Search Results (1,425)

With colorectal cancer (CRC) accounting for over 1.9 million new cases and 930,000 deaths globally in 2020, there is a critical need for innovative indicators to forecast disease advancement and therapeutic outcomes. The gut microbiome has emerged as a fertile area for discovering such diagnostic and prognostic signals. This narrative review collected current evidence on intestinal microorganisms and their metabolic products as candidate markers for CRC control. Intestinal communities influence malignancy through diverse mechanisms, including metabolic shifts, immune modulation, inflammation, proliferation/apoptosis regulation, genotoxicity, and mucosal barrier disruption. Pathogenic species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis, facilitate tumorigenesis via FadA-mediated signaling and Th17/IL-17 responses. In contrast, beneficial taxa like Faecalibacterium prausnitzii and Akkermansia muciniphila provide protective effects through short chain fatty acid production. Macrophage phenotype physiological equilibrium is altered and inflammatory status fluctuates under the former. Metabolically, hydrogen sulfide damages mitochondrial DNA and secondary bile acids stimulate cellular proliferation. While 16S rRNA sequencing and shotgun metagenomics are established detection strategies, innovative platforms like organoids and gene arrays remain in the exploratory stage. Clinical data indicates that F. nucleatum aligns with advanced tumor stage, and its combined detection with colibactin-producing E. coli achieves high sensitivity for early-stage screening. Additionally, A. muciniphila levels can anticipate the efficacy of PD-1 blockade immunotherapy. Microbiota-derived tools represent a transformative direction in oncology. Future research must focus on standardizing protocols and validating multi-marker panels to enhance clinical translation. Full article

Background: To examine the antioxidant and anti-inflammatory effects of sitagliptin in restoring the intestinal mucosal barrier in rats with colitis induced by dextran sulfate sodium (DSS). Methods: Male Sprague-Dawley rats were administered 5% DSS in their drinking water to induce colitis. Sitagliptin was administered intragastrically at a dose of 15 mg/kg/day for a duration of eight days. Changes in the colon tissue were histologically examined, and the disease activity index (DAI) score was measured. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were evaluated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, tight junction proteins occludin and ZO-1 was assessed. Levels of SGOT, SGPT, and serum iron were also measured. Results: Sitagliptin diminished DAI and histological index scores, as well as MDA levels, while augmenting SOD, GPx, and catalase levels over an eight-day period. Based on proinflammatory cytokines, sitagliptin reduced colon inflammation. Compared to the untreated DSS group, sitagliptin increased serum iron and lowered SGOT and SGPT. Conclusions: The present results indicate that administering sitagliptin orally for a week could aid in the recovery from DSS-induced colitis by reducing oxidative stress and pro-inflammatory cytokines. Additional studies are required to make this applicable for patients suffering from colitis. Full article

Irritable bowel syndrome (IBS) is a multifactorial functional intestinal disorder whose pathogenesis involves intestinal microbiota imbalance, mucosal barrier impairment, immune–inflammatory responses, and dysregulation of the gut–brain axis. Lactobacillus reuteri has been shown to modulate the gut microbiota, produce antimicrobial metabolites, strengthen the intestinal mucosal barrier, suppress inflammatory responses, and participate in gut–brain axis regulation, thereby potentially contributing to the maintenance of intestinal homeostasis and the alleviation of IBS-related symptoms. These findings indicate that L. reuteri holds potential therapeutic value in the prevention and treatment of IBS. However, the majority of supporting evidence derives from animal experiments, in vitro studies, or indirect sources, and its precise mechanisms of action and clinical efficacy warrant further investigation. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory condition resulting from complex interactions between the immune system, genetic predisposition, and the gut microbiota. In this context, Escherichia coli (E. coli) plays a dual role in the human gut, ranging from harmless commensal strains to pathobionts capable of promoting intestinal inflammation. A growing body of evidence suggests that specific E. coli pathotypes, such as adherent-invasive E. coli (AIEC) and diffusely adherent E. coli (DAEC), contribute to the development and progression of IBD. This narrative review critically examines the microbiological, immunological, and clinical evidence supporting the role of E. coli in IBD, with particular emphasis on mechanisms of mucosal colonization, host–microbe interactions, and persistence within the inflamed intestinal environment. Furthermore, the lack of a standardized operational definition and the limited reproducibility of the AIEC phenotype are addressed, as well as uncertainty about the role played by E. coli as a primary initiator of the disease or as an opportunistic amplifier of intestinal inflammation, and the varying strength of evidence supporting associations with Crohn’s disease versus ulcerative colitis. Diagnostic implications, antimicrobial resistance, and therapeutic aspects are addressed as downstream and context-dependent consequences of E. coli–host interactions, with relevance for disease management and therapeutic response in patients with established IBD. By integrating data from experimental models, clinical studies, and translational research, the review identifies areas of consensus, ongoing controversy, and major knowledge gaps in IBD pathophysiology and clinical practice. Full article

