Fermented vegetables, such as fermented cabbage (sauerkraut), have garnered growing interest for their associations with a myriad of health benefits. However, the mechanistic details underlying the outcomes of consuming these foods require further investigation. This study examined the capacity of soluble metabolites in laboratory-scale and commercial-fermented cabbage to protect against disruption of polarized Caco-2 monolayers by interferon gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Laboratory-scale ferments (LSF) were prepared with and without the addition of Lactiplantibacillus plantarum NCIMB8826R (LP8826R) and sampled after 7 and 14 days of incubation. Trans-epithelial electrical resistance (TER) and paracellular permeability to fluorescein isothiocyanate (FITC)-dextran revealed that fermented cabbage, but not raw cabbage or brine, protected against cytokine-induced damage to the Caco-2 monolayers. Barrier-protective effects occurred despite increased IL-8 production following cytokine exposure. Metabolomic analyses performed using gas and liquid chromatography resulted in the identification of 149 and 333 metabolites, respectively. Significant differences were found between raw and fermented cabbage. LSF metabolomes changed over time, and the profiles of LSF with LP8826R best resembled the commercial product. Overall, fermentation resulted in lower carbohydrate and increased lactic acid, lipid, amino acid derivative (including D-phenyl-lactate [D-PLA], indole-3-lactate [ILA], and γ-aminobutyric acid [GABA]), and phenolic compound concentrations. Lactate, D-PLA, and ILA tested individually and combined only partially protected against cytokine-induced TER reductions and increases in paracellular permeability of Caco-2 monolayers. The findings show that intestinal barrier-protective compounds are consistently enriched during cabbage fermentations, irrespective of the scale or microbial additions, which may contribute to the health-promoting potential of these foods.IMPORTANCEFermented vegetables are increasingly associated with health benefits. However, the importance of microbial transformations to foods during the fermentation process remains to be determined. We found that the metabolites in spontaneously fermented cabbage protected polarized intestinal epithelial cells against damage induced by proinflammatory cytokines. Cabbage fermentations resulted in consistent metabolome profiles enriched in bioactive compounds known to be made by beneficial members of the human gut microbiome, including D-phenyl-lactate (D-PLA) and indole-3-lactate (ILA). The metabolomes were distinct from raw cabbage and were further differentiated between commercial and lab ferments, sampling time, and the presence of an exogenous Lactiplantibacillus plantarum strain. Because only partial protection against intestinal barrier disruption was found when individual metabolites (D-PLA, ILA, and lactate) were applied, the findings indicate that the complex mixture of metabolites in a cabbage fermentation offers advantages over single metabolites to benefit intestinal health.

Lactobacillus fermentum has been shown to improve intestinal health and treat colitis; however, its precise efficacy and mechanisms in inflammatory bowel disease remain unclear.

This study aimed to evaluate whether L fermentum and its metabolites, extracellular vesicles, and other components could modulate intestinal barrier function and gut microbiota to alleviate dextran sulfate sodium (DSS)-induced colitis in mice.

Forty-eight mice were randomly assigned to 6 groups: control, DSS, L fermentum+DSS group (LF+DSS), heat-inactivated L fermentum+DSS group (LHF+DSS), L fermentum supernatant solution+DSS group (LSF+DSS), and L fermentum extracellular vesicles+DSS group (LEV+DSS). After a 1-wk acclimation, mice were gavaged daily for 3 wk. Fresh cultures, including live (LF+DSS), heat-inactivated (LHF+DSS), supernatant (LSF+DSS), and extracellular vesicles (LEV+DSS), were prepared daily. During the final 7 d, the control group received normal water, and the other groups received 3% DSS. Data were collected daily, followed by sample collection from the mice.

In this study, significant reductions (P < 0.05) in body weight changes, disease activity index, intestinal damage, and histology scores were observed in the treatment groups, especially LEV+DSS and LF+DSS. Additionally, compared with the DSS group, colonic mucus secretion, as well as claudin-1 and occludin expression, increased significantly (P < 0.05) in the LEV+DSS and LF+DSS groups, whereas proinflammatory cytokines IL-1β and TNF-α decreased (P < 0.05) and IL-10 increased (P < 0.05) in the LEV+DSS group. L fermentum and its components significantly regulated gut microbiota α-diversity and β-diversity, affecting overall composition. Linear discriminant analysis effect size analysis revealed an enrichment of beneficial bacteria including Prevotellaceae_UCG-001, Romboutsia, and Ruminococcus species in the LF+DSS group and Akkermansia, Odoribacter, and Marvinbryantia species in the LEV+DSS group. Both L fermentum and its extracellular vesicles significantly downregulated the gene expression of TNF-α and IL-1β, whereas the expression of IL-10 was upregulated, thereby contributing to the alleviation of colitis symptoms.

This study reveals that L fermentum alleviates colitis through modulation of the gut microbiota and reinforcement of the intestinal mucosal barrier, with its extracellular vesicles potentially playing a key role in this regulatory process.

