Search Results (3,195)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the greatest challenges for the modern public health system and serves as the foundation for the development of advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH), which may progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). MASLD and type 2 diabetes mellitus (T2DM) mutually exacerbate one another. MASLD increases the incidence of T2DM and the risk of complications in patients already affected. T2DM accelerates progression to MASH, which has become the second leading cause of liver transplantation and end-stage liver disease, and is associated with hepatic decompensation, cirrhosis, HCC, chronic kidney disease, and cardiovascular disease. MASLD and MASH are strongly linked to T2DM and obesity, pathogenesis including genetic polymorphisms, environmental factors, and multiple metabolic disturbances: insulin resistance (IR), gut dysbiosis, altered adipokine signaling, such as reduced adiponectin alongside increased pro-inflammatory cytokines. Inflammation plays a central role in the development of HCC in MASH, even in the absence of significant fibrosis. The Fibrosis-4 index (FIB-4) should be used as a first-line noninvasive tool to assess fibrosis risk. Additionally, ultrasound-based transient elastography (FibroScan) supports clinicians in assessing steatosis and fibrosis severity. Histologically, MASH is characterized by steatosis, lobular inflammatory changes, and ballooning degeneration of hepatocytes, with or without associated fibrosis. Accurately diagnosing and stratifying MASLD based on fibrosis risk is crucial to identify patients who may benefit from pharmacological treatment or can be managed only with lifestyle interventions. Patients should attain above 10% weight loss through lifestyle modifications. Resmetirom is recommended in F2/F3 fibrosis stages. For treating T2DM, glucagon-like peptide-1 receptor agonists and coagonists, sodium–glucose cotransporter-2 inhibitors, metformin (if glomerular filtration rate exceeds 30 ml/min), and insulin (in decompensated cirrhosis) are preferred. Clinical insights derived from trials are expected to optimize quality of life and long-term outcomes in patients with MASH. Full article

This study evaluated the alleviating effects of three heat-inactivated Enterococcus faecalis strains on growth suppression, oxidative stress, and gut microbiome dysbiosis in Macrobrachium rosenbergii-fed sesame meal-substituted fish meal diets. The trial comprised a control group (CT), low fish meal group (LF), and LF fed with three postbiotic-supplemented groups (LF+HK-448, LF+HK-798, LF+HK-804). Results demonstrated that compared with the CT group, the LF diet significantly decreased weight gain rate, specific growth rate, hepatopancreatic total nitric oxide synthase and inducible nitric oxide synthase, while increased feed conversion ratio, nitric oxide, and malondialdehyde contents. Among the postbiotics, LF+HK-804 group conferred the most pronounced compensatory growth and significantly improved oxidative stress and immune markers, as evidenced by elevated WGR, SGR, HSI, and flesh percentage, reduced MDA, and the down-regulation of Toll and Relish alongside the upregulation of peroxiredoxin-5. Intestinal microbiota analysis showed the group of LF+HK-804 improved microbial diversity and richness, specifically by increasing Firmicutes and decreasing Habeamium and Sphingomonas. Metabolomics identified 11 key differential metabolites related to amino acid, energy, and fatty acid metabolism. Correlation analysis further revealed that Gemmatimonadetes, WD2101_soil_group, and Sphingomonas were negatively correlated with phospholipids and positively correlated with glycoside and fatty acid metabolites. Moreover, immunometabolic correlation analysis segregated the metabolic response of microbiota into two distinct profiles: one potentiating a reactive oxygen/nitrogen species–antioxidant defense, and the other favoring a Dorsal/Relish-mediated transcriptional response. In conclusion, E. faecalis 804 can promote growth, alleviate oxidative damage, enhance immunity, and regulate intestinal microbiota and metabolic capacity in M. rosenbergii, showing great potential as a postbiotic. Full article