The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising application prospects in the prevention and treatment of MASLD. However, basic research on their toxicity still lags behind, and issues related to safety and clinical translation urgently need attention. This article systematically reviews the research progress on how flavonoids, triterpenoids, alkaloids, and polysaccharides improve hepatic steatosis, inflammatory responses, and metabolic disorders from a toxicological perspective by reshaping the intestinal microbiota, repairing the intestinal mucosal barrier, regulating short-chain fatty acid and bile acid metabolism, and synergistically acting on signaling pathways such as TLR4/NF-kB, FXR, TGR5, SIRT1, and the NLRP3 inflammasome. Furthermore, by combining methods such as 16S rRNA sequencing, metagenomics, metabolomics, and multi-omics integration, the article analyzes their application value and limitations in toxicological mechanism research, and discusses the translational bottlenecks faced by Chinese herbal monomers in pharmacokinetics, bioavailability, quality standardization, targeted delivery, and toxicological safety. Existing evidence indicates that Chinese herbal monomers have a three-in-one intervention advantage of microecological remodeling-metabolic regulation-inflammation inhibition, but their long-term medication safety, toxic target organs, dose-effect/toxicity relationships, and potential drug interactions still need further clarification. This article aims to provide a systematic reference for the safety evaluation and clinical translational research of Chinese herbal monomers in the prevention and treatment of MASLD. Full article

This study systematically evaluated the modulatory effects of Brassica rapa L. polysaccharides (BRP) on intestinal mucosal injury in a CTX-induced mouse model. The results showed that high-dose BRP (HBRP) significantly alleviated oxidative damage, with CAT activity increased by approximately 2-fold, SOD increased by 1.3-fold, GSH-Px increased by 70%, and MDA levels decreased by 65%. Meanwhile, liver injury was improved, as ALT and AST decreased by 35% and 55%, respectively. CTX markedly suppressed immune function, while BRP intervention significantly restored cytokine levels, with IL-1β increased by up to 2.5-fold, TNF-α by 1.3-fold, and IL-4 by 2.1-fold. In addition, BRP significantly modulated gut microbiota composition. The number of unique ASVs decreased from 316 in the normal control (NC) group to 63 in the model control (MC) group and recovered to 140 in the HBRP group. At the phylum level, Bacillota increased from 55% to 97% (MC) and decreased to 65% after BRP intervention, while Bacteroidota recovered to 25%. At the genus level, Candidatus_Arthromitus decreased from 40% to nearly 0%, whereas beneficial bacteria such as Ligilactobacillus and norank_f__Muribaculaceae were restored. Overall, BRP effectively alleviates CTX-induced intestinal injury in a dose-dependent manner through antioxidant, immunomodulatory, and gut microbiota–regulating mechanisms. Full article

This study aimed to evaluate the protective effects of soluble dietary fiber (SDF) derived from Polygonatum cyrtonema Hua residues on cyclophosphamide (CTX)-induced intestinal injury in mice. A total of 60 C57BL/6 mice (6–8 weeks old; body weight, 23.8 ± 0.5 g) were randomly allocated to six groups (n = 10 per group): a control group (CON), a CTX model group (CTX), a levamisole-treated positive control group (PC), and low-, medium-, and high-dose SDF groups (125, 250, and 500 mg/kg body weight, respectively). Mice received oral administration of SDF or an equal volume of water for 21 consecutive days and were intraperitoneally injected with CTX (80 mg/kg body weight) on days 19–21 to induce intestinal injury. The results demonstrate that SDF possessed a porous, sponge-like network structure and comprised multiple monosaccharides. SDF intervention, particularly at medium and high doses, significantly attenuated CTX-induced body weight loss and immune organ atrophy; restored villus height and the villus-to-crypt ratio; increased the numbers of goblet cells and intraepithelial lymphocytes; elevated intestinal levels of sIgA, β-defensins, and lysozyme; and reduced serum levels of LPS, D-lactic acid, and DAO (p < 0.05). In conclusion, SDF derived from Polygonatum cyrtonema effectively mitigates CTX-induced intestinal injury by enhancing intestinal mucosal immunity and preserving intestinal barrier integrity, thereby highlighting its potential as a functional ingredient for promoting gut health. Full article