Macrophages play a crucial role in maintaining intestinal homeostasis and can exhibit either pro-inflammatory M1 or anti-inflammatory M2 phenotypes. The cannabinoid receptor type 2 (CB2) is involved in immune regulation and may represent a therapeutic target in inflammatory bowel disease (IBD). Our study investigates the phenotype of circulating macrophages and CB2 expression in children with IBD, assessing the role of CB2 stimulation in macrophage polarization, iron metabolism, and intestinal barrier function. Macrophages were isolated from 17 children with ulcerative colitis (UC), 21 with Crohn's disease (CD), and 12 healthy controls (CTR). Cells were treated with a CB2 agonist (JWH-133) and an inverse agonist (AM630). CB2 expression and macrophage polarization were assessed by Western blot. Iron metabolism was evaluated through IL-6, hepcidin levels, FPN-1 expression, and iron concentration. Inflammation was assessed by cytokine release. An in vitro "immunocompetent gut" model was used to study the effects of CB2 stimulation on macrophage polarization and intestinal barrier function. CB2 expression was reduced in IBD macrophages. Compared to controls, IBD patients showed increased M1 markers and pro-inflammatory cytokines, with a reduction in M2 markers and IL-13. Altered iron metabolism was observed, with increased [Fe3+], hepcidin release, and DMT1 expression, and reduced FPN-1. CB2 stimulation restored iron metabolism, induced M2 polarization, and improved intestinal barrier function. CB2 could represent a novel therapeutic target for IBD by modulating macrophage function, iron metabolism, and mucosal barrier restoration.

Inflammatory bowel disease (IBD) and colorectal cancer (CRC), as two of the major human intestinal diseases, provide challenges for the medical field. Suppressor of cytokine signaling 3 (SOCS3), a protein molecule that negatively regulates cytokine signaling through multiple pathways, is involved in the regulation of various inflammatory diseases and tumors. In IBD, SOCS3 acts on a variety of cells to repair mucosal damage and balance the immune response, including epithelial cells, macrophages, dendritic cells, neutrophils, and T cells. In CRC, SOCS3 is inextricably linked to tumor cell proliferation, invasion, metastasis, and drug resistance. Therefore, it is crucial to systematically investigate the pathogenic involvement of SOCS3 in IBD and CRC. This article reviews the mechanisms and pathways by which SOCS3 is involved in the inhibition of IBD and the mitigation of CRC, and details the therapeutic options for targeting SOCS3.

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.

Patients with Crohn's disease (CD) exhibit excessive apoptosis of intestinal epithelial cells (IECs), which contributes to damage to the intestinal barrier structure and function, thereby playing a role in the progression of colitis. Preventing IEC apoptosis and protecting the intestinal barrier are critical to alleviating colitis. Natural plant monomers have been reported to possess multiple pharmacological properties, particularly with the potential to treat CD. This study focuses on Cynaroside (Cyn) to explore its effect on IEC apoptosis and evaluate its pharmacological impact on the intestinal barrier and colitis.

The 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis mice model was employed in this study. We assessed the therapeutic effect of Cyn on CD-like colitis by evaluating the disease activity index (DAI), body weight changes, intestinal tissue pathological damage, and inflammatory factor levels. Immunofluorescence and Western blotting were used to detect the expression and localization of tight junction (TJ) proteins, allowing us to analyze the intestinal barrier structure. The function of the intestinal barrier was examined using FITC-dextran (FD4), TEER values, and bacterial translocation. Network pharmacology enrichment analysis revealed that Cyn could inhibit cell apoptosis. We also explored the effect and underlying mechanism of Cyn in inhibiting IEC apoptosis on intestinal barrier function and colitis using both the TNF-α-induced colonic organoid model and the TNBS-induced mouse model.

Our findings show that Cyn significantly alleviates TNBS-induced colitis symptoms in mice, as evidenced by reduced body weight loss, colon shortening, DAI score, colon histopathology score, and lower levels of inflammatory factors (IL-1β, TNF-α, and IL-6) compared to the model group. Additionally, the Cyn intervention group showed significant improvements in both the intestinal barrier structure (elevated tight junction protein levels and proper localization) and function (reduced serum FD4 levels, increased intestinal TEER, and decreased bacterial translocation rates in mesenteric lymph nodes [MLNs] and livers). Combining network pharmacology prediction analysis with our validation data from animal models and colonic organoids, we demonstrated that Cyn significantly inhibits IEC apoptosis, as indicated by a decrease in the proportion of TUNEL-positive cells and changes in apoptosis-related protein levels. KEGG enrichment analysis and signaling pathway intervention experiments confirmed that Cyn inhibits the activation of PI3K/AKT signaling.

Cyn inhibits IEC apoptosis by blocking the PI3K/AKT signaling pathway, which is the primary mechanism underlying its protective effects on the intestinal barrier and its ability to improve CD-like colitis. This study also supports the potential of the Chinese medicine monomer Cyn as a promising therapeutic agent for the treatment of CD.

Noncoding RNAs, particularly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as key players in the pathogenesis and therapeutic strategies for inflammatory bowel disease (IBD). MiRNAs, small endogenous RNA molecules that silence target mRNAs to regulate gene expression, are closely linked to immune responses and inflammatory pathways in IBD. Notably, miR-21, miR-146a, and miR-155 are consistently upregulated in IBD, influencing immune cell modulation, cytokine production, and the intestinal epithelial barrier. These miRNAs serve as biomarkers for disease progression and severity, as well as therapeutic targets for controlling inflammation. This comprehensive review highlights the intricate interplay between the gut microbiota, fecal microbiota transplantation (FMT), and miRNA regulation. It concludes that microbiota and FMT influence miRNA activity, presenting a promising avenue for personalized IBD treatment.