Colorectal cancer (CRC) cachexia is a multifactorial, treatment-limiting syndrome characterized by progressive loss of skeletal muscle with or without loss of fat mass, accompanied by systemic inflammation, anorexia, metabolic dysregulation, and impaired treatment tolerance. Despite decades of work, cachexia remains clinically underdiagnosed and therapeutically underserved, in part because canonical models treat tumor-derived factors and host inflammatory mediators as a largely ‘host-only’ network. In parallel, CRC is strongly linked to intestinal dysbiosis, barrier disruption, and microbial translocation. Extracellular vesicles (EVs)—host small EVs, tumor-derived EVs, and bacterial extracellular vesicles (including outer membrane vesicles)—may provide a mechanistically plausible, information-dense route by which these domains could be coupled. Here, we synthesize emerging evidence suggesting that cross-kingdom EV signaling may operate as a vesicular ecosystem spanning gut lumen, mucosa, circulation, and peripheral organs. We propose the “vesicular intersection layer” as a unifying framework for how heterogeneous EV cargos converge on shared host decoding hubs (e.g., pattern-recognition receptors and stress-response pathways) to potentially contribute to muscle catabolism. We critically evaluate what is known—and what remains unproven—about EV biogenesis, trafficking, and causal mechanisms in CRC cachexia, highlight methodological constraints in microbial EV isolation and attribution, and outline minimum evidentiary standards for cross-kingdom claims. Finally, we translate the framework into actionable hypotheses for EV-informed endotyping, biomarker development (including stool EV assays), and therapeutic strategies targeting shared signaling nodes (e.g., TLR4–p38) and endocrine mediators that are predominantly soluble but may be fractionally vesicle-associated (e.g., GDF15). By reframing CRC cachexia as an emergent property of tumor–host–microbiota vesicular communication, this review provides a roadmap for mechanistic studies and clinically tractable interventions. Full article

Background: Sepsis-induced organ dysfunction poses a significant clinical challenge with limited therapeutic options. This study investigated the therapeutic potential of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide in sepsis and its underlying mechanisms, focusing on modulation of the gut microbiota-derived metabolome. Methods: Public transcriptomic data analysis identified overlapping targets between liraglutide and sepsis-related genes. In a murine cecal ligation and puncture (CLP) model, liraglutide treatment was evaluated for its effects on survival, systemic inflammation, and organ injury. The gut microbiota composition and fecal metabolome were assessed via 16S rRNA sequencing and UPLC-MS. We also measured plasma GLP-1 in sepsis patients and examined the microbiota-dependency of liraglutide’s effects using antibiotic-depleted mice and fecal microbiota transplantation (FMT) from liraglutide-treated mice. Additionally, citrulline, a key identified metabolite, was functionally validated both in vitro and in a clinical cohort. Results: Liraglutide significantly improved survival, reduced pro-inflammatory cytokines, and alleviated lung, liver, and colon damage in septic mice. It partially restored sepsis-induced gut dysbiosis and modulating associated metabolites, including increasing citrulline. The survival benefit of liraglutide was abolished in microbiota-depleted mice, while FMT from liraglutide-treated mice conferred protection against sepsis, confirming the gut microbiota as a critical mediator. Furthermore, citrulline exhibited direct anti-inflammatory properties in cellular assays, and its plasma levels were negatively correlated with sepsis biomarkers (PCT and CRP) in patients. Conclusions: Taken together, our findings indicate that liraglutide mitigates sepsis by modulating the gut microbiota and regulating associated metabolic pathways. Citrulline may represent a potential microbial mediator or exploratory biomarker within this axis, warranting further mechanistic investigation. Full article

Background: Post-traumatic stress disorder (PTSD) and trauma-related disorders are increasingly recognized as complex conditions involving not only psychological and neurobiological factors but also systemic physiological alterations. Among these, growing evidence points to the crucial role of the gut–brain axis in modulating stress responses, emotional regulation, and neuroinflammation. Objective: This narrative review aims to synthesize the emerging literature on the interactions between the gut microbiota and the central nervous system in PTSD and trauma-related disorders, highlighting potential mechanisms and therapeutic implications. Methods: A comprehensive search of the literature was conducted across PubMed and Scopus and Web of Science as primary bibliographic databases, focusing on clinical, preclinical, and translational studies published in the last two decades. Emphasis was placed on studies exploring the microbiota’s influence on neuroendocrine and immune pathways relevant to trauma, as well as intervention studies targeting the gut–brain axis. Results: Evidence suggests that dysbiosis and gut permeability alterations are associated with PTSD symptomatology, possibly via mechanisms involving hypothalamic–pituitary–adrenal (HPA) axis dysregulation, neuroinflammation, vagal signaling, and altered neurotransmitter production. Preclinical models support a bidirectional relationship between early-life stress, trauma, and gut microbiota alterations. Furthermore, preliminary clinical data indicate that interventions such as probiotics, diet modulation, and psychobiotics may exert beneficial effects on trauma-related psychopathology. Conclusions: The gut–brain axis represents a promising framework for understanding the pathophysiology of PTSD and related conditions. Although research is still in its early stages, targeting gut microbiota may offer novel preventive and therapeutic strategies. Further longitudinal and mechanistic studies are needed to validate these findings and guide clinical translation. Full article