Background: Type 2 diabetes mellitus (T2DM) represents a pressing global health challenge, underscoring the urgency of developing effective dietary interventions derived from natural resources. Zaojiaomi polysaccharide (ZJMP) from the endosperm of Gleditsia sinensis seeds (zaojiaomi), a traditional edible product, exhibits largely underexplored potential in T2DM management. Methods: In the present study, the antidiabetic effects and underlying mechanisms of ZJMP were investigated using a rat model of T2DM induced by a high-fat diet (HFD) combined with streptozotocin (STZ). Relevant biochemical indicators were detected, and histopathological examination was performed. The expression levels of key components of the TLR4/MyD88/NF-κB signaling pathway, as well as the inflammatory cytokines IL-6 and IL-1β in renal tissues, were further analyzed. Additionally, gut microbiota composition and the levels of short-chain fatty acids were determined. Results: ZJMP treatment significantly ameliorated hyperglycemia and dyslipidemia, elevated serum insulin levels, reduced intestinal mucosal permeability, and attenuated histopathological lesions in the heart, kidney, and pancreas of T2DM rats. Meanwhile, ZJMP notably alleviated renal inflammation by suppressing the production of IL-1β and IL-6, as well as inhibiting the TLR4/MyD88/NF-κB pathway. Furthermore, ZJMP administration effectively modulated gut microbiota composition and increased fecal concentrations of acetic acid and propionic acid. Conclusions: Collectively, these findings elucidate the novel bioactivity of ZJMP and highlight its potential as a promising functional food ingredient or dietary supplement for T2DM management. Full article

Alterations in the intestinal microbiota have been implicated in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, their biological significance and therapeutic implications differ substantially between the two conditions. Although dysbiosis is a common feature, the mechanisms by which alterations in the microbiota contribute to disease pathophysiology and clinical expression are distinct. Some pathways are more prominent in IBS (e.g., the gut–brain axis), whereas others are more prominent in IBD (e.g., reduced microbial diversity). Equally important are pathways that appear to play a role exclusively in IBD [e.g., Adherent-invasive Escherichia coli (AIEC) and Paneth cells], as well as others that seem to be specific to IBS (e.g., mast cell activation). In IBD, microbiota changes are primarily linked to immune dysregulation, mucosal barrier impairment, and inflammation-driven pathways, whereas in IBS, they are mainly associated with functional disturbances mediated by neuroimmune signaling and microbial metabolites. Furthermore, several microbiome-associated biomarkers differ between these two diseases, and some are already assessed by international guidelines. Although the microbiota plays a key role in IBS and IBD pathophysiology, microbiome-based treatments remain limited, especially in IBD. There are clinically available treatments in IBS (e.g., rifaximin, low-FODMAP diet), but in IBD, only the probiotic VSL#3 is guideline-approved in ulcerative colitis pouchitis prophylaxis. Nevertheless, the dynamic nature of the microbiota continues to support the investigation of already studied (e.g., probiotics, fecal microbiota transplantation) and potential novel therapeutic approaches at the research level. The aim of this review is to compare the gut-microbiota-related pathophysiological pathways and biomarkers between IBS and IBD, to summarize the microbiome-related medications that have already been studied in both diseases, and to suggest new potential therapeutic options based on the gut microbiota. Full article