Insoluble dietary fiber (IDF) is a crucial component of cereals, and IDF from cereal bran (IDF-CB) has been reported to have multiple biological activities. However, the effect of IDF-CB on chronic colitis remains underexplored. The study aimed to investigate the impact of IDFs from wheat bran (WBIDF), rice bran (RBIDF), millet bran (MBIDF) and oat bran (OBIDF) on chronic colitis induced by dextran sulfate sodium (DSS). Our findings demonstrated that IDFs-CB supplementation mitigated DSS-induced weight loss and reduced lesions in the colon and spleen. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and oxidative stress markers (MPO, iNOS and MDA)were decreased, and anti-inflammatory cytokine (IL-10) and T-SOD activity were increased after IDF-CB inclusion. Furthermore, IDFs-CB restored intestinal barrier function by regulating gene expression (up-regulated Muc-2, ZO-1 and Occludin, and down-regulated Claudin-1 and Claudin-4). Additionally, we analyzed the gut microbiota and SCFAs composition. WBIDF, MBIDF and OBIDF inhibited the growth of Muribaculaceae_unclassified, Bacteroides and Parasutterella. Conversely, IDFs-CB promoted the growth of Candidatus_Saccharimonas and norank_f__norank_o__Clostridia_UCG-014. Notably, WBIDF enhanced the abundance of Allobaculum, while MBIDF and OBIDF increased the abundance of Lachnospiraceae_NK4A136. Moreover, supplementation with IDFs-CB significantly elevated certain SCFA concentrations-particularly acetic acid and isohexanoic acid. Our results suggested that IDF-CB effectively alleviated DSS-induced chronic colitis; among them，WBIDF exhibited superior efficacy followed by OBIDF，MBIDF，and RBIDF. This study provides a theoretical foundation for dietary recommendations for patients suffering from inflammatory bowel disease.

Psoriasis is a chronic inflammatory autoimmune skin disease characterized by keratinocyte hyperproliferation, primarily driven by the IL-23/IL-17 axis. In addition to immune response, various skin components, including the epidermal barrier and the skin microbiota, have been individually implicated in the disease pathogenesis. Here, we aimed to investigate the interplay between epidermal tight junctions, Staphylococcus aureus enterotoxin B (SEB), and CD4 T cell-mediated immune responses. By immunofluorescence analyses of skin biopsies, we observed that claudin-1 distribution was significantly altered in psoriatic patients, which correlated with the localization of Staphylococcus aureus and SEB across skin layers and with disease severity. Furthermore, functional CD4 TCRvβ17 cells were associated with SEB presence in patients skin and positively correlated with psoriasis severity. Notably, in patients with SEB detected in the dermis, CD4 TCRvβ17 IL-17 cells were linked to barrier abnormalities. Unsupervised analysis stratified psoriasis patients into three groups based on SEB presence and location, supporting the previous findings. The patient group with SEB in the dermis exhibited improved responses to biological therapy, including reductions in PASI score, claudin-1 fragmentation, S. aureus and SEB presence, and CD4 TCRvβ17 cell percentages. Our findings emphasize the complex interplay between epidermal barrier distribution, SEB localization, and functional CD4 TCRvβ17 cells in psoriatic skin, highlighting their potential in patient stratification in association with the severity of the disease.

Subacute ruminal acidosis (SARA) is a common metabolic disease due to feeding high-concentrate (HC) diets to ruminants, especially dairy cows, in intensive farming system. Long term feeding HC diets commonly induce damages to hindgut barrier, leading to the translocation of harmful substances such as endotoxins (LPS) from lumen to blood, which results in a low-grade inflammation and stress response. Secondary bile acids (SBAs) play an important role in maintaining intestinal homeostasis. However, the function of SBAs on the intestinal epithelial barrier in SARA remains unclear. In this study, 15 growing goats were randomly divided into 3 groups, control group (30 % concentrate of dry matter, CON), SARA group (70 % concentrate of dry matter, SARA), and SARA+BAs group (70 % concentrate of dry matte, supplemented with 3 g/d/goat of BAs, SARA+BAs). The changes of mucosal permeability, gut microbiota and bile acids (BAs) profile was measured in the colon. The results showed that compared to CON group, the level of plasma D-lactate and diamine oxidase activity (DAO) (P < 0.05) was elevated in SARA group, while BAs supplementation significantly decreased plasma DAO (P < 0.05). The thickness of colonic mucosa, goblet cells (GCs) number (P < 0.01) and the abundance of MUC2 and occludin expression (P < 0.05) were significantly decreased in SARA group, while BAs supplementation markedly increased GCs number and improved mucosal barrier. BAs effectively reduced the content of LPS and volatile fatty acids (VFAs) in the colonic digesta (P < 0.05). Furthermore, BAs ameliorated SARA-induced reduction of total BAs (P < 0.001), primary BAs (P < 0.05), and conjugated BAs (P < 0.05) including taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA), as well as significantly increased hyodeoxycholic acid (HDCA) and lithocholic acid (LCA) contents in colonic digesta. 16S rRNA gene sequence analysis revealed that BAs decreased the abundance of Prevotella and Treponema, but increased the abundance of Akkermansia which was positively correlated with GCs number and MUC2 abundance. BAs supplementation improved the changes in the abundance of Roseburia, Negativibacillus, Lactobacillus, and unclassified_f_prevotellaceae, which were correlated with TCA, TCDCA, and TDCA levels. RNA-Seq results showed that, compared to SARA group, BAs activated the PPAR signaling pathway which was positively correlated with the number of GCs. In summary, BAs supplementation remodels the profiles of gut microbiota and metabolites, activates the PPAR signaling pathway, and eventually ameliorates intestinal mucosal barrier damage.