Background: Glaucoma is a neurodegenerative disease and the second leading cause of irreversible blindness in developed countries. It is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve axons, leading to permanent vision impairment. Although elevated intraocular pressure (IOP) is the main recognized risk factor, recent evidence suggests that ocular and gut microbiota may play a significant role in the onset and progression of glaucoma. Objectives: This study aimed to characterize ocular and gut microbiota alterations in patients with different types of glaucoma. Methods: Five searches were conducted between June and September 2025 using selected keywords. A total of 121 articles were identified, of which 14 met the inclusion criteria following the PRISMA 2020 guidelines. Results: Findings indicate a Mendelian genetic predisposition influencing microbiota composition associated with glaucoma development. Patients treated with benzalkonium chloride (BAK) showed increased Gram-negative and Alphaproteobacteria on the ocular surface, along with enhanced lipopolysaccharide synthesis. Compared with controls, glaucoma patients exhibited reduced Corynebacterium mastiditis and Actinobacteria and increased Firmicutes, Proteobacteria, and Verrucomicrobiota. Dysbiosis was more pronounced in patients with concurrent dry eye disease, characterized by higher Gram-negative taxa and pro-inflammatory microbial activity. Conclusions: Significant differences in ocular and gut microbiota were observed between glaucoma patients and controls, as well as among glaucoma subtypes such as pseudoexfoliation and primary open-angle glaucoma. Age-related dysbiosis and epigenetic factors appear to contribute to disease development. Microbiota profiling may offer new opportunities for improved prediction, management, and treatment of glaucoma. Full article

Major depressive disorder (MDD) ranks as a primary contributor to global ill health and disability, with treatments often proving insufficient. Recent study has increasingly found a strong correlation between gut microbiome diversity and mood-related behaviors, including MDD. Depression can alter gut microbiota (GM) composition, while intentional modulation of the GM may conversely influence depressive symptoms. This phenomenon arises from dynamic bidirectional interactions between the gut and brain, although the exact pathways are not yet fully elucidated. Proposed pathways include, but are not limited to, neural circuits, the endocrine system, immune responses, and metabolic regulation. Clinical data have also shown that regulating the GM through probiotics and prebiotics has the potential to alleviate depressive symptoms. This review summarizes contemporary research on the composition and modulatory functions of GM in MDD, and explores the predictive potential of GM for depression as well as the therapeutic prospects of probiotics, aiming to provide insights and directions for future research. Full article

Marine bioactive substances exhibit structural diversity and function-specific properties, attracting considerable interest in their potential applications in targeted nutritional delivery to the gut and microbiota regulation. These bioactive components, sourced from seaweed, marine crustaceans, and microorganisms, including polysaccharides, polyphenols, and lipids, demonstrate exceptional biocompatibility and specific recognition capabilities. They serve as an optimal carrier matrix and functional core for developing an efficient, precision-targeted intestinal nutrition delivery system. Research findings demonstrate that optimization via innovative delivery technologies, including nanoencapsulation and polymer microsphere encapsulation, enables marine bioactive substances to navigate various physiological barriers in the gastrointestinal tract effectively. This facilitates targeted, sustained release of nutritional components and enhances bioavailability. Simultaneously, these substances may relieve dysbiosis by modulating the composition of the gut microbiota and the quantity and activity of specific metabolic products, thereby reinforcing intestinal barrier integrity. This narrative review systematically examines the sources and functional attributes of marine bioactive compounds, emphasizing their application strategies in developing targeted delivery systems for the gut and their regulatory effects on gut microbiota. It concludes by delineating future research directions in this field, particularly in optimizing carrier functionalities and clarifying action mechanisms. Full article