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Intestinal barrier impairment represents a core pathogenic mechanism and a key therapeutic target for achieving mucosal healing and sustained remission. Methods: This narrative review summarizes intestinal barrier structure, disruption mechanisms, barrier-targeted therapies, and non-invasive monitoring approaches. A reproducible literature search was conducted in PubMed, Web of Science, and ClinicalTrials.gov from 2015 to 2026. Results: Barrier disruption in UC involves genetic susceptibility, proinflammatory cytokines, zonulin-mediated tight junction injury, gut microbiota dysbiosis, decreased short-chain fatty acids and secondary bile acids, impaired autophagy, and an abnormal mucin 2 (MUC2)-dependent mucus layer. Validated non-invasive monitoring tools include fecal calprotectin/lactoferrin, intestinal ultrasound, diffusion-weighted magnetic resonance imaging (MRI), and intravoxel incoherent motion (IVIM). Emerging therapies focus on tight junction stabilization, epithelial regeneration, autophagy regulation, MUC2 restoration, and microbiota modulation. Conclusions: Intestinal barrier dysfunction drives the initiation and progression of UC. Barrier-based monitoring and targeted repair strategies improve UC management. Future studies should develop personalized therapies, precise microbiota engineering, and multi-dimensional digital evaluation systems. Full article

Background/Objectives: Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. Methods: This study investigated the impact of excessive dietary inorganic phosphate on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. Results: Pi overload induced atrophy in the thymus, spleen, and kidney; damaged the intestinal barrier; reduced the villus height-to-crypt-depth ratio; and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFN-α, indicated altered levels of immunoglobulins and cytokines under Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK/STAT pathway and metabolic regulators CPT1α and IDH1, when comparing Pi-treated mice with the control group. Conclusions: These preliminary findings suggest that Pi may affect intestinal mucosal barrier function and systemic immune response through immune regulation and mitochondrial metabolic pathways, providing preliminary insight into the potential health implications of Pi overconsumption in humans. Full article

The global incidence of nonalcoholic fatty liver disease (NAFLD) is rising, with no approved pharmacotherapy available. Medicinal plants offer a potential preventive strategy. Anacyclus pyrethrum root exhibits anti-inflammatory and glucose-regulating properties, but its role in NAFLD prevention is unclear. This study aims to investigate the preventive effect of Anacyclus pyrethrum root ethanol extract (APE) against NAFLD and its underlying mechanisms. The chemical composition of APE was analyzed by UHPLC-HRMS. Network pharmacology predicted the potential signaling pathways underlying its protective effects against NAFLD. In a 12-week high-fat diet mice model, APE treatment led to measurements of blood glucose, lipid profiles, liver function parameters, histopathological changes in liver and colon, and gut microbiota alterations via 16S rDNA sequencing. In animal experiments, APE lowered fasting and random blood glucose, total cholesterol, triglycerides, LDL-C, AST, ALT, and serum lipopolysaccharide while increasing HDL-C, and alleviated hepatic steatosis. Network pharmacology suggested APE acts via TLR, NF-κB, and TNF pathways. In vivo, APE suppressed hepatic TLR4, MyD88, p-NF-κB p65, the p-NF-κB p65/NF-κB p65 ratio, and TNF-α/IL-6 levels. Gut microbiota analysis showed increased Akkermansiaceae and decreased Desulfovibrionaceae. APE also upregulated intestinal Occludin and ZO-1, and downregulated intestinal TNF-α and IL-6. APE prevents NAFLD progression, potentially by regulating gut microbiota, protecting the intestinal mucosal barrier, and inhibiting the LPS/TLR4/MyD88/NF-κB pathway. Full article

Background/Objectives: Recent studies have shown that GABA reduces visceral hypersensitivity and improves intestinal permeability in a post-inflammatory irritable bowel syndrome (IBS) rat model. We aimed to assess the efficacy of a GABA-based supplement in IBS patients with diarrhea (IBS-D), focusing on symptoms relief, quality-of-life improvement, mucosal barrier function, systemic microinflammation and gut microbiota. Methods: In this double-blind, placebo-controlled, crossover study, 20 IBS-D patients were randomized to receive GABA or placebo for two four-week treatment periods separated by a two-week washout. Efficacy was assessed using IBS Symptom Severity Score (IBS-SSS) and Short-Form Health Survey-36 (SF-36). Circulating levels of lipopolysaccharide-binding protein (LBP), Tumor Necrosis Factor-α (TNF-α) and interleukin (IL)-1β were measured before and after each treatment. Results: Eighteen patients completed the study. A clinical response (≥50-point reduction in IBS-SSS) was observed in 66.7% of patients during GABA treatment versus 33.3% with placebo. GABA produced a significant reduction in the IBS-SSS total score (p = 0.02) and in the bowel satisfaction item of the questionnaire (p = 0.02). Regarding quality of life, GABA significantly improved the “Emotional limitation” domain compared with placebo (p = 0.009). GABA treatment also led to a decrease in circulating LBP (p = 0.06) and IL-1β (p = 0.02) levels compared to placebo, although only the reduction in IL-1β reached statistical significance. In contrast, no substantial remodeling of the gut microbiota was observed. Conclusions: In this pilot study, GABA treatment led to a significant improvement in IBS-D symptoms compared with placebo and was also more effective in enhancing emotional wellbeing. GABA appeared to have a possible effect on intestinal permeability indirectly assessed through LBP, consistent with preclinical findings, and significantly reduced systemic inflammation. GABA may represent a promising therapeutic option for IBS, deserving further investigation in larger clinical trials. Full article

