Intestinal Inflammation Research Articles

Evidence for a Modulatory Effect of a 12-Week Pomegranate Juice Intervention on the Transcriptional Response in Inflammatory Bowel Disease Patients Reducing Fecal Calprotectin Levels: Findings From a Proof-of-Principle Study.

This study aimed at investigating the effects of pomegranate juice (POMJ) consumption on inflammatory biomarkers and gene expression in patients with inflammatory bowel disease (IBD) in clinical remission. In this randomized, placebo-controlled trial, 16 subjects with IBD in remission consumed POMJ or placebo for 12 weeks. POMJ consumption significantly reduced fecal calprotectin (FC) and plasma endotoxin levels. Transcriptomic analysis of peripheral blood mononuclear cells revealed upregulation of genes involved in mucosal immunity, including aryl hydrocarbon receptor (AHR), neutrophil cytosolic factor 4 (NCF4), and nuclear factor, interleukin 3 regulated (NFIL3). Urolithin metabotypes were predominantly of the B type, associated with intestinal dysbiosis. No significant changes were observed in serum inflammatory markers or colonic mucosal cytokine expression. POMJ consumption reduced markers of intestinal inflammation and modulated gene expression related to mucosal immunity and barrier function in patients with IBD. These findings suggest the potential of POMJ as a beneficial dietary intervention for maintaining remission in IBD, highlighting the promise of targeted nutritional strategies in managing chronic inflammatory conditions. Further research is needed to elucidate the long-term clinical implications of these molecular changes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03000101.

Maslinic Acid Ameliorates DSS-Induced Experimental Colitis by Suppressing Th Cell-Mediated Inflammation via AICD Induction.

Ulcerative colitis (UC) is a nonspecific chronic inflammatory disease that occurs in the gastrointestinal tract and is characterized by the breakdown of mucosal immunity. T helper (Th) cells paradigm disequilibrium is a critical for pathogenesis. Maslinic acid (MA), a naturally occurring pentacyclic triterpene isolated from olive pomace and Fructus crataegi, has a variety of applications in both medicine and food. This study investigated the molecular mechanism of the anti-inflammatory potential of MA in a colitis model and activated Th cells. A dextran sulfate sodium-induced experimental colitis model was established. Clinical symptoms were evaluated, and biological samples were collected to examine intestinal mucosal function, inflammation levels, and Th cell-mediated immune responses. The mechanism of the activation-induced cell death (AICD) effect regulated by MA was investigated in the anti-CD3ε/CD28-stimulated Th cell activation model using molecular biotechnology and transcriptome analysis. Key results:MA treatment protected intestinal mucosa, which manifested as reduced inflammatory cytokines, Th cell infiltration, and subset differentiation. Additionally, it was found to suppress Th cell proliferation and differentiation of subsets, regulate cell cycle distribution, and promote AICD by regulating the mitochondria-mediated intrinsic pathway invitro. JAK-STAT and FcεRI pathways were probable essential pathways, and MAF might be a crucial potential targeting molecule in activated Th cells with MA treatment. This finding demonstrated that MA induced remission of the colitis-related inflammation, which may depend on the resolution of acute inflammation by reducing Th cell-mediated inflammation via AICD induction, emphasizing its promising potential in the treatment of UC.

Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation

Ulcerative colitis (UC) is a complex and chronic inflammatory bowel disease whose pathogenesis involves genetic and environmental factors, which poses a challenge for treatment. Here, we have designed an innovative integrated therapeutic strategy using Lactobacillus acidophilus extracellular vesicles (EVs) to encapsulate UiO-66-NH2 nanoparticles bounded with TNF-α siRNA (EVs@UiO-66-NH2@siRNA) for UC treatment. This system shows superior affinity to inflammation-related cells due to the Lactobacillus acidophilus EVs can maintain immune homeostasis by regulating the secretion of cytokines in vitro. siRNA can specifically target the key inflammatory TNF-α in UC and silence its gene expression, thereby regulating the process of inflammatory response. After oral administration, EVs@UiO-66-NH2@siRNA demonstrates an accurate delivery of TNF-α siRNA to colonize the colon site and exerts a siRNA therapeutic effect by inhibiting the expression of TNF-α, which alleviates the intestinal inflammation in DSS-induced UC model. Moreover, this system can modulate the types and compositional structures of gut microbiota and metabolites to achieve an anti-inflammatory phenotype, which is helpful for the repair of intestinal homeostasis. We also have proved that UiO-66-NH2 nanoparticles exhibit a high loading capacity for TNF-α siRNA and good pH responsiveness, improving the potent release of siRNA in colon tissue. Collectively, the EVs@UiO-66-NH2@siRNA nano-delivery system demonstrate a feasible combination therapeutic strategy for UC through gut microecology modulation, immune regulation and TNF-α siRNA silence, which may provide a potential targeted treatment approach for inflammatory bowel disease.Graphical

