Porcine epidemic diarrhea (PED) incurs substantial economic losses to the pig industry. During viral infection of cells, the activity of NF-κB is upregulated. As an endogenous inhibitor, FoxO4 plays a crucial role in antagonizing NF-κB activity, inhibiting the NF-κB-mediated MLCK signaling pathway, altering the expression of cellular tight junctions (TJs) and pro-inflammatory cytokines, and protecting intestinal epithelial cells from damage. However, there are limited reports on this inhibitory and protective effect in PEDV-infected IPEC-J2 cells. Therefore, this experiment employed methods such as homologous recombination, qRT-PCR, Western blotting, co-immunoprecipitation, laser confocal microscopy, and cell transmembrane resistance assays to investigate the effect of FoxO4 on indicators related to cell damage through the NF-κB/MLCK pathway in infected cells. The results demonstrated the successful construction of FoxO4 and NF-κB factor p65 expression vectors, confirming the interaction between the two in IPEC-J2 cells. FoxO4 effectively antagonizes the expression of NF-κB/MLCK pathway factors in infected cells, and through this action, it reduces the permeability of infected cells, maintains the integrity of the cell membrane, upregulates the expression of TJ proteins, antagonizes the expression of pro-inflamma-tory factors, and exerts effects in promoting cell apoptosis and antagonizing viral replication.This study further elucidates the molecular mechanisms underlying cell damage caused by PEDV and offers new potential targets for protecting intestinal epithelial barrier function.

A mutualistic co-evolution exists between the host and its associated microbiota in the human body. Bacteria establish ecological niches in various tissues of the body, locally influencing their physiology and functions, but also contributing to the well-being of the whole organism through systemic communication with other distant niches (axis). Emerging evidence indicates that when the composition of the microbiota inhabiting the niche changes toward a pathogenic state (dysbiosis) and interactions with the host become unbalanced, diseases may present. In addition, imbalances within a single niche can cause dysbiosis in distant organs. Current research efforts are focused on elucidating the mechanisms leading to dysbiosis, with the goal of restoring tissue homeostasis. In vitro models can provide critical experimental platforms to address this need, by reproducing the niche cyto-architecture and physiology with high fidelity. This review surveys current in in vitro host-microbiota research strategies and provides a roadmap that can guide the field in further developing physiologically relevant in vitro models of ecological niches, thus enabling investigation of the role of the microbiota in human health and diseases. Lastly, given the Food and Drug Administration Modernization Act 2.0, this review highlights emerging in vitro strategies to support the development and validation of new therapies on the market.

Inflammatory bowel disease (IBD) is a chronic disease that is related to excessive inflammation and an imbalance in the gut microbiota. In this study, the effect of five Bifidobacterium longum subsp. longum strains on alleviating the colitis induced by dextran sulfate sodium (DSS) was investigated. Disease activity index (DAI) scores combined with hematoxylin and eosin (H&E) analysis showed that only B. longum BL300 could significantly alleviate DSS-induced colitis. Furthermore, immunofluorescence analysis confirmed that the expression of the intestinal barrier-related protein ZO-1, occludin, claudin-1 and MUC2 was significantly up-regulated. Moreover, transcriptome analysis of the colon tissue combined with RT-qPCR analysis revealed that levels of pro-inflammatory cytokines IL-2, IL-6, IL-17, TNF-α and IL-1β were decreased and anti-inflammatory cytokine IL-10 level was increased after B. longum BL300 intervention. Notably, the IgA production immune network was activated by B. longum BL300, which eliminated pathogenic bacteria, such as Escherichia, Shigella, Enterobacter and Prosthecobacter, by forming complexes. Meanwhile, the relative abundance of SCFA-producing bacteria was significantly increased. These results highlight the anti-inflammatory effect of B. longum BL300 on DSS-induced colitis, indicating its use as a probiotic candidate to support recovery from ongoing colitis.

Probiotics have been established to exert a positive impact on the treatment of various diseases. Indeed, these active microorganisms have garnered significant attention in recent years for their potential to prevent and treat illnesses. Their beneficial effects have been hypothesized to be linked to their released extracellular vesicles. These nanoscale structures, secreted during the growth and metabolism of probiotics, possess favorable biocompatibility and targeting properties, thereby promoting intercellular material transport and signaling. This article aimed to review the bioactive components and functions of these probiotics vesicles, highlighting their role in the treatment of various diseases and discussing their potential future applications. By exploring the mechanisms of probiotic extracellular vesicles in disease development, this review aimed to provide a theoretical reference for further research on their therapeutic potential. © 2025 Society of Chemical Industry.

The gastrointestinal (GI) tract plays a critical role in nutrient absorption, immune responses, and overall health. Traditional models such as two-dimensional cell cultures have provided valuable insights but fail to replicate the dynamic and complex microenvironment of the human gut. Gut-on-a-chip platforms, which incorporate cells located in the gut into microfluidic devices that simulate peristaltic motion and fluid flow, represent a significant advancement in modeling GI physiology and diseases. This review discusses the evolution of gut-on-a-chip technology, from simple cellular mono-cultures models to more sophisticated systems incorporating bi-cultures and tri-cultures that enable studies of drug metabolism, disease modeling, and gut-microbiome interactions. Although challenges remain, including maintaining long-term cell viability and replicating immune responses, these platforms hold great potential for advancing personalized medicine and improving drug discovery efforts targeting gastrointestinal disorders.