Inflammatory bowel disease (IBD) treatment often involves systemic administration of anti-inflammatory drugs or biologics such as anti-TNF-α antibodies. However, current drug therapies suffer from limited efficacy due to unresponsiveness and adverse side effects. To address these challenges, we developed inflammation-targeting nanoparticles (ITNPs) using biopolymers derived from the gum kondagogu (Cochlospermum gossypium) plant. These ITNPs enable selective drug delivery to inflamed regions, offering improved therapeutic outcomes. We designed ITNPs that specifically bind to inflamed regions in both human and mouse intestines, facilitating more effective, uniform, and prolonged drug delivery within the inflamed tissues. Furthermore, we demonstrated that oral administration of ITNPs loaded with urolithin A (UroA), a microbial metabolite or its synthetic analogue UAS03 significantly attenuated chemical- and immune checkpoint inhibitor- induced colitis in pre-clinical models. In conclusion, ITNPs show great promise for delivering UroA or its analogues while enhancing therapeutic efficacy at lower doses and reduced frequency compared to free drug administration. This targeted approach offers a potential solution to enhance IBD treatment while minimizing systemic side effects.

Orally administered nanocarriers play an important role in improving druggability, promoting intestinal absorption, and enhancing therapeutic applications for the treatment of local and systemic diseases. However, the delivering efficiency and cell response in mucosa to orally administered nanocarriers is affected by the physiological environment and barriers in the gastrointestinal tract, the physicochemical properties of the nanocarriers, and their bidirectional interactions. Goblet cells secrete and form extracellular mucus, which hinders the movement of nanoparticles. Meanwhile, intestinal epithelial cells may absorb the NPs, allowing for their transcytosis or degradation. Conversely, nanoparticle-induced toxicity may occur as a biological response to the nanoparticle exposure. Additionally, immune response and cell functions in secretions such as mucin, peptide, and cytokines may also be altered. In this review, we discuss the bidirectional interactions between nanoparticles and cells focusing on enterocytes and goblet cells, M cells, and immune cells in the mucosa according to the essential role of intestinal epithelial cells and their crosstalk with immune cells. Furthermore, we discuss the recent advances of how the physiochemical properties of nanoparticles influence their interplay, delivery, and fate in intestinal mucosa. Understanding the fate of nanoparticles with different physiochemical properties from the perspective of their interaction with cells in mucosa provides essential support for the development, rational design, potency maximation, and application of advanced oral nanocarrier delivery systems.

The incidence of inflammatory bowel disease (IBD), a chronic gastrointestinal disorder, is rapidly increasing worldwide. Unfortunately, the current therapies for IBD are often hindered by premature drug release and undesirable side effects. With the advancement of nanotechnology, the innovative targeted nanotherapeutics are explored to ensure the accurate delivery of drugs to specific sites in the colon, thereby reducing side effects and improving the efficacy of oral administration. The emphasis of this review is to summarize the potential pathogenesis of IBD and highlight recent breakthroughs in carbohydrate-based nanoparticles for IBD treatment, including their construction, release mechanism, potential targeting ability, and their therapeutic efficacy. Specifically, we summarize the latest knowledge regarding environmental-responsive nano-systems and active targeted nanoparticles. The environmental-responsive drug delivery systems crafted with carbohydrates or other biological macromolecules like chitosan and sodium alginate, exhibit a remarkable capacity to enhance the accumulation of therapeutic drugs in the inflamed regions of the digestive tract. Active targeting strategies improve the specificity and accuracy of oral drug delivery to the colon by modifying carbohydrates such as hyaluronic acid and mannose onto nanocarriers. Finally, we discuss the challenges and provide insight into the future perspectives of colon-targeted delivery systems for IBD treatment.

This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.

Purpose: C-reactive protein (CRP) functions as a nonspecific marker in various inflammatory disorders, particularly in evaluating the efficacy of pharmacological treatments in patients with ulcerative colitis. The existing body of evidence does not offer adequate support for the direct implication of CRP in modulating the advancement of ulcerative colitis. Methods: Our study employed a rigorous mouse model. An ulcerative colitis mouse model was established by subjecting CRP-deficient mice to dextran sulfate sodium (DSS) treatment. The phenotype of the mice, which encompassed parameters such as body weight, colon length, and spleen weight, was meticulously evaluated. Additionally, various physiological and biochemical indicators were assessed, including colon histopathology, expression levels of inflammatory factors, and staining of the intestinal mucus layer. Results: The absence of CRP did not significantly affect the phenotype, physiological characteristics, and biochemical indices in a mouse model of ulcerative colitis compared to mice with wild-type CRP. Additionally, eliminating intestinal bacteria flora interference through antibiotic treatment revealed that mice lacking CRP did not demonstrate any notable variations in the ulcerative colitis model. Meanwhile, the survival rate of mice lacking CRP did not exhibit a statistically significant difference compared to wild-type mice. Conclusion: The results of our study suggest that CRP may not directly mediate ulcerative colitis. Instead, it is more likely to be a bystander that is present alongside with elevated inflammatory factors. Further investigation is warranted to determine the precise role of CRP in humans, given the significant limitations associated with the use of mouse models.