Background: Functional dyspepsia (FD) is a disorder of gut–brain interaction characterized by heterogeneous pathophysiological mechanisms, including altered gastric motility, visceral hypersensitivity, low-grade inflammation, impaired mucosal defence, and oxidative stress. Multi-target botanical strategies may represent a rational approach for addressing this complexity. Methods: This study evaluated the mechanistic rationale supporting a botanical formulation containing Zingiber officinale, Cynara scolymus, and Citrus limon extracts, here referred to as DyspepCyn^®. A focused narrative review was conducted to summarize the available mechanistic and clinical evidence for the three botanicals. In addition, the formulation was characterized through solubility testing in aqueous and biorelevant simulated gastrointestinal media, together with antioxidant assessment using ORAC and DPPH assays. Results: DyspepCyn^® showed favourable dispersion and solubility behaviour across simulated gastrointestinal conditions, with complete solubilization up to approximately 700 mg/100 mL in water and up to approximately 800 mg/100 mL in simulated intestinal fluids. No precipitation was observed in the tested media. The formulation also showed measurable antioxidant activity, with an ORAC value of 365 µmol Trolox equivalents/g and a DPPH radical scavenging EC₅₀ of 32 µg/mL. Conclusions: DyspepCyn^® combines botanicals with complementary actions on gastric motility, postprandial digestive processes, mucosal protection, and oxidative stress. The observed physicochemical stability and antioxidant capacity support the mechanistic rationale for this multi-target botanical strategy in FD. Clinical studies are required to confirm its efficacy in patients with FD. Full article

The gastrointestinal (GI) barrier is a highly coordinated, multilayered defence system that maintains intestinal homeostasis by separating the luminal microbiota from the internal milieu. In liver cirrhosis, this barrier undergoes profound structural and functional disruption, emerging as a central driver of bacterial translocation and infection-related complications. Among these, spontaneous bacterial peritonitis (SBP) represents a major determinant of morbidity, mortality, and disease progression. Barrier failure in cirrhosis is not attributable to a single defect but results from the convergence of multiple interconnected mechanisms. Structural alterations include disruption of epithelial tight junctions and deterioration of the mucus layer, leading to increased intestinal permeability and loss of spatial compartmentalisation. These changes are compounded by microbial dysbiosis, characterised by reduced diversity, depletion of short-chain fatty acid-producing taxa, and expansion of pathobionts. In parallel, cirrhosis-associated immune dysfunction impairs both mucosal and systemic antimicrobial defences, while gut–vascular barrier disruption facilitates systemic dissemination of bacteria and microbial products. The resulting increase in bacterial translocation plays a pivotal role in the pathogenesis of SBP and contributes to systemic inflammation, circulatory dysfunction, and acute decompensation. Importantly, this process establishes a self-amplifying pathogenic loop in which barrier dysfunction, dysbiosis, and immune dysregulation mutually reinforce each other. Recent advances have identified key molecular pathways involved in barrier regulation, including bile acid–FXR signalling and microbiome-derived metabolites, providing novel targets for therapeutic intervention. While current management relies largely on antibiotics and supportive care, emerging strategies aim to restore barrier integrity and modulate the gut–liver axis. A deeper understanding of GI barrier dysfunction offers new opportunities to prevent bacterial translocation and improve clinical outcomes in patients with liver cirrhosis. Full article