integrity. Any damage of the gut barrier allows movement of microbiome-derived molecules that activate innate immune pathways and provoke chronic low-grade inflammation. This inflammatory state interferes with insulin signaling, contributes to immune maladaptation, and exacerbates metabolic dysfunction. Over time, these processes contribute to the advance of multisystem complications, including cardiovascular disease, diabetic nephropathy, neuropathy with cognitive impairment, delayed wound healing, and increased susceptibility to infection. The review also integrates environmental and public health factors, demonstrating how diet, antibiotic exposure, circadian disruption, and social conditions shape the microbiome, immune function, metabolic regulation, and disease risk across the life course. By bringing together clinical, experimental, and population-based evidence, this review illustrates the limitations of care models that concentrate only on glucose. It also points out how integrated approaches targeting the microbiome, immune system, and metabolic pathways can improve diabetes prevention, management, and guide future research. Full article

Background and Objectives: Cardiometabolic disease, a term encompassing metabolic syndrome (MS) and cardiovascular disease (CVD), represents a major and growing global health burden driven by interconnected metabolic and cardiovascular dysfunction. Emerging evidence suggests that the gut microbiota plays a central role in modulating metabolic, inflammatory, and cardiovascular (CV) pathways, giving rise to the concept of the heart–gut axis. However, human evidence integrating microbiome-mediated mechanisms across the cardiometabolic spectrum remains incompletely synthesized. This focused systematic review aimed to synthesize the current human evidence on microbiome-mediated mechanisms linking metabolic syndrome (MS) and related metabolic phenotypes with cardiovascular risk (CVR) and subclinical cardiovascular (CV) outcomes within the conceptual framework of the heart–gut axis. Materials and Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library in accordance with PRISMA 2020 guidelines. Human observational and interventional studies evaluating gut microbiota composition, function, or microbiota-derived metabolites in relation to cardiometabolic, and CV outcomes were included. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools, and findings were synthesized narratively. Results: Ten human studies published between 2016 and 2025 met the inclusion criteria. Across these studies, gut dysbiosis was consistently associated with adverse cardiometabolic risk profiles and subclinical CV outcomes, including insulin resistance, systemic inflammation, subclinical atherosclerosis, and CV prognosis in high-risk populations. Microbiota-derived metabolites, particularly trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), as well as emerging metabolites such as phenylacetylglutamine (PAGln) and imidazole propionate (ImP), were identified as key mediators linking metabolic syndrome and related metabolic disturbances with CVR and subclinical cardiovascular disease (CVD). Markers of intestinal barrier dysfunction and endotoxemia further supported the role of chronic low-grade inflammation within the heart–gut axis. Conclusions: Current human evidence supports the heart–gut axis as a biologically plausible and clinically relevant contributor to cardiometabolic disease. Gut microbiota-derived metabolites, intestinal barrier dysfunction, and systemic inflammation represent interconnected pathways linking MS with CVR. Advancing our understanding of these mechanisms may inform the development of microbiome-targeted strategies to complement established approaches for cardiometabolic and CV prevention. Full article

Background/Objectives: This study investigated the systemic metabolic effects of two probiotic strains, Lacticaseibacillus paracasei MG5012 and Bifidobacterium animalis subsp. lactis MG741, on metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity-related muscle dysfunction in high-fat-diet (HFD)-induced obese mice. Methods: Obesity was induced in C57BL/6 mice via high-fat diet (HFD) feeding for 6 weeks. Subsequently, the mice were orally administered MG5012 or MG741 for 8 weeks. We assessed systemic metabolic parameters, including body weight, adiposity, and serum biomarkers. Additionally, histological and molecular analyses were performed to evaluate hepatic steatosis, intestinal barrier integrity, and muscle oxidative status. Results: Both strains significantly attenuated body weight gain and adiposity, reduced serum liver injury markers (γ-GTP, ALT, AST), and improved systemic metabolic parameters by restoring serum GLP-1 levels and reducing hyperinsulinemia. Crucially, MG5012 and MG741 strengthened intestinal barrier integrity by upregulating the tight junction proteins Occludin and Claudin-1. In the liver, histological analyses revealed reductions in hepatic steatosis and triglyceride content, accompanied by the downregulation of lipogenic genes (SREBP-1c, FAS). Furthermore, the probiotics preserved skeletal muscle integrity; while muscle weight remained unchanged, the strains increased muscle fiber cross-sectional area (CSA) and reduced serum markers of muscle damage (CPK, LDH). This protective effect was associated with significantly enhanced expression of antioxidant enzymes (SOD, CAT, GPx) in muscle tissue. Conclusions: These findings suggest that MG5012 and MG741 confer systemic metabolic benefits through the modulation of the gut–liver–muscle axis and may serve as promising functional food ingredients for the management of MASLD and obesity-associated muscle atrophy. Full article