Six Weeks of Moderate-Intensity Treadmill Exercise Improves Intestinal Barrier and Intestinal Inflammation in Parkinson's Disease Mice.

More than 80% of patients with Parkinson's disease (PD) exhibit severe gastrointestinal symptoms, which seriously affect life quality of life. Several large-scale epidemiological studies have confirmed that exercise can improve motor symptoms of PD patients, but the influence on gastrointestinal symptoms has not been reported. To clarify whether exercise can enhance intestinal barrier and ameliorate intestinal inflammation in PD mice, we examined whether moderate-intensity treadmill exercise for 6weeks could alleviate gastrointestinal symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute PD mice. Our results demonstrated that 6weeks moderate-intensity treadmill exercise enhanced the expression of Muc-2 and tight junction proteins, while reducing the expression of cytokines and chemokines, in the distal colon. Moreover, 6weeks of treadmill exercise reduced the concentrations of short-chain fatty acids (SCFAs) and the expression of G protein-coupled receptor 43 (GPR43) to maintain the intestinal barrier and alleviate intestinal inflammation. Further data showed that 6weeks of moderate-intensity treadmill exercise enhanced insulin-like growth factor 1 (IGF-1) expression and activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Taken as a whole, these results revealed that 6weeks of moderate-intensity treadmill exercise enhanced intestinal barrier function, reduced intestinal inflammation and corrected abnormal concentrations of SCFAs by activating IGF-1/PI3K/Akt pathway in MPTP-induced subacute PD mice.

Spontaneous Ileitis and Post-Surgical Murine Models of Enteric Hyperoxaluria.

Enteric hyperoxaluria, a risk factor for kidney stone disease, often arises from malabsorptive bariatric surgeries or inflammatory bowel diseases. Current murine models for studying this condition are limited, necessitating new approaches. This study aims to establish two novel and distinct mouse models to investigate enteric hyperoxaluria: one simulating Roux-en-Y gastric bypass surgery and the other Crohn's ileitis. In the first model, diet-induced obese C57BL/6J male mice underwent either sham or bypass surgery, followed by three weeks on a high-fat, oxalate-enriched diet. In the second model, SAMP1/YitFc and AKR mice were gradually introduced to high-fat diets, later supplemented with oxalate while reducing fat content. Samples of urine, blood, and feces were collected to assess oxalate, creatinine, and fecal lipid profiles. Results showed hyperoxaluria and increased stool fat content, indicating fat malabsorption, in both SAMP1 and bypass mice compared to controls. Kidney injury was also observed. These findings confirm the successful establishment of enteric hyperoxaluria in both models, highlighting the role of dietary oxalate, intestinal inflammation, and fat malabsorption in disease progression. These models provide valuable tools for exploring cellular and molecular mechanisms in enteric hyperoxaluria and may inform future therapeutic strategies.

Sodium butyrate attenuates experimental neonatal necrotizing enterocolitis by suppressing TLR4-mediated NLRP3 inflammasome-dependent pyroptosis.