Background/Objectives: The gut microbiota is increasingly recognized as a key determinant of human health, playing a vital role in metabolism, immunity, and disease susceptibility. Dysbiosis, or microbial imbalance, is associated with gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridioides difficile infection (CDI), as well as extraintestinal conditions, including obesity, cardiovascular disease, and neuropsychiatric disorders. This review aims to provide an updated overview of emerging therapeutic strategies to modulate the gut microbiota to restore eubiosis and improve health outcomes. Methods: A narrative review of recent literature was conducted, focusing on preclinical and clinical studies investigating microbiota-targeted therapies. The review primarily covers innovative interventional approaches, including fecal microbiota transplantation (FMT), bacterial consortium transplantation (BCT), bacteriophage therapy and outer membrane vesicles (OMVs). Results: Evidence supports the role of probiotics, prebiotics, and synbiotics in remodeling microbial communities and improving host health, although their effects may be strain- and context-dependent. FMT has demonstrated high efficacy in the treatment of recurrent Clostridium difficile infections and is being studied for IBD, IBS and extraintestinal diseases, following the recent Food and Drug Administration approval of the first commercial FMT products. BCT offers a standardized alternative to donor-derived material, with early clinical successes such as FDA-approved SER-109. Phage therapy and OMVs represent promising frontiers, offering targeted microbial modulation and interactions with the immune system, although clinical data remain limited. Conclusions: Emerging gut microbiota modulation strategies offer new perspectives for precision medicine and could transform the prevention and treatment of many diseases, but further studies are needed to ensure their safety, standardization, and clinical application. Full article

Metabolic endotoxemia has been proposed as a possible mechanism to explain the strong link between inflammation, obesity, and obesity-associated disorders. Gut dysbiosis is a hallmark of obesity, and diet has been reported to regulate both inflammation and disease risk by affecting the composition of gut microbiota and gut barrier function. In the condition of microbial imbalance and impaired intestinal mucosa, bacterial endotoxins, specifically lipopolysaccharides, translocate from the gut into the bloodstream, where they can sustain a prolonged, sterile, low-grade inflammation, raising the risk of several non-communicable diseases. Increasing evidence indicates that the risk and incidence of obesity and several obesity-associated disorders are sex-specific, although the underlying mechanisms are only just emerging. Notably, most of the factors influencing metabolic endotoxemia exhibit sexual dimorphism. This review aims to summarize the human studies investigating the role of metabolic endotoxemia in obesity and associated diseases, with a focus on those highlighting sex differences. We also discuss the clinical relevance of circulating endotoxins in metabolic derangements and their potential role as sex-related and modifiable risk factors to consider in future prevention strategies. Full article

Background/Objectives: This review is a concise summary of the current roles and indications for procalcitonin measurement in the management of patients with acute pancreatitis. Methods: The National Library of Medicine’s PubMed database for the period 1 January 2000 to 27 November 2025 was interrogated using the keywords “procalcitonin” and “acute pancreatitis”. Articles on gut dysbiosis in acute pancreatitis, procalcitonin and its role as a predictor of disease severity, a marker of pancreatic necrosis and a guide to antibiotic therapy in acute pancreatitis were retrieved. Results: Persistently elevated procalcitonin levels are indicators of disease severity and necrosis in acute pancreatitis. In the setting of acute pancreatitis with raised inflammatory markers, a procalcitonin level >1 ng/mL has evidentiary proof for use as an indicator for starting antibiotic therapy. Conclusions: In current practice, in patients with acute pancreatitis and raised inflammatory markers but without positive microbiological cultures, a procalcitonin level >1 ng/mL can be used as an indicator for starting antibiotic therapy. Full article

Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa—including Fusobacterium nucleatum (F. nucleatum)—have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management. Full article