Chronic metabolic inflammation is a common mechanism linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease (CVD). Chronic metabolic inflammation often related to alterations in gut homeostasis, and pathological processes involve the activation of endotoxin receptors, metabolic reprogramming, mitochondrial dysfunction, and disruption of intestinal nuclear receptor activity. Recent investigations into homeostasis and chronic metabolic inflammation have revealed a novel mechanism which is characterized by a timing interaction involving multiple components and targets. This article explores the positive impact of tea consumption on metabolic health of populations, with a special focus on the improvement of inflammatory indicators and the regulation of gut microbiota. Studies showed that tea consumption is related to the enrichment of gut microbiota. The relative proportion of Firmicutes/Bacteroidetes (F/B) is altered, while the abundance of Lactobacillus, Bifidobacterium, and A. muciniphila increased significantly in most of the studies. Thus, tea consumption could provide potential protection from the development of chronic diseases by improving gut homeostasis and reducing chronic metabolic inflammation. The direct impact of tea on intestinal homeostasis primarily targets lipopolysaccharide (LPS)-related pathways. This includes reducing the synthesis of intestinal LPS, inhibiting LPS translocation, and preventing the binding of LPS to TLR4 receptors to block downstream inflammatory pathways. The TLR4/MyD88/NF-κB p65 pathway is crucial for anti-metaflammatory responses. The antioxidant properties of tea are linked to enhancing mitochondrial function and mitigating mitochondria-related inflammation by eliminating free radicals, inhibiting NLRP3 inflammasomes, and modulating Nrf2/ARE activity. Tea also contributes to safeguarding the intestinal barrier through various mechanisms, such as promoting the synthesis of short-chain fatty acids in the intestine, activating intestinal aryl hydrocarbon receptor (AhR) and farnesoid X receptor (FXR), and improving enteritis. Functional components that improve chronic metabolic inflammation include tea polyphenols, tea pigments, TPS, etc. Tea metabolites such as 4-Hydroxyphenylacetic acid and 3,4-Dihydroxyflavan derivatives, etc., also contribute to anti-chronic metabolic inflammation effects of tea consumption. The raw materials and processing technologies affect the functional component compositions of tea; therefore, consuming different types of tea may result in varying action characteristics and mechanisms. However, there is currently limited elaboration on this aspect. Future research should conduct in-depth studies on the mechanism of tea and its functional components in improving chronic metabolic inflammation. Researchers should pay attention to whether there are interactions between tea and other foods or drugs, explore safe and effective usage and dosage, and investigate whether there are individual differences in the tea-drinking population leading to different effects of tea intervention. Ultimately, the application of tea drinking could be a universal therapy for regulating intestinal homeostasis, anti-chronic metabolic inflammatory responses, and promoting metabolic health.

Disruption of the circadian clock is associated with the development of inflammatory bowel disease (IBD), but the underlying mechanisms remain unclear. Here, we observe that mice in the early active phase (Zeitgeber time 12, ZT12) of the circadian clock are more tolerant to dextran sodium sulfate (DSS)-induced colitis, compared to those in the early resting phase (ZT0). The expression of the circadian gene Bmal1 peaks in the early resting phase and declines in the early active phase. Bmal1 knockout in the intestinal epithelium reduces DSS-induced inflammatory symptoms. Mechanistically, BMAL1 promotes apoptosis by binding to apoptosis-related genes, including Bax, p53, and Bak1, and promotes their expression. Intriguingly, we observe circadian apoptotic rhythms in the homeostatic intestinal epithelium, while Bmal1 deletion reduces cell apoptosis. Consistently, reducing Bmal1 expression by the REV-ERBα agonist SR9009 has the best therapeutic efficacy against DSS-induced colitis at ZT0. Collectively, our data demonstrate that the Bmal1-centered circadian clock is involved in intestinal injury repair.

The mucosal barrier serves as a crucial defense against external pathogens and allergens, being widely distributed across the respiratory, gastrointestinal, urogenital tracts, and oral cavity. Its disruption can lead to various diseases, including inflammatory bowel disease, asthma, urinary tract infections, and oral inflammation. Current mainstream treatments for mucosa-associated diseases primarily involve glucocorticoids and immunosuppressants, but their long-term use may cause adverse effects. Therefore, the development of safer and more effective therapeutic strategies has become a focus of research. Natural products, with their multi-target and multi-system regulatory advantages, offer a promising avenue for the treatment of mucosal diseases. This review summarizes the potential applications of natural products in diseases of mucosal barrier dysfunction through mechanisms such as immune modulation, inflammation inhibition, tight junction protein restoration, and gut microbiota regulation, with the aim of providing insights for the exploration of novel therapeutic strategies.

Inorganic dietary nanoparticles (IDNPs) are frequently utilized as food additives and in packaging, resulting in their exposure becoming a substantial yet often overlooked concern for patients with inflammatory bowel disease (IBD). Considering that impaired intestinal barrier function plays a central role in the pathogenesis of IBD, this review concentrates on the roles and mechanisms of IDNPs in the intestinal barrier (physical, chemical, biological, and immune barriers) of IBD patients. Previous studies have shown that different types of nanoparticles have varying effects on animals in diverse states. In this context, factors such as the source, size, shape, dosage, and duration of action of the nanoparticles, as well as the species, gender, dietary habits, and age of the animals, significantly influence research outcomes. Future studies should undertake more comprehensive explorations into the effects and mechanisms of IDNPs with diverse sources and properties in IBD patients.

Crohn's disease (CD) and ulcerative colitis (UC), referred to as inflammatory bowel disease (IBD), pose considerable challenges in treatment because they are chronic conditions that easily relapse. The occurrence of IBD continues to rise in developing countries. Nonetheless, the existing therapies for IBD have limitations and fail to address the needs of the patients thoroughly. There is an increasing need for new, safe, and highly effective alternative medications for IBD patients. Traditional Chinese Medicine (TCM) is employed in drug development and disease management due to its wide-range of biological activities, minimal toxicity, and limited side effects. Extensive research has shown that certain TCM exhibits significant therapeutic benefits for IBD treatments. Honeysuckle (Lonicera japonica) was used in TCM research and clinical settings for the treatment of IBD. Bioactive metabolites in L. japonica, such as luteolin, quercetin, cyanidin, chlorogenic acid (CGA), caffeic acid (CA), and saponin, exhibit significant therapeutic benefits for managing IBD. The honeysuckle flower is a potential candidate in the treatment of IBD due to its anti-inflammatory, immune system-regulating, and antioxidant qualities. This paper reviews the metabolites of the honeysuckle flower as a candidate for the treatment of IBD. It discusses the fundamental mechanism of L. japonica and the potential of its bioactive metabolites in the prevention and treatment of IBD.