Synbiotics, the combination of probiotics and prebiotics, are thought to be a pragmatic approach for the treatment of various diseases, including inflammatory bowel disease (IBD). The synergistic therapeutic effects of probiotics and prebiotics remain underexplored. Clostridium tyrobutyricum, a short-chain fatty acid (SCFA) producer, has been recognized as a promising probiotic candidate that can offer health benefits. In this study, the treatment effects of synbiotics containing C. tyrobutyricum and chitooligosaccharides (COSs) on IBD were evaluated. The results indicated that the synbiotic supplement effectively relieved inflammation and restored intestinal barrier function. Additionally, the synbiotic supplement could contribute to the elimination of reactive oxygen species (ROS) and improve the production of SCFAs through the SCFAs-producer of C. tyrobutyricum. Furthermore, such the synbiotic could also regulate the composition of gut microbiota. These findings underscore the potential of C. tyrobutyricum and COSs as valuable living biotherapeutics for the treatment of intestinal-related diseases.

Inspired by the timely emergence of silkworm pupae from their cocoons, silkworm chrysalis-like probiotic composites (SCPCs) are developed for the comprehensive therapy of inflammatory bowel disease (IBD), in which probiotics are enveloped as the "pupa" in a sequential layering of silk sericin (SS), tannic acid (TA), and polydopamine, akin to the protective "cocoon". Compared to unwrapped probiotics, these composites not only demonstrate exceptional resistance to the harsh gastrointestinal environment and exhibit over 200 times greater intestinal colonization but also safeguard probiotics from the damage of IBD environment while enabling probiotics sustained release. The probiotics, in synergy with SS and TA, provide a multi-crossed comprehensive therapy for IBD that simultaneously addresses various pathological features of IBD, including intestinal barrier disruption, elevated pro-inflammatory cytokines, heightened oxidative stress, and disturbances in the intestinal microbiota. SCPCs exhibit remarkable outcomes, including a 9.7-fold reduction in intestinal permeability, an 8.9-fold decrease in IL-6 levels, and a 2.9-fold reduction in TNF-α levels compared to uncoated probiotics. Furthermore, SCPCs demonstrate an impressive 92.25% reactive oxygen species clearance rate, significantly enhance the richness of beneficial intestinal probiotics, and effectively diminish the abundance of pathogenic bacteria, indicating a substantial improvement in the overall therapeutic effect of IBD.

The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.

Matrine (MT) possesses anti-inflammatory, anti-allergic and antioxidative properties. However, the impact and underlying mechanisms of matrine on colitis are unclear. The purpose of this research was to examine the protective impact and regulatory mechanism of matrine on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. MT alleviated DSS-induced UC by inhibiting weight loss, relieving colon shortening and reducing the disease activity index (DAI). Moreover, DSS-induced intestinal injury and the number of goblet cells were reversed by MT, as were alterations in the expression of zonula occludens-1 (ZO-1) and occludin in colon. Simultaneously, matrine not only effectively restored DSS-induced oxidative stress in colonic tissues but also reduced the production of inflammatory cytokines. Furthermore, MT could treat colitis mice by regulating the regulatory T cell (Treg)/T helper 17 (Th17) cell imbalance. We observed further evidence that MT alleviated the decrease in intestinal flora diversity, reduced the proportion of Firmicutes and Bacteroidetes, decreased the proportion of Proteobacteria and increased the relative abundance of Lactobacillus and Akkermansia in colitis mice. In conclusion, these results suggest that MT may mitigate DSS-induced colitis by enhancing the colon barrier integrity, reducing the Treg/Th17 cell imbalance, inhibiting intestinal inflammation, modulating oxidative stress and regulating the gut microbiota. These findings provide strong evidence for the development and application of MT as a dietary treatment for UC.

Increased apoptosis of intestinal epithelial cells (IECs) is a significant cause of intestinal barrier dysfunction in Crohn's disease (CD). Sophoricoside (SOP) is an isoflavone glycoside known for its anti-apoptotic properties. The aim of this study was to investigate the effects of SOP on mice with CD-like colitis and to understand the underlying mechanisms.

Mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to examine the therapeutic effect of SOP on CD-like colitis and intestinal barrier damage. To further explore SOP's impact on IECs apoptosis and intestinal barrier protection, an in vitro colonic organoid apoptosis model induced by TNF-α was utilized. Network pharmacology was employed to predict the relevant pathways and molecular processes associated with SOP in the treatment of CD.

Treatment with SOP significantly improved colitis symptoms in TNBS mice, as demonstrated by reductions in the Disease Activity Index (DAI), weight loss, colon shortening, macroscopic scores, colonic tissue inflammatory scores, and the expression of pro-inflammatory factors. Our experiments confirmed that SOP protects the intestinal barrier by counteracting IECs apoptosis. Additionally, this study established that SOP reduced IECs apoptosis by inhibiting the PI3K/AKT signaling pathway.

SOP can reduce IECs apoptosis through the inhibition of the PI3K/AKT signaling pathway, thereby protecting the intestinal barrier. This study is the first to illustrate how SOP ameliorates colitis and protects the intestinal barrier, suggesting SOP has potential clinical application in treating CD.

Agarose-derived agaro-oligosaccharides (AgaroS) have been extensively studied in terms of structures and bioactivities; they reportedly possess antioxidant and anti-inflammatory activities that maintain intestinal homeostasis and host health. However, the protective effects of AgaroS on deoxynivalenol (DON)-induced intestinal dysfunction remain unclear. We investigated the effects of AgaroS on DON-induced intestinal dysfunction in mice and explored the underlying protective mechanisms. In total, 32 mice were randomly allocated to four treatments (n = 8 each) for 28 days. From day 1 to day 21, the control (CON) and DON groups received oral phosphate-buffered saline (200 μL per day); the AgaroS and AgaroS + DON groups received 200 mg AgaroS per kg body weight once daily by orogastric gavage. Experimental intestinal injury was induced by adding DON (4.8 mg per kg body weight) via gavage from day 21 to day 28. Phosphate-buffered saline was administered once daily by gavage in the CON and AgaroS groups. Herein, AgaroS supplementation led to a higher final body weight and smaller body weight loss and a lower concentration of plasma inflammatory cytokines, compared with the DON group. The DON group showed a significantly reduced ileal villus height and villus height/crypt depth, compared with the CON and AgaroS + DON groups. However, AgaroS supplementation improved DON-induced intestinal injury in mice. Compared with the DON group, ileal and colonic protein expression levels of claudin, occludin, Ki67, and mucin2 were significantly higher in the AgaroS supplementation group. Colonic levels of the anti-inflammatory cytokine IL-1β tended to be higher in the DON group than in the AgaroS + DON group. AgaroS altered the gut microbiota composition, accompanied by increased production of short-chain fatty acids in mice. In conclusion, our findings highlight a promising anti-mycotoxin approach whereby AgaroS alleviate DON-induced intestinal inflammation by modulating intestinal barrier functional integrity and gut microbiota in mice.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1β, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.

Inter-species microbial transplantations offer the possibility of transferring species-specific microbes and their associated functionality. As a conceptual approach, an intestinal microbiota transplant (IMT) between two marine carnivorous fish species that thrive in different environmental conditions was conducted: from donor Atlantic salmon (Salmo salar) to recipient gilthead seabream (Sparus aurata), after obliterating its basal microbiota with an antibiotic treatment. To confirm that the gut microbiota was able to recover after antibiotics without the influence of the diet, a group of gilthead seabream not submitted to the IMT was kept fasted as an internal control. To assess the effect of the diet after the IMT, two groups of gilthead seabream were respectively fed with their typical diet and with Atlantic salmon diet. At 36 days post-IMT, the gut of the individuals fed with their typical diet was dominated by the feed-associated bacteria, while those fed with the salmon diet had developed a unique microbiota from the convergence of the diet, donor, and recipient microbiota. These results suggested that an intestinal microbiota transplantation may be effective if the basal microbiota from the gut is first cleared and a targeted dietary modification is provided to maintain and enrich the novel bacteria species over time.

Our previous work demonstrated that the anisodamine (ANI) and neostigmine (NEO) combination produced an antiseptic shock effect and rescued acute lethal crush syndrome by activating the α7 nicotinic acetylcholine receptor (α7nAChR). This study documents the therapeutic effect and underlying mechanisms of the ANI/NEO combination in dextran sulfate sodium (DSS)-induced colitis. Treating mice with ANI and NEO at a ratio of 500:1 alleviated the DSS-induced colitis symptoms, reduced body weight loss, improved the disease activity index, enhanced colon length, and alleviated colon inflammation. The combination treatment also enhanced autophagy in the colon of mice with DSS-induced colitis and lipopolysaccharide/DSS-stimulated Caco-2 cells. Besides, the ANI/NEO treatment significantly reduced INF-γ, TNF-α, IL-6, and IL-22 expression in colon tissues and decreased TNF-α, IL-1β, and IL-6 mRNA levels in Caco-2 cells. Meanwhile, the autophagy inhibitor 3-methyladenine and ATG5 siRNA attenuated these effects. Furthermore, 3-methyladenine (3-MA) and the α7nAChR antagonist methyllycaconitine (MLA) weakened the ANI/NEO-induced protection on DSS-induced colitis in mice. Overall, these results indicate that the ANI/NEO combination exerts therapeutic effects through autophagy and α7nAChR in a DSS-induced colitis mouse model.

Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological distress and intestinal microbial changes. Here, we examined whether a 3-month period of Cognitive Behavioral and Mindfulness with Daily Exercise (COBMINDEX) intervention, which improves the wellbeing and inflammatory state of CD patients, may also affect their gut microbiome. Gut microbiota, circulating inflammatory markers and hormones were analyzed in 24 CD patients before (T1) and after 3 months of COBMINDEX (T2), and in 25 age- and sex-matched wait-list control patients at the corresponding time-points. Microbiota analysis examined relative taxonomical abundance, alpha and beta diversity, and microbiome correlations with inflammatory and psychological parameters. At T1, CD patients exhibited a characteristic microbial profile mainly constituted of Proteobacteria (17.71%), Firmicutes (65.56%), Actinobacteria (8.46%) and Bacteroidetes (6.24%). Baseline bacterial abundances showed significant correlations with psychological markers of distress and with IFNγ . Following COBMINDEX, no significant changes in alpha and beta diversity were observed between both study groups, though a trend change in beta diversity was noted. Significant changes occurred in the abundance of phyla, families and genera only among the COBMINDEX group. Furthermore, abundance of phyla, families and genera that were altered following COBMNIDEX, significantly correlated with levels of cytokines and psychological parameters. Our results demonstrated that a short-term intervention of COBMINDEX was associated with changes in microbial indices, some of which are linked to psychological manifestations and systemic inflammation in CD patients. Psychological interventions to reduce chronic stress, such as COBMINDEX, appear to be beneficial in mitigating the pathobiology of CD patients, and may thus provide a useful adjunct to pharmacological therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

It is generally accepted that microbes play a critical role in maintaining gut barrier function, making them ideal to target in order to mitigate the effects of intestinal diseases such as inflammatory bowel disease with specialist supplementations such as probiotic or postbiotic preparations. In this study, specific strains of Lactobacillus helvictus both live and inactivated and Lactobacillus plantarum inactivated were fed to zebrafish at an inclusion level of 6 × 106 cells/g in order to assess the effects on gut barrier function and protection. Taken together, our results indicate that dietary administration of pro- or postbiotics strengthens the gut barrier function and innate immunity of healthy zebrafish in a strain-specific and process-dependent way. With some differences in the response intensity, the three treatments led to increased intestinal villi length and proportion of IELs, reinforcement of the GC population and up-regulated expression of biomarkers of AMP production and tight junction zona-occludin 2a (zo-2a). In addition, LPPost had an impact on the adaptive immune response, and we hypothesized that it conferred the potential to drive Th17/ILC3 immunity, as suggested by its effect on the gene expression of il22, of different AMPs, and the expression of zo2a. Moreover, LPPost showed the potential to drive Th1/ILC1-like immunity, with a higher percentage of CD8+ cells and higher ifnγ gene expression. In summary, the use of inactivated Lactobacilli species in this study represented a promising strategy for improving barrier function and regulating the immune fate of the intestinal mucosa in a strain-specific way.

The enteric nervous system is an autonomous neuronal circuit that regulates many processes far beyond the peristalsis in the gastro-intestinal tract. This circuit, consisting of enteric neurons and enteric glial cells, can engage in many intercellular interactions shaping the homeostatic microenvironment in the gut. Perhaps the most well documented interactions taking place, are the intestinal neuro-immune interactions which are essential for the fine-tuning of oral tolerance. In the context of intestinal disease, compelling evidence demonstrates both protective and detrimental roles for this bidirectional neuro-immune signaling. This review discusses the different immune cell types that are recognized to engage in neuronal crosstalk during intestinal health and disease. Highlighting the molecular pathways involved in the neuro-immune interactions might inspire novel strategies to target intestinal disease.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

Acute pancreatitis (AP) is one of the most common acute abdominal conditions, and its incidence has been increasing for years. Approximately 15-20% of patients develop severe AP (SAP), which is complicated by critical inflammatory injury and intestinal dysfunction. AP-associated inflammation can lead to the gut barrier and function damage, causing dysbacteriosis and facilitating intestinal microbiota migration. Pancreatic exocrine deficiency and decreased levels of antimicrobial peptides in AP can also lead to abnormal growth of intestinal bacteria. Meanwhile, intestinal microbiota migration influences the pancreatic microenvironment and affects the severity of AP, which, in turn, exacerbates the systemic inflammatory response. Thus, the interaction between the gut microbiota (GM) and the inflammatory response may be a key pathogenic feature of SAP. Treating either of these factors or breaking their interaction may offer some benefits for SAP treatment. In this review, we discuss the mechanisms of interaction of the GM and inflammation in AP and factors that can deteriorate or even cure both, including some traditional Chinese medicine treatments, to provide new methods for studying AP pathogenesis and developing therapies.

Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the "epithelial barrier hypothesis". Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to dysbiotic bacteria. Here, we provide scientific evidence on the altered human exposome and its impact on epithelial barriers.

Barrier surfaces composed of specialized epithelial cells separate the host body from the external environment, and are essential for maintaining proper intestinal physiologic and immune homeostasis.

To explore the development trends and research hotspots of intestinal barrier research in inflammatory bowel disease (IBD).

The publications related to the intestinal barrier in IBD were obtained from the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace and R software.

A total of 4482 articles published between 2002 and 2022 were identified. The United States is dominant in intestinal barrier research, whereas the University of Chicago is the most active institution. Jerrold from Harvard Medical School was the most productive authors with the most citations. The journals Inflammatory Bowel Disease and Gastroenterology have made significant contributions in this field. The keywords appearing at high frequency related to the intestinal barrier in IBD were detected, including nuclear factor kappa B, tumor necrosis factor-α, apoptosis, oxidative stress and probiotics. Among them, antioxidants, Akkermansia muciniphila, nanoparticles, short-chain fatty acids and extracellular vesicles have received growing interest in recent research.

The intestinal barrier field is developing rapidly with extensive cooperation. Targeting the gut microbiota and dietary metabolism to regulate the intestinal barrier has shown promising prospective applications and has generated broad interest. The importance of the intestinal barrier in IBD is gradually being fully recognized, providing a new therapeutic perspective for improving inflammation and prognosis.

Inflammatory bowel disease (IBD) is typically managed using medications such as 5-aminosalicylic acid (5-ASA), glucocorticoids, anti-TNFα Ab, or anti-IL-12/23 Ab. However, some patients do not respond well to these treatments or frequently experience relapses. Therefore, alternative therapeutic options are needed. Since the activation of the inflammasome is crucial to the pathogenesis of IBD, inhibiting the inflammasome may be beneficial for patients.

We tested the efficacy of taurodeoxycholate (TDCA), which is a known G-protein coupled receptor 19 (GPCR19) agonist, in a mouse colitis model induced by dextran sodium sulfate (DSS).

In the mouse colitis model, TDCA prevented loss of body weight, shortening of the colon, production of pro-inflammatory cytokines, infiltration of pro-inflammatory cells, and mucosal ulceration in the colon. In vitro, TDCA inhibited the activation of NF-κB in bone marrow-derived macrophages (BMDMs) by activating the cAMP-PKA axis. TDCA downregulated the expression of purinergic receptor P2X7 (P2X7R) and enhanced the colocalization of P2X7R with GPCR19, and inhibited the Ca2+ mobilization of BMDMs when stimulated with ATP or BzATP, which plays a pivotal role in activating the NLRP3 inflammasome (N3I) via P2X7R. TDCA inhibited the oligomerization of NLRP3-ASC and downregulated the expression of NLRP3 and ASC, as well as suppressed the maturation of pro-caspase-1 and pro-IL-1β. TDCA also increased the percentage of M2 macrophages while decreasing the number of M1 macrophages, Th1, Th2, and Th17 cells in the colon.

TDCA ameliorated DSS-induced colitis in mice, possibly by inhibiting both the priming phase (via the GPCR19-cAMP-PKA-NF-κB axis) and the activation phase (via the GPCR19-P2X7R-NLRP3-Caspase 1-IL-1β axis) of N3I signaling.

Omentin-1 production is decreased in patients with IBD. However, the specific role of Omentin-1 in IBD has not been fully elucidated. This study aimed to investigate the expression and role of Omentin-1 in IBD and the potential mechanisms.

We collected human serum and colon biopsy samples at the Wuhan Union Hospital. Omentin-1 recombinant protein was injected intraperitoneally in a DSS-induced experimental IBD mouse model. Omentin-1 levels were measured in IBD patients, colitis mice, and LPS-induced HT-29 cells. Omentin-1 and/or a Nrf2 specific inhibitor (ML385) were administered to DSS mice and LPS-induced HT-29 cells. The effects of Omentin-1 on inflammation, intestinal barrier function, Nrf2 pathway, oxidative stress, and NF-κB signaling were detected in vivo and in vitro.

Serum Omentin-1 levels were significantly reduced in UC and CD patients compared with controls (173.7 (IQR, 120.1-221.2) ng/ml, 80.8 (43.8-151.8) ng/ml, and 270.7 (220.7-306.5) ng/ml, respectively). The levels of Omentin-1 were also significantly lower in colitis mice and LPS-induced HT-29 cells. Omentin-1 treatment effectively ameliorated inflammation and impaired intestinal barrier, decreased ROS and MDA levels, and increased GSH and SOD production in the DSS-induced colitis mice and LPS-induced HT-29 cells. Mechanically, Omentin-1 repaired the intestinal barrier by activating Nrf2, then improving oxidative stress and inhibiting NF-κB signaling. Furthermore, the interaction between Omentin-1 and Nrf2 was identified.

Omentin-1 activates the Nrf2 pathway to regulate redox balance, ultimately protecting intestinal barrier function and reducing intestinal inflammation. In general, Omentin-1 can be used as a promising therapeutic target for IBD.

Non-coding RNAs (ncRNA) have paved the way to new perspectives on the regulation of gene expression, not only in biology and medicine, but also in associated fields and technologies, ensuring advances in diagnostic means and therapeutic modalities. Critical in this multistep approach are the associations of long non-coding RNA (lncRNA) with diseases and their causal genes in their networks of interactions, gene enrichment and expression analysis, associated pathways, the monitoring of the involved genes and their functional roles during disease progression from one stage to another. Studies have shown that Johne's Disease (JD), caused by Mycobacterium avium subspecies partuberculosis (MAP), shares common lncRNAs, clinical findings, and other molecular entities with Crohn's Disease (CD). This has been a subject of vigorous investigation owing to the zoonotic nature of this condition, although results are still inconclusive. In this review, on one hand, the current knowledge of lncRNAs in cells is presented, focusing on the pathogenesis of gastrointestinal-related pathologies and MAP-related infections and, on the other hand, we attempt to dissect the associated genes and pathways involved. Furthermore, the recently characterized and novel lncRNAs share