Introduction: Intensive chemotherapy protocols and hematopoietic stem cell transplantation (HSCT) in children with cancer frequently lead to severe complications, such as mucositis and immune dysfunction. A growing body of evidence indicates that these complications are closely associated with the patient’s nutritional status and the composition of the gut microbiome, which becomes profoundly destabilized as a result of cytotoxic therapy and antibiotic use. Background: The aim of this review is to critically evaluate the current state of knowledge on the interplay between gut dysbiosis, metabolomic profiles—with particular emphasis on short-chain fatty acids (SCFAs)—and treatment-related toxicity in pediatric patients, as well as to delineate pathways toward personalized nutritional therapy. Methods: A narrative review was conducted, including clinical and preclinical studies published between January 2015 and October 2025. PubMed/MEDLINE, Embase, Cochrane Library, and other databases were searched, focusing on changes in microbiome composition, correlations between gut-derived metabolites and the severity of complications (sepsis, graft-versus-host disease [GvHD], mucositis), and the effects of targeted nutritional interventions (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation [FMT]) on microbiome modulation during anticancer therapy. Results: The analysis demonstrates that pediatric oncologic treatment leads to a marked reduction in microbial diversity, including the loss of protective Clostridiales taxa (e.g., Faecalibacterium), accompanied by an overgrowth of Proteobacteria pathobionts. Metabolomic profiling indicates that low SCFA levels (e.g., butyrate < 20–50 µmol/g) are a strong predictor of severe mucositis, prolonged neutropenia, and an increased risk of sepsis. Interventions aimed at restoring eubiosis and enhancing SCFA production show potential in strengthening the intestinal barrier, modulating immune responses, and enabling maintenance of the planned relative dose intensity (RDI) of chemotherapy by reducing treatment-related toxicity. Conclusions: Gut microbiome profiling and fecal metabolomics represent promising prognostic tools in pediatric oncology. There is an urgent need for further research employing “omics”-based approaches to develop precise, individually tailored nutritional protocols. Such strategies, including postbiotics and FMT, may minimize treatment-related adverse effects and improve long-term clinical outcomes in pediatric patients. Full article

Post-cholecystectomy non-alcoholic fatty liver disease (NAFLD), now encompassed within metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly linked to persistent disruption of bile acid kinetics and gut–liver axis signaling after gallbladder removal. Continuous bile delivery to the intestine reshapes the bile acid pool, perturbs FXR–FGF19/TGR5 pathways, remodels gut microbiota, and compromises epithelial barrier integrity, collectively promoting portal endotoxemia, chronic hepatic inflammation, and fibrogenic remodeling. Hydrogel-based biomaterials offer a mechanistically aligned therapeutic platform for this setting because they enable localized, sustained, and stimuli-responsive interventions at intestinal or hepatic sites. Functional hydrogels can sequester excess bile acids, protect and deliver probiotics/prebiotics/postbiotics, reinforce mucosal barrier function, and provide controlled release of anti-inflammatory or antifibrotic agents with reduced systemic exposure. In this review, we map emerging hydrogel strategies relevant to post-cholecystectomy NAFLD across four pathogenic nodes, bile acid dysregulation, dysbiosis, inflammation, and fibrosis, and highlight design principles (polymer chemistry, charge/hydrophobicity balance, mucoadhesion, and pH/redox/enzyme responsiveness) that enable targeted modulation of the gut–liver axis. Finally, we identify key translational gaps, including the lack of post-cholecystectomy-specific experimental models and standardized outcome measures integrating bile acid profiling, microbiome readouts, and hepatic histology. Hydrogel technologies represent a promising route toward localized and multimodal therapy in metabolic liver disease, warranting focused preclinical validation and clinical development. Full article