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colorectum, posing a significant global health burden. Recent studies highlight the critical role of gut microbiota and its metabolites, particularly bile acids (BAs), in UC's pathogenesis. The relationship between BAs and gut microbiota is bidirectional: microbiota influence BA composition, while BAs regulate microbiota diversity and activity through receptors like Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Targeting bile-acid metabolism to reshape gut microbiota presents a promising therapeutic strategy for UC. This review examines the classification and synthesis of BAs, their interactions with gut microbiota, and the potential of nutritional and microbial interventions. By focusing on these therapies, we aim to offer innovative approaches for effective UC management.

The activation of inflammasomes (NLRP3 and NLRP1) is central to the pathogenesis of inflammatory bowel disease (IBD). Here we examined the protective effects of a thioredoxin-mimetic peptide CB13 (TXM-CB13), known for its antioxidative stress and anti-inflammatory properties. We examined the effects of TXM-CB13 on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation in RAW264.7 macrophages. TXM-CB13 appeared to alleviate symptoms of DSS-induced colitis and to significantly suppress the protein and mRNA levels of NLRP3, Mlck, and IL-1β in colonic tissues. Additionally, TXM-CB13 treatment increased the levels of the intestinal barrier proteins Occludin, ZO-1, and NLRP1, as shown through immunohistochemistry and Western blot analysis. In vitro, TXM-CB13 inhibited LPS-induced TLR4 signaling, reducing MyD88 levels and consequently attenuating the activation of the NF-κB pathways, including p-IκB-α/IκB-α and p-NF-κB-p65/NF-κB-p65. This inhibition further reduced the activation of the NLRP3 inflammasome components, NLRP3, ASC, Caspase-1, GSDMD, and IL-1β. In addition, TXM-CB13 prevented the ROS-mediated dissociation of TXNIP from TRX, inhibiting NLRP3 activation. These findings suggest that TXM-CB13 is a potential therapeutic candidate for IBD through its modulation of the TLR4/MyD88/NF-κB/NLRP3 and ROS/TXNIP/TRX/NLRP3 pathways.

Background: Reduction of Faecalibacterium prausnitzii abundance is related to inflammatory bowel diseases (IBDs), and supplement of it exists protective effects. Aim: This study aimed to establish a F. prausnitzii-colonized mouse model and investigate that the presence of F. prausnitzii in the gut can ameliorate the severity of dextran sulfate sodium (DSS)-induced colitis. Methods: A F. prausnitzii (ATCC 27768) strain was maintained on the PS-BHI agar plates and manipulated in a strictly anaerobic chamber. A F. prausnitzii-colonized C57BL/6 mice model was tested by a rectal enema with 1 × 109 bacteria/day for 3 days. The 5% DSS was added to drinking water for 3 days to induce colitis and diarrhea in experimental mice. The clinical, cytological, and histological severities were compared between groups. Results: The F. prausnitzii-colonized mice model was successfully established via rectal enema with the property of transfer to offspring. DSS treatment altered gut microbiota and significantly attenuated the abundance of F. prausnitzii in colonized mice. Mice with F. prausnitzii colonization had significantly improved weight loss, anal bleeding, stool consistency, cecum weight, colon length, and serum amyloid A (SAA) level than those without after DSS treatment. Furthermore, the F. prausnitzii-colonized mice significantly reduced the transcription levels of TNF-α, INF-γ and IL-18, and epithelial damage and PMN infiltration in the lamina propria and had better preservation of goblet cells than the control group. Conclusion: We have successfully established a mouse model colonized with F. prausnitzii via rectal enema administration and showed colonization of F. prausnitzii in the gut has a protective effect against DSS-induced colitis.

Epithelial linings are crucial for the maintenance of physiological barriers. The intestinal epithelial barrier (IEB) consists of enterocytes through tight junctions and mucus-secreting cells and can undergo physiological modifications throughout life. To reproduce as closely as possible the IEB main features over time, in vitro co-cultures of Caco2/HT-29 70/30 formed by parental Caco2 and HT-29 cells sub-cultivated for more than 40 passages were set up. The measurements of the transepithelial electrical resistance (TEER) identified two populations: physiological TEER co-cultures (PC) with values > 50 Ωcm2 formed by parental cells with fewer than 40 passages, and leaky TEER co-cultures (LC) with values < 50 Ωcm2 formed by parental cells with more than 40 passages. In LC, paracellular permeability increased in parallel. By immunofluorescence and Western blot analysis, an increase in claudin 2 was observed in LC vs. PC, with no differences in occludin expression. MUC-2 immunoreactivity was stronger in PC than in LC. LC also showed an enhanced vulnerability to TNFα+IFN-γ. These results reproduce the main morpho-functional modifications reported in the human leaky/aged gut and support the usefulness of our in vitro cell model for studying the molecular processes underlying these modifications and testing drug/nutraceutical treatments to ameliorate leaky gut aging.