Necrotizing enterocolitis (NEC) is a fatal intestinal disease in premature infants, and is characterized by intestinal inflammation and disruption of the intestinal barrier. The protective effects of sodium butyrate (NaB) against NEC have been documented, however, the underlying fundamental processes remain unknown. To address this deficit, we used the NEC neonatal rat model to confirm the intestinal protective effect of NaB. We then used network pharmacology and confirmed a role for NaB in the attenuation of NEC and this was associated with the NLRP3 inflammasome and the NF-κB signaling pathway. These results were verified by proteome analysis in vivo, and molecular docking analysis was used to explore the potential underlying mechanisms, revealing a suppressive function of NaB on NEC, which may be caused by its interaction with the TLR4-mediated NF-κB signaling pathway. An in vitro cell model (LPS-stimulated IEC-6 cells) was then established to confirm the docking results. Results using assays involving the NLRP3 (MCC950) and TLR4 (TAK-242) inhibitors suggested that NaB protected intestinal cells from inflammatory injuries during NEC by suppressing the TLR4/MyD88/NF-κB/NLRP3/cleaved caspase-1/GSDMD inflammasome pathway. These findings indicated that NaB can be used as a potential modulatory and therapeutic candidate for the treatment of NEC.

DSS-induced colitis exacerbates Alzheimer's pathology via neutrophil elastase and cathepsin B activation.

DSS-induced colitis exacerbates Alzheimer's pathology via neutrophil elastase and cathepsin B activation.

Advances in Artificial Intelligence and Machine Learning for Precision Medicine in Necrotizing Enterocolitis and Neonatal Sepsis: A State-of-the-Art Review

Necrotizing enterocolitis remains one of the most severe gastrointestinal diseases in neonates, particularly affecting preterm infants. It is characterized by intestinal inflammation and necrosis, with significant morbidity and mortality despite advancements in neonatal care. Recent advancements in artificial intelligence (AI) and machine learning (ML) have shown potential in improving NEC prediction, early diagnosis, and management. A systematic search was conducted across multiple databases to explore the application of AI and ML in predicting NEC risk, diagnosing the condition at early stages, and optimizing treatment strategies.AI-based models demonstrated enhanced accuracy in NEC risk stratification compared to traditional clinical approaches. Machine learning algorithms identified novel biomarkers associated with disease onset and severity. Additionally, deep learning applied to medical imaging improved NEC diagnosis by detecting abnormalities earlier than conventional methods. The integration of AI and ML in NEC research provides promising insights into patient-specific risk assessment. However, challenges such as data heterogeneity, model interpretability, and the need for large-scale validation studies remain. Future research should focus on translating AI-driven findings into clinical practice, ensuring ethical considerations and regulatory compliance.

Comprehensive analysis of faecal metagenomic and serum metabolism revealed the role of gut microbes and related metabolites in detecting colorectal lateral spreading tumours

ABSTRACT Colorectal lateral spreading tumours (LST), early-stage lesions of colorectal cancer (CRC), are associated with gut microbiota dysbiosis. However, the functional alterations in gut microbiota and their metabolic pathways remain inadequately understood. This study employed propensity score matching to compare 35 LST patients with 35 healthy controls. Metagenomic and metabolomic analyses revealed notable differences in gut microbiota composition and metabolic pathways. LST patients exhibited a marked reduction in short-chain fatty acid (SCFA)-producing probiotics, such as Roseburia, Clostridium, and Butyricicoccus sp-OF13–6, alongside anti-inflammatory metabolites. In contrast, potential intestinal pathogens linked to inflammatory bowel disease (IBD), including Escherichia and Citrobacter amalonaticus, were significantly enriched. Orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted significant metabolic disparities between the groups, with enrichment in pathways associated with cholesterol metabolism, choline metabolism in cancer, and amino acid metabolism – all relevant to cancer progression. Key biomarkers identified for LST included fumarate, succinate, glutamic acid, glycine, and L-aspartic acid, which were closely linked to these pathways. Functional studies demonstrated that these metabolites promoted the proliferation and invasion of HCT-116 and SW480 human colorectal cancer cells in vitro. Metagenomic and metabolomic analysis revealed a strong positive correlation between Escherichia and Ruminococcus sp-AM41-2AC abundance and the enriched pathways, whereas reductions in Roseburia species, including Roseburia-OF03–24 and Roseburia intestinalis_CAG13—exhibited negative correlations. These results suggest that gut microbiota and metabolite alterations in LST contribute to intestinal inflammation and CRC development, underscoring their potential as biomarkers for early detection and therapeutic targets.