As a major metabolic abnormality following hyperglycemia, hypertension, and hyperlipidemia, hyperuricemia has emerged as a significant global public health issue. The pathological mechanisms of hyperuricemia are complex; it not only directly triggers gout but is also closely associated with various chronic diseases, such as cardiovascular disease, diabetes, and chronic kidney disease, posing a systemic threat to individual health. This article systematically reviews the epidemiological characteristics, pathophysiological mechanisms, clinical consequences, and related risk factors of hyperuricemia, and especially focuses on the research advances and mechanisms of comprehensive intervention strategies, including diet, exercise, pharmacotherapy, and lifestyle modifications. Dietary interventions primarily function by regulating the activity of enzymes and transporters related to uric acid metabolism, ameliorating gut microbiota dysbiosis, and alleviating inflammatory responses. Exercise interventions synergistically improve uric acid homeostasis through multiple mechanisms, including the regulation of purine metabolic enzyme activity and the improvements of body composition, insulin resistance, and oxidative stress. Pharmacotherapy, serving as a core measure for patients with moderate-to-severe conditions, directly lowers serum uric acid levels by inhibiting uric acid production or promoting excretion. Although various intervention modalities exhibit distinct effects in regulating uric acid production, promoting excretion, and improving the metabolic-inflammatory environment, challenges such as significant heterogeneity in individual response and uncertainty regarding long-term efficacy remain prevalent. Furthermore, given the increasing trend toward a younger onset of hyperuricemia, prevention and control strategies targeting children and adolescents require urgent reinforcement. Future efforts should focus on conducting multi-center, large-sample clinical studies with clear mechanisms and establishing individualized health management plans based on population characteristics, thereby promoting the precise prevention and treatment of hyperuricemia. Full article

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut–Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation of indoxyl sulfate, which is proposed to promote carcinogenesis via Aryl Hydrocarbon Receptor (AhR) and Akt signaling, ultimately upregulating c-Myc and EGFR. We propose a two-compartment model: while systemic indoxyl sulfate reflects the total gut indole pool (mainly from planktonic bacteria), adherent bacteria like Fusobacterium nucleatum may create high-concentration indole hotspots within the tumor microenvironment. Clinically, we advocate for protein-independent DNA methylation biomarkers (SEPT9, SDC2) to avoid renal confounding. Furthermore, we propose a novel diagnostic panel integrating serum indoxyl sulfate (systemic load) and urinary indoxyl sulfate (gut production) to guide therapy. Therapeutically, targeting upstream drivers (AhR/Akt) may bypass resistance to anti-EGFR therapies in KRAS-mutated tumors. We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC. Full article

Escherichia coli O157:H7 is a pathogenic bacterium that causes severe intestinal infections characterized by inflammation and disruption of the intestinal barrier. Probiotic lactic acid bacteria (LAB) from milk can support intestinal health and combat enteric pathogens; however, the potential of feline milk-derived LAB against E. coli O157:H7 infection remains unclear. In this study, Pediococcus acidilactici (P. acidilactici) M22, isolated from feline milk, was evaluated for probiotic activity in vitro and in vivo in a C57BL/6 mouse model of Escherichia coli O157:H7 infection. In vitro assays demonstrated that M22 significantly inhibited the adhesion of Escherichia coli O157:H7 to intestinal epithelial cells. For in vivo assessment, C57BL/6 mice were orally administered M22 prior to infection with E. coli O157:H7. Protective effects were evaluated by monitoring body weight loss, colon length, disease activity index (DAI), myeloperoxidase (MPO) activity, cytokine levels, tight junction protein expression, oxidative stress markers, and gut microbiota composition. M22-treated mice exhibited significantly less body weight loss and lower DAI scores than infected controls. M22 also prevented colon shortening, indicating reduced colonic damage. Probiotic treatment attenuated neutrophil infiltration and mucosal inflammation, as evidenced by decreased colonic MPO activity, reduced levels of pro-inflammatory cytokines, and elevated anti-inflammatory IL-10. Additionally, M22 preserved intestinal barrier function by upregulating tight junction proteins and mitigating infection-induced histopathological changes. M22 supplementation enhanced antioxidant defenses in colonic tissue (lower malondialdehyde, higher superoxide dismutase and glutathione), indicating reduced oxidative stress. Furthermore, gut microbiota analysis (16S rRNA sequencing) revealed that M22 counteracted infection-induced dysbiosis, restoring microbial diversity and a healthy composition (enrichment of beneficial commensals and suppression of harmful bacteria). By safeguarding intestinal integrity and homeostasis, M22 emerges as a promising next-generation probiotic for improving intestinal health in companion animals. Full article