Theranostic prodrugs that enable real-time, non-invasive monitoring of drug release and biodistribution are highly desirable for optimizing therapeutic efficacy and guiding personalized medication. Herein, we report a colon-targeted theranostic prodrug system (P1) for the simultaneous delivery and tracking of 5-aminosalicylic acid (5-ASA) in the treatment of ulcerative colitis (UC). P1 comprises a fluorescent 7-amino-4-methylcoumarin (7-AMC) reporter covalently linked to 5-ASA via an azo bond, which quenches the fluorescence of 7-AMC until P1 is activated by azoreductases in the colonic microenvironment. This selective activation triggers the release of 5-ASA and the revival of 7-AMC fluorescence, enabling real-time monitoring of drug delivery. To improve the solubility and targeted delivery of P1, it was encapsulated within polymeric micelles (PM) that selectively adhere to the positively charged, inflamed colonic tissues. In vitro studies confirmed the stability, biocompatibility, and selective activation of P1 under simulated colonic conditions. Notably, in a mouse model of UC, the P1-loaded PM achieved targeted delivery of 5-ASA to the inflamed colon, resulting in effective attenuation of colitis symptoms. Importantly, the in situ activation of P1 allowed for the real-time, non-invasive visualization of drug release and biodistribution, providing valuable insights for treatment optimization. This theranostic prodrug approach offers a promising strategy for the simultaneous therapy and tracking of 5-ASA delivery in UC treatment, with the potential to facilitate personalized medication and improve therapeutic outcomes.

Psoriasis is a chronic skin disease occasionally associated with abdominal symptoms and IBD. We aimed to characterize intestinal immune cells and the integrity of the intestinal barrier in psoriasis. Biopsies from the duodenum and colon were analyzed by flow cytometry and immunohistochemistry for the presence and activation status of different immune cell populations. Intestinal permeability was measured using Ussing chambers. Proinflammatory markers were analyzed in fecal and blood samples using ELISA. The intestinal level of inflammatory mediators was assessed using a multiplex proximity extension assay. We found an increased density of intestinal eosinophils, mast cells, macrophages, and CD8+ T-cells in psoriasis; eosinophils, macrophages, and CD8+ T-cells expressed activation markers. Half of the psoriasis patients showed increased permeability across the duodenum, correlating with increased mucosal IL-17A, IL-13, IL-2, and IL-20, and with gastrointestinal symptoms. Our findings reveal that psoriasis is associated with low-grade intestinal inflammation, which may contribute to abdominal symptoms in these patients and possibly set the stage for the development of intestinal disease.

Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.

Background: This study explores the potential of the Pleurotus eryngii mushroom fermentation supernatant (FS-PEWS) as an intervention for mitigating sodium deoxycholate (SDC)-induced intestinal barrier dysfunction and inflammation. Methods: FS-PEWS was assessed for its protective effects against SDC-induced barrier dysfunction and inflammation using an in vitro Caco-2 cell model and ex vivo colonic biopsies from healthy adult donors, where barrier integrity, permeability, immunomodulation and receptor-mediated pathways were evaluated. Results: In Caco-2 cells, SDC exposure downregulated ZO-1, occludin, and claudin-1 expression, with FS-PEWS restoring ZO-1 and claudin-1 levels while maintaining cell viability. In colonic biopsies from healthy adults, FS-PEWS maintained tissue integrity and selectively mitigated transcellular permeability without affecting paracellular permeability when combined with the stressor. Additionally, FS-PEWS exhibited potent anti-inflammatory effects, reducing pro-inflammatory cytokines, e.g., TNF-α, IL-6, and IL-1β and modulating receptor-mediated pathways, i.e., TLR-4, dectin-1. Conclusions: These results demonstrate the potential of FS-PEWS to sustain intestinal barrier function and modulate immune responses under stress, highlighting its therapeutic potential for managing gut barrier dysfunction and inflammation associated with microbial metabolite-induced disruptions.

Zonulin regulates permeability in blood-brain and intestinal barriers. The pathophysiology of migraine is based on the effect of neurogenic inflammation. The aim of the current investigation was to examine the serum zonulin level in individuals suffering from migraine.

The sample comprised 40 individuals who had migraine and 40 controls. Disease duration, attack duration, attack frequency, Visual Analog Scale (VAS) scores, and comorbidities were available for the migraine group. Serum zonulin levels were evaluated by using the ELISA method.

There were no statistically significant differences between the two groups concerning age or gender (p > 0.05). The zonulin value of patients with migraine was higher when compared to the controls, indicating a significant difference (p = 0.037; p < 0.05). The zonulin level did not correlate with disease duration, attack duration, VAS score, or attack frequency (p > 0.05). The receiver operating characteristic curve analysis of zonulin revealed a cut-off value of 30.58 and above, at which it had 52.50% sensitivity, 77.5% specificity, 70% positive predictive value, and 62% a negative predictive value. The area under the curve was 63.6%, and the standard error value was 6.3%. The analysis also showed a statistically significant correlation between migraine diagnosis and a zonulin level of 30.58 (p = 0.006; p < 0.01).

Elevated zonulin levels in patients with migraine support the disruption of the intestinal barrier and neuroinflammation in these patients. The zonulin level may be a predictive biomarker of migraine. Multicenter, randomized trials are needed to evaluate treatments for intestinal permeability and zonulin levels in migraine patients.

Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated with aging. Osteoarthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and cognitive decline associated with dementia are among the most common age-related diseases and contribute significantly to morbidity and mortality in the aged population. Many of these age-related diseases have been linked to chronic low-grade systemic inflammation which often accompanies aging. Gastrointestinal barrier dysfunction, also known as "leaky gut," has been shown to contribute to systemic inflammation in several diseases including inflammatory bowel disease and irritable bowel syndrome, but its role in the development and/or progression of chronic low-grade systemic inflammation during aging is unclear. This review outlines current literature on the leaky gut in aging, how leaky gut might contribute to systemic inflammation, and the links between gastrointestinal inflammatory diseases and common age-related diseases to provide insight into a potential relationship between the intestinal barrier and inflammation.