NUDT1 aggravates intestinal epithelial barrier injury through oxidative stress in ulcerative colitis.

NUDT1 aggravates intestinal epithelial barrier injury through oxidative stress in ulcerative colitis.

Filamentous bacteriophage M13 induces proinflammatory responses in intestinal epithelial cells.

Bacteriophages are the dominant members of the human enteric virome and can shape bacterial communities in the gut; however, our understanding of how they directly impact health and disease is limited. Previous studies have shown that specific bacteriophage populations are expanded in patients with Crohn's disease (CD) and ulcerative colitis (UC), suggesting that fluctuations in the enteric virome may contribute to intestinal inflammation. Based on these studies, we hypothesized that a high bacteriophage burden directly induces intestinal epithelial responses. We found that filamentous bacteriophages M13 and Fd induced dose-dependent IL-8 expression in the human intestinal epithelial cell line HT-29 to a greater degree than their lytic counterparts, T4 and ϕX174. We also found that M13, but not Fd, reduced bacterial internalization in HT-29 cells. This led us to investigate the mechanism underlying M13-mediated inhibition of bacterial internalization by examining the antiviral and antimicrobial responses in these cells. M13 upregulated type I and III IFN expressions and augmented short-chain fatty acid (SCFA)-mediated LL-37 expression in HT-29 cells. Taken together, our data establish that filamentous bacteriophages directly affect human intestinal epithelial cells. These results provide new insights into the complex interactions between bacteriophages and the intestinal mucosa, which may underlie disease pathogenesis.

Baseline abundance of Akkermansia muciniphila and Bacteroides acidifaciens in a healthy state predicts inflammation associated tumorigenesis in the AOM/DSS mouse model

Numerous studies demonstrate that intestinal microbiota contribute to colorectal cancer (CRC), which is often associated with dysbiosis. Most of the data were obtained from studies on CRC patients, making it challenging to determine whether alterations in microbiota are a consequence of the pathology or whether they actively drive its progression. Several studies using laboratory animals suggest that gut microbiota may be involved in both the onset and progression of CRC. In the present study we utilized the azoxymethane-dextran sulfate sodium (AOM/DSS) mouse model of CRC to investigate the contribution of healthy-state microbiota to inflammation-associated tumorigenesis. Two cohorts of C57BL/6 mice harboring different intestinal microbiota demonstrated different susceptibility to AOM/DSS treatment. Sequencing of 16S rRNA bacterial DNA from fecal samples revealed Akkermansia muciniphila and Bacteroides acidifaciens as marker features in the healthy-state microbiota (before AOM/DSS administration), which showed a strong positive correlation with tumor incidence. Moreover, the healthy-state abundance of these markers, considered beneficial bacteria, was strongly positively correlated with the sulfate-reducing bacteria Desulfovibrio fairfieldensis identified as a marker of chronic colitis-associated microbiota. Furthermore, the abundances of these marker features, associated with CRC outcome, correlated with the expression of interferon gamma and nitric oxide synthase 2 genes in colon tissue during the early stage of DSS-induced intestinal inflammation. In contrast to multiple studies demonstrating the anti-inflammatory properties of A. muciniphila and B. acidifaciens, our results point out their potential adverse effect under specific conditions of genotoxicity and inflammation in the intestine. Taken together, our findings suggest a complex, context-dependent role of commensal microbiota in inflammation-associated dysbiosis and CRC.

Self-disassembling nanoparticles as oral nanotherapeutics targeting intestinal microenvironment

Inspired by the survival strategies of pyomelanin-producing microbes, we synthesize pyomelanin nanoparticles (PMNPs) from homogentisic acid- γ-lactone via auto-oxidation and investigate their biomedical potential. PMNPs possess distinct physicochemical properties, including reactive oxygen species scavenging and microenvironment-responsive self-disassembly. Under intestinal conditions, PMNPs self-disassemble and penetrate the nanoscale pores of the mucin layer. In an inflammatory bowel disease model, orally administered PMNPs withstand gastric acidity and, in their solubilized form, interact with macrophages and epithelial cells. They significantly reduce reactive oxygen species levels, exert anti-inflammatory effects, and restore gut microbiota composition. Compared to conventional nanoparticles and 5-aminosalicylic acid, PMNPs exhibit greater therapeutic efficacy. Clinical symptoms and intestinal inflammation are alleviated, and the gut microbiota is restored to near-normal levels. These findings underscore the therapeutic potential of PMNPs for inflammatory bowel disease treatment and suggest broader biomedical applications.