The intestinal epithelium is a rapidly self-renewing tissue; the rapid turnover prevents the invasion of pathogens and harmful components from the intestinal lumen, preventing inflammation and infectious diseases. Intestinal epithelial barrier function depends on the epithelial cell proliferation and junctions, as well as the state of the immune system in the lamina propria. Polyamines, particularly putrescine, spermidine, and spermine, are essential for many cell functions and play a crucial role in mammalian cellular homeostasis, such as that of cell growth, proliferation, differentiation, and maintenance, through multiple biological processes, including translation, transcription, and autophagy. Although the vital role of polyamines in normal intestinal epithelial cell growth and barrier function has been known since the 1980s, recent studies have provided new insights into this topic at the molecular level, such as eukaryotic initiation factor-5A hypusination and autophagy, with rapid advances in polyamine biology in normal cells using biological technologies. This review summarizes recent advances in our understanding of the role of polyamines in regulating normal, non-cancerous, intestinal epithelial barrier function, with a particular focus on intestinal epithelial renewal, cell junctions, and immune cell differentiation in the lamina propria.

In this study, we investigated the effects of infant fecal fermentation-derived metabolites of digested osteopontin (OPN) and 2'-fucosyllactose (2'-FL), either individually or in combination, on intestinal barrier function using a Caco-2/HT-29 coculture cell model. Our results suggested that the OPN/2'-FL (1:36-1:3) cofermentation metabolites improved epithelial barrier integrity by supporting the mRNA and protein expression of occludin, claudin-1, claudin-2, ZO-1, and ZO-2. All of the OPN/2'-FL treatments decreased the production of IL-1β, IL-6, and TNF-α, while the OPN/2'-FL ratio increased IL-10 production by inhibiting activation of the MyD88/IκB-α/NF-κB signaling pathway. OPN/2'-FL cofermentation altered the metabolic pathways, and the protective effect of fermentation metabolites on intestinal barrier function was related to differential metabolite expression such as short-chain fatty acids, deoxycholic acid, and 4-aminobutyric acid. Our findings provide in vitro evidence to support the application of the OPN/2'-FL combination in infant formula for the advancement of formulation functionality, including intestinal barrier function.

Persistent organic pollutants (POPs) are pervasive organic chemicals with significant environmental and ecological ramifications, extending to adverse human health effects due to their toxicity and persistence. The intestinal mucosal barrier, a sophisticated defense mechanism comprising the epithelial layer, mucosal chemistry, and cellular immunity, shields the host from external threats and fosters a symbiotic relationship with intestinal bacteria. Sirtuin 6 (SIRT6), a sirtuin family member, is pivotal in genome and telomere stability, inflammation regulation, and metabolic processes. Result shows POPs have been implicated in the intestinal diseases, particularly in intestinal barrier dysfunction, through mechanisms such as cellular damage, epigenetic alterations, inflammation, microbiota changes, and metabolic disruptions. While the impact of SIRT6 expression changes on intestinal barrier functions has been reviewed, the mechanisms linking POPs to SIRT6 remain elusive. This review summarized the latest research results on the effects of POPs on intestinal barrier, discussed the role of SIRT6 from multiple mechanism perspectives, proposed new research directions on POPs, SIRT6 and intestinal health, and explored the therapeutic potential of SIRT6.

Amitriptyline, a pleiotropic tricyclic antidepressant, possesses antioxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on inflammatory bowel disease (IBD) are not yet well defined. To explore this, we used a dextran sulfate sodium (DSS)-induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates. Our research revealed that amitriptyline is effective in alleviating several pathological manifestations associated with colitis. This includes improving body weight retention, reducing disease activity index, lessening of colon length shortening, and repairing of colonic mucosal damage. Treatment with amitriptyline significantly protected mucosal injury by preserving the population of goblet cells and increasing the expression of tight junction proteins. Furthermore, we observed that amitriptyline effectively countered immune cell infiltration, specifically neutrophils and macrophages, while simultaneously lowering the levels of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, and IL-6. Additionally, RNA sequencing analysis pointed to the potential involvement of the Toll-like receptor (TLR) pathway in the anticolitic effects induced by amitriptyline. Subsequent Western blot analysis indicated that amitriptyline significantly inhibited the TLR-4-mediated nuclear factor (NF)-κB signaling pathway. To bolster our findings, in vitro studies demonstrated that amitriptyline downregulated the TLR-4/NF-κB/mitogen-activated protein kinase signaling cascades in mouse macrophages stimulated with lipopolysaccharide. Further molecular investigations revealed that amitriptyline was able to suppress the elevated expression of myeloid differentiation factor 2 that lipopolysaccharide stimulation typically induces. In summary, our findings suggest that amitriptyline effectively mitigates DSS-induced colitis in mice through the inhibition of TLR-4/myeloid differentiation 2 pathway signaling, indicating its potential repurposing for IBD treatment. SIGNIFICANCE STATEMENT: The potential of using amitriptyline in treating inflammatory bowel disease appears promising, leveraging its established safety and dosing profile as an antidepressant. The study results show that amitriptyline can alleviate pathological symptoms, inflammation, and intestinal mucosal damage in mice with colitis induced by DSS. The protective effect observed appears to be linked to the inhibition of TLR-4/myeloid differentiation 2 signaling pathway. By exploring novel applications for existing medications, we can optimize amitriptyline's efficacy and broaden its impact in both medical and commercial contexts.