The effects of probiotic treatment with Bifidobacterium breve, Bif195 for small intestinal Crohn’s disease and the gut microbiome: results from a randomised, double-blind, placebo-controlled trial

BackgroundThe aetiology of Crohn’s disease, a chronic inflammatory bowel disease, is multifactorial and not completely understood. However, the association with gut dysbiosis is well-established, and manipulation of the gut microbiota has gained interest as a treatment strategy. This study aimed to investigate the effects of the probiotic strain Bifidobacterium breve, Bif195™ (Bif195) on intestinal inflammation, symptoms, and the gut microbiome composition in patients with small intestinal Crohn’s disease.MethodsThis was a randomised, double-blind, placebo-controlled trial. Thirty-three patients with small intestinal Crohn’s disease were assigned to eight weeks of treatment with Bif195 or placebo (1:1). The primary outcome was changes in bowel wall thickness measured by intestinal ultrasonography. Other outcomes were changes in symptom severity, quality of life, faecal calprotectin, fatigue, and specific inflammatory parameters on ultrasonography. Changes in the microbiome composition were also examined.ResultsBif195 did not affect the bowel wall thickness in the small intestine compared to placebo. Nor did we observe effects on secondary or clinical explorative outcomes. Analysis of the gut microbiome showed that the relative abundance of B. breve rose during the intervention in the Bif195 group, but the result was statistically non-significant. Surprisingly, we observed a clustering of baseline microbiome data into two groups that differed in several aspects including a statistically significant difference in the incidence of previous bowel resections among the participants. Furthermore, changes in symptom scores after eight weeks of intervention were significantly different across the two microbiome groups, with an interaction effect of p = 0.04.ConclusionsEight weeks of treatment with Bif195 did not affect clinical outcomes for Crohn’s disease. However, variations in baseline microbiome data influenced the results. This underscores the importance of assessing baseline microbiome data in intervention studies in Crohn’s disease.Clinicaltrials.gov NCT04842149

The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.

Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.

Regulation of pyroptosis by natural products in ulcerative colitis: mechanisms and therapeutic potential

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is driven by dysregulated immune responses and persistent intestinal inflammation. Pyroptosis, a caspase/gasdermin-mediated inflammatory cell death that exacerbates mucosal damage through excessive cytokine release and epithelial barrier disruption. Although pyroptosis is considered to be a key mechanism in the pathogenesis of UC, the systematic assessment of the role of natural products in targeting the pyroptosis pathway remains a critical research gap. The purpose of this review is to investigate the regulatory effects of natural products on pyroptosis in UC and elucidate the mechanisms of action and potential therapeutic effects. Key findings highlight polyphenols (e.g., resveratrol), flavonoids (e.g., Quercetin), and terpenoids as promising agents that inhibit NLRP3 inflammasome activation, suppress gasdermin D cleavage, and restore barrier integrity, thereby reducing pro-inflammatory cytokine release in preclinical UC models. Current evidence shows enhanced efficacy and safety when these compounds are combined with standard therapies, but clinical translation requires overcoming three key barriers: limited human trial data, uncharacterized polypharmacology, and suboptimal pharmacokinetics needing formulation refinement. Future research should prioritize standardized animal-to-human translational models, mechanistic studies on synergistic pathways, and rigorous clinical validation to harness the full potential of natural products in pyroptosis-targeted UC therapies.

Electroacupuncture modulates the gut-brain axis via the PI3K/Akt pathway to improve feeding behavior, body weight, glucolipid metabolism, and reduce insulin resistance in T2DM rats

BackgroundThe rising prevalence and high mortality of diabetes have made it a significant public health concern. This study explores how electroacupuncture (EA) influences the PI3K/Akt pathway and its role in regulating the gut-brain axis, focusing on whether EA can modulate this axis via the PI3K/Akt pathway in the treatment of type 2 diabetes mellitus (T2DM). The research aims to reveal the mechanisms underlying EA’s therapeutic effects and to investigate a novel strategy for managing T2DM.MethodsTo induce T2DM in rat models, a high-fat diet and intraperitoneal injection of streptozotocin (STZ) were used. The rats were then randomly divided into four groups: a T2DM group, an EA group, an EA plus PI3K inhibitor group (EA + LY294002), and a control group (Con), which received a standard diet and a citric acid-sodium citrate solution. Following five weeks of intervention, assessments were conducted for food intake, body weight, fasting blood glucose (FBG), blood lipid profiles, and insulin resistance (IR). To analyze the PI3K/Akt pathway and gut-brain axis indices, various methods were employed, including Western blotting, qPCR, immunohistochemistry staining, HE staining, and 16 S rRNA sequencing.ResultsOur research shows that EA improves food intake, body weight, FBG, lipid levels (TC, TG, HDL, LDL), serum insulin levels, IR and insulin sensitivity indices in T2DM rats. Additionally, EA boosts the expression of colonic tight junction proteins ZO-1, Occludin, and Claudin-1 while reducing intestinal inflammation and intestinal cell apoptosis. It also regulates Ghrelin and PYY levels in both colonic and hypothalamic tissues, improving the gut microbiota structure. These effects can be reversed by PI3K inhibitors.ConclusionsEA plays a role in managing feeding behavior, body weight, and glucolipid metabolism, as well as alleviating IR in T2DM rats. EA may contribute to the preservation of intestinal mucosal barrier integrity, likely through anti-inflammatory and anti-apoptotic actions mediated by the PI3K/Akt pathway. Additionally, EA appears to influence the regulation of brain-gut peptides and promote a healthier gut microbiota composition. These findings suggest that EA holds potential as an therapeutic approach for T2DM, with its mechanisms potentially linked to the modulation of the gut-brain axis via the PI3K/Akt pathway. Further research is warranted to fully elucidate these effects and their clinical implications.

Mechanisms of Baicalin Alleviates Intestinal Inflammation: Role of M1 Macrophage Polarization and Lactobacillus amylovorus.

Baicalin has been widely used for its anti-inflammatory pharmacological properties, yet its effects on bacterial intestinal inflammation and the mechanisms remain unclear. This study revealed that baicalin alleviates bacterial intestinal inflammation through regulating macrophage polarization and increasing Lactobacillus amylovorus abundance in colon. Specifically, transcriptomic analysis showed that baicalin restored Escherichia coli-induced genes expression changes including T helper cell 17 differentiation-related genes, macrophage polarization related genes, and TLR/IRF/STAT signaling pathway. Subsequent microbial and non-targeted metabolomic analysis revealed that these changes may be related to the enhancement of Lactobacillus amylovorus and the upregulation of its metabolites including chrysin, lactic acid, and indoles. Furthermore, whole-genome sequencing of Lactobacillus amylovorus provided insights into its functional potential and metabolic annotations. Lactobacillus amylovorus supplementation alleviates Escherichia coli-induced intestinal inflammation in mice and similarly inhibited M1 macrophage polarization through TLR4/IRF/STAT pathway. Additionally, baicalin, Lactobacillus amylovorus, or chrysin alone could regulate macrophage polarization, highlighting their independent anti-inflammatory potential. Notably, this study revealed that baicalin alleviates intestinal inflammation through TLR4/IRF/STAT pathway and increasing Lactobacillus amylovorus abundance and the synthesis of chrysin. These findings provide new insights into the therapeutic potential of baicalin and Lactobacillus amylovorus in preventing and treating intestinal inflammation, offering key targets for future interventions.

Gut microbiota contributes to protection against porcine deltacoronavirus infection in piglets by modulating intestinal barrier and microbiome

BackgroundGut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.ResultsFirstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.ConclusionsPDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses.A86XHQd7Nui-t9JMrkxd7oVideo

TL1A/DR3 signaling regulates the generation of pathogenic Th9 cells in experimental Crohn's disease.

TL1A/DR3 signaling regulates the generation of pathogenic Th9 cells in experimental Crohn's disease.