The human intestinal tract plays a pivotal role in safeguarding the body against noxious substances and microbial pathogens by functioning as a barrier. This barrier function is achieved through the combined action of physical, chemical, microbial, and immune components. Tea (Camellia sinensis) is the most widely consumed beverage in the world, and it is consumed and appreciated in a multitude of regions across the globe. Tea can be classified into various categories, including green, white, yellow, oolong, black, and dark teas, based on the specific processing methods employed. In recent times, there has been a notable surge in scientific investigation into the various types of tea. The recent surge in research on tea can be attributed to the plethora of bioactive compounds it contains, including polyphenols, polysaccharides, pigments, and theanine. The processing of different teas affects the active ingredients to varying degrees, resulting in a range of chemical reactions and the formation of different types and quantities of ingredients. The bioactive compounds present in tea are of great importance for the maintenance of the integrity of the intestinal barrier, operating through a variety of mechanisms. This literature review synthesizes scientific studies on the impact of the primary bioactive compounds and different processing methods of tea on the intestinal barrier function. This review places particular emphasis on the exploration of the barrier repair and regulatory effects of these compounds, including the mitigation of damage to different barriers following intestinal diseases. Specifically, the active ingredients in tea can alleviate damage to physical barriers and chemical barriers by regulating barrier protein expression. At the same time, they can also maintain the stability of immune and biological barriers by regulating the expression of inflammatory factors and the metabolism of intestinal flora. This investigation can establish a strong theoretical foundation for the future development of innovative tea products.

(-)-Fenchone is a bicyclic monoterpene present in the plant species Foeniculum vulgare Mill, Thuja occidentalis L. (tuja), and Lavandula stoechas (lavender). These plants have therapeutic value in the treatment of intestinal disorders.

To evaluate intestinal anti-inflammatory activity in an acute and chronic trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats.

Intestinal anti-inflammatory effects were assessed using the acute and chronic TNBS-induced colitis model in rats. The mechanisms were evaluated from colonic tissue fragments of the acute and chronic models.

Oral administration of the (-)-fenchone (37.5-300 mg/kg) acute phase or (150 mg/kg) (p < 0.001) chronic phase reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. At a dose of 150 mg/kg, the acute and chronic phase decreased malondialdehyde (MDA) and myeloperoxidase (MPO) (p < 0.001), restored glutathione (GSH) levels and superoxide dismutase (SOD) (p < 0.001), decreased immunomarking for factor nuclear kappa B (NF-κB) and levels of interleukin (IL)-1 and tumor necrosis factor α (TNF-α), and maintained IL-10 and TGF-β basal levels. Furthermore, increased immunostaining for zonula occludens 1 (ZO-1) was observed.

(-)-fenchone has intestinal anti-inflammatory activity related to cytoprotection of the intestinal barrier, as well as antioxidant and immunomodulatory effects.

Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets and support development. Preterm development is crucial, especially in the maturation of essential systems, and from 2010 to 2020, approximately 15% of all premature births occurred at less than 32 weeks of gestation worldwide. This review explores the composition, benefits, and effects of BC on general infants and children, along with preterm infants who require special care, and highlights its role in growth and development. BC is also associated with specific pediatric diseases, including necrotizing enterocolitis (NEC), infectious diarrhea, inflammatory bowel disease (IBD), short-bowel syndrome (SBS), neonatal sepsis, gastrointestinal and respiratory infections, and some minor conditions. This review also discusses the clinical trials regarding these specific conditions which are occasionally encountered in preterm infants. The anti-inflammatory, antimicrobial, immunomodulatory, and antiviral properties of BC are discussed, emphasizing its mechanisms of action. Clinical trials, particularly in humans, provide evidence supporting the inclusion of BC in formulas and diets, although precise standards for age, feeding time, and amounts are needed to ensure safety and efficacy. However, potential adverse effects, such as allergic reactions to caseins and immunoglobulin E, must be considered. More comprehensive clinical trials are necessary to expand the evidence on BC in infant feeding, and glycans, important components of BC, should be further studied for their synergistic effects on pediatric diseases. Ultimately, BC shows promise for pediatric health and should be incorporated into nutritional supplements with caution.

Ulcerative colitis (UC) is a common inflammatory bowel disease and a risk factor of colorectal cancer. Demethylzeylasteral (DZT), a bioactive component mainly isolated from Tripterygium wilfordii, has been shown to inhibit inflammation and cancer. However, its anti-UC function and molecular mechanisms have not been well characterized. This study aims to explore the therapeutic effect and functional targets of demethylzeylasteral against UC.

RT-qPCR, Western blot and ELISA were used to detect the generation of pro-inflammatory cytokines and chemokines in murine macrophage cells. Luciferase reporter gene, Western blot, pull-down, CETSA, DARTS, and virtual docking were employed to detect the anti-inflammatory targets and molecular mechanisms of demethylzeylasteral. The anti-inflammatory and anti-colitis effects of demethylzeylasteral were further determined in DSS-challenged mice.

In vitro, demethylzeylasteral inhibited NO and PGE2 production by suppressing the mRNA and protein expression of iNOS and COX-2, and suppressed the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1, CXCL9, and CXCL10 in RAW264.7 macrophages stimulated by LPS/IFNγ. Furthermore, demethylzeylasteral was not only capable of inhibiting IKKα/β-NF-κB activation, but also able to block JAKs-STAT3/5 activation in LPS/INFγ-incubated RAW264.7 cells or DSS-exposed colon tissues of mice. Mechanistically, demethylzeylasteral was found to directly bind to IKKα/β and JAK2 kinases, leading to inactivation of pro-inflammatory signaling cascades and reduced generation of cytokines and chemokines. In vivo, oral administration of demethylzeylasteral significantly attenuated DSS-induced colitis, which was mainly manifested as mitigated symptoms of colitis, colonic mucosal barrier damage, and colonic inflammation.

We demonstrated that demethylzeylasteral alleviated UC pathology by blocking NF-κB and STAT3/5 pathways via targeting IKKα/β and JAK2 kinases, raising the possibility that demethylzeylasteral could act as a candidate for the treatment of UC.

Treatments for inflammatory bowel disease (IBD) remain limited, and cannabis-based medicinal products (CBMPs) provide promise in addressing inflammation and pain. However, long-term data on CBMP efficacy in IBD are scarce. This study examines health-related quality of life (HRQoL) changes in IBD patients treated with CBMPs.

Patients with IBD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the short IBD questionnaire (SIBDQ), EQ-5D-5L, single-item sleep quality scale (SQS), and generalized anxiety disorder-7 (GAD-7), from baseline to 18-months after CBMP treatment started. Secondary outcomes were adverse event prevalence.

Analysis of 116 patients with IBD included 94 males (81.03%) with a mean age of 39.52 ± 9.12 years. There were improvements in the SIBDQ, GAD-7, SQS, and EQ-5D-5L Index (p < 0.001). At 18-months, 30 (25.86%) patients achieved a minimal clinically important difference (MCID) in the SIBDQ. Patients with severe baseline anxiety and above-median THC doses were more likely to achieve this MCID (p < 0.050). Twenty (17.24%) patients reported 155 (133.62%) adverse events.

CBMP treatment was associated with improvement in IBD-specific outcomes in patients and general HRQoL over 18-months. However, causation cannot be inferred. Hence, randomized controlled trials are still required.

This study aims to investigate the effects of hesperidin (Hes), thymol (Thy), rosmarinic acid (RA) and their combined effect on broiler growth performance, intestinal barrier function, and cecal microbiota. A total of 240 newly hatched Arbor Acres broiler chicks were randomly divided into 5 treatments with 6 replicates of 8 chickens. The birds were fed a basal diet (Con group), a basal diet supplemented with 40 mg/kg Hes (Hes group), a basal diet supplemented with 40 mg/kg Thy (Thy group), a basal diet supplemented with 20 mg/kg RA (RA group), or a basal diet supplemented with 40 mg/kg Hes + 40 mg/kg Thy + 20 mg/kg RA (HTR group) for 42 d. The results indicated that dietary Hes and HTR supplementation enhanced average daily gain, final body weight, and eviscerated yield of broilers compared with the Con group (P < 0.05). Notably, the HTR treatment showed a decrease in abdominal fat yield and ratio of feed to weight gain (P < 0.05). HTR treatment increased ileal villus height, villus height/crypt depth, and number of goblet cells, decreased the crypt depth (P < 0.05), up-regulated the mRNA expression of tight junction proteins (ZO-1, Claudin-1, Occludin) and MUC2 (P < 0.05). Hes, Thy, RA, HTR treatment decreased the concentrations of pro-inflammatory factors (IL-8, IFN-γ and TNF-α), and down-regulated the mRNA expression of TLR4/MyD88/NF-κB (P < 0.05). Importantly, the supplementation of HTR increased the relative abundance of beneficial bacteria (Parabacteroides, Lachnosiraceae NK4A136 and Turicbacter) and significantly decreased the relative abundance of opportunistic pathogenic bacteria such as Colidextribacter (P < 0.05). Additionally, the concentrations of propionate and butyrate in the cecum were elevated in the HTR group (P < 0.05). These findings indicate that the diet supplemented with HTR improved the growth performance and intestinal barrier function in broilers by modulating the cecal microbiota and its metabolites.

In vitro organoids that mimic the physiological properties of in vivo organs based on three-dimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.

The invasion of luminal antigens and an aberrant immune response resulting from a disrupted physical epithelial barrier are the key characteristics of ulcerative colitis (UC). The restoration of damaged epithelial function is crucial for maintaining mucosal homeostasis and disease quiescence. Current therapies for UC primarily focus on suppressing inflammation. However, most patients fail to respond to therapy or develop secondary resistance over time, emphasizing the need to develop novel therapeutic targets for UC. Our study aimed to identify the potential targets of a novel modified herbal formula from the Zhen Wu Decoction, namely CDD-2103, which has demonstrated promising efficacy in treating chronic colitis.

The effect of CDD-2103 on epithelial barrier function was examined using in vitro and ex vivo models of tissue injury, as well as a chronic colitis C57BL/6 mouse model. Transcriptomic analysis was employed to profile gene expression changes in colonic tissues following treatment with CDD-2103.

Our in vivo experiments demonstrated that CDD-2103 dose-dependently reduced disease severity in mice with chronic colitis. The efficacy of CDD-2103 was mediated by a reduction in goblet cell loss and the enhancement of tight junction protein integrity. Mechanistically, CDD-2103 suppressed epithelial cell apoptosis and tight junction protein breakdown by activating the soluble guanynyl cyclase (sGC)-mediated cyclic guanosine monophosphate (cGMP)/PKG signaling cascade. Molecular docking analysis revealed strong sGC ligand recognition by the CDD-2103-derived molecules, warranting further investigation.

Our study revealed a novel formulation CDD-2103 that restores intestinal barrier function through the activation of sGC-regulated cGMP/PKG signaling. Furthermore, our findings suggest that targeting sGC can be an effective approach for promoting mucosal healing in the management of UC.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.

Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn's disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

Allergic rhinitis (AR) is a widespread allergic condition, with its prevalence continuing to rise globally. This disease has a significant impact on patients' quality of life. Understanding the underlying pathophysiology is important to develop better-targeted therapies. For decades, the primary assumption has been that an allergy is caused by unbalanced and overactive immunological responses against allergens, driven mainly by activated T helper 2 (Th2) cells and due to aberrant T-regulatory cells. The more recent hypothesis that is gaining attention relies on the dysregulation of the epithelial barrier, which might result in allergen uptake as a primary defect in the pathogenesis of allergic reactions. The nasal epithelial barrier is considered a crucial first line of defense in the upper airway, as it protects the host's immune system from exposure to allergens. Thus, this review will discuss AR's epidemiology, predisposing factors, clinical manifestations, laboratory characteristics, and pathogenic mechanisms.

Inflammatory Bowel Disease (IBD) is an enduring inflammatory disease of the gastrointestinal tract (GIT). The complexity of IBD, its profound impact on patient's quality of life, and its burden on healthcare systems necessitate continuing studies to elucidate its etiology, refine care strategies, improve treatment outcomes, and identify potential targets for novel therapeutic interventions. The discovery of a connection between IBD and gut bacterial quorum sensing (QS) molecules has opened exciting opportunities for research into IBD pathophysiology. QS molecules are small chemical messengers synthesized and released by bacteria based on population density. These chemicals are sensed not only by the microbial species but also by host cells and are essential in gut homeostasis. QS molecules are now known to interact with inflammatory pathways, therefore rendering them potential therapeutic targets for IBD management. Given these intriguing developments, the most recent research findings in this area are herein reviewed. First, the global burden of IBD and the disruptions of the gut microbiota and intestinal barrier associated with the disease are assessed. Next, the general QS mechanism and signaling molecules in the gut are discussed. Then, the roles of QS molecules and their connection with IBD are elucidated. Lastly, the review proposes potential QS-based therapeutic targets for IBD, offering insights into the future research trajectory in this field.

Noncommunicable chronic disorders (NCDs) are multifactorial disorders that share a state of chronic, low-grade inflammation together with an imbalance of gut microbiota. NCDs are becoming increasingly prevalent worldwide, and mainly in Western countries, with a significant impact on global health. Societal changes, together with the widespread diffusion of modern agricultural methods and food processing, have led to a significant shift in dietary habits over the past century, with an increased diffusion of the Western diet (WD). WD includes foods high in saturated fat, refined sugars, salt, sweeteners, and low in fiber, and is characterized by overeating, frequent snacking, and a prolonged postprandial state. An increasing body of evidence supports the association between the diffusion of WD and the rising prevalence of NCDs. WD also negatively affects both gut microbiota and the immune system by driving to microbial alterations, gut barrier dysfunction, increased intestinal permeability, and leakage of harmful bacterial metabolites into the bloodstream, with consequent contribution to the development of systemic low-grade inflammation. In this review article we aim to dissect the role of gut microbiota imbalance and gut barrier impairment in mediating the detrimental effects of WD on the development of NCDs, and to identify potential therapeutic strategies.

Inflammatory bowel disease (IBD) is a challenging condition to cure that can occur at any age. The gut microbiome and intestinal epithelial barrier play a crucial role in the development of IBD. 1,3-Dioleoyl-2-palmitoylglycerol (OPO), the predominant triglyceride in breast milk, is a structural lipid with multiple physiological functions. However, the protective effect of OPO on IBD and its underlying mechanism remains unclear. This study showed that oral administration of OPO markedly ameliorated dextran sulfate sodium (DSS)-induced colitis phenotypes. OPO treatment reduced inflammation levels by suppressing the TLR4-MyD88-NF-κB signaling pathway in colitis mice. Furthermore, OPO treatment improved intestinal epithelial barrier function via promoting epithelial cell proliferation and differentiation, inhibiting cell apoptosis, and upregulating tight junction protein expression. The 16S rRNA gene sequencing revealed that OPO treatment restored microbial alpha diversity and reshaped the microbiota of colitis mice. Therefore, our study revealed that OPO exhibited a protective role in DSS-induced colitis via maintaining intestinal epithelial barrier integrity and modulating gut microbiota. Our results highlight that OPO could be used as effective supplements for individuals with IBD or intestinal dysfunctions.

The gastrointestinal tract is one of the main organs affected during systemic inflammation and disrupted gastrointestinal motility is a major clinical manifestation. Many studies have investigated the involvement of neuroimmune interactions in regulating colonic motility during localized colonic inflammation, i.e., colitis. However, little is known about how the enteric nervous system and intestinal macrophages contribute to dysregulated motility during systemic inflammation. Given that systemic inflammation commonly results from the innate immune response against bacterial infection, we mimicked bacterial infection by administering lipopolysaccharide (LPS) to rats and assessed colonic motility using ex vivo video imaging techniques. We utilized the Cx3cr1-Dtr rat model of transient depletion of macrophages to investigate the role of intestinal macrophages in regulating colonic motility during LPS infection. To investigate the role of inhibitory enteric neurotransmission on colonic motility following LPS, we applied the nitric oxide synthase inhibitor, Nω-nitro-L-arginine (NOLA). Our results confirmed an increase in colonic contraction frequency during LPS-induced systemic inflammation. However, neither the depletion of intestinal macrophages, nor the suppression of inhibitory enteric nervous system activity impacted colonic motility disruption during inflammation. This implies that the interplay between the enteric nervous system and intestinal macrophages is nuanced, and complex, and further investigation is needed to clarify their joint roles in colonic motility.

Inflammatory bowel disease (IBD) is characterized by inflammatory conditions in the gastrointestinal tract. According to reports, IBD prevalence is increasing globally, with heavy economic and physical burdens. Current IBD clinical treatment is limited to pharmacological methods; therefore, new strategies are needed. Myeloid-derived growth factor (MYDGF) secreted by bone marrow-derived mononuclear macrophages has beneficial effects in multiple inflammatory diseases. To this end, the present study aimed to establish an experimental IBD mouse model using dextran sulfate sodium in drinking water. MYDGF significantly alleviated DSS-induced colitis, suppressed lymphocyte infiltration, restored epithelial integrity in mice, and decreased apoptosis in the colon tissue. Moreover, the number of M1 macrophages was decreased and that of M2 macrophages was increased by the action of MYDGF. In MYDGF-treated mice, the NF-κB and MAPK pathways were partially inhibited. Our findings indicate that MYDGF could mitigate DSS-induced mice IBD by reducing inflammation and restoring epithelial integrity through regulation of intestinal macrophage polarization via NF-κB and MAPK pathway inhibition. KEY MESSAGES: MYDGF alleviated DSS-induced acute colitis. MYDGF maintains colon epithelial barrier integrity and relieves inflammation. MYDGF regulates colon macrophage polarization. MYDGF partially inhibited the activation of NF-κB and MAPK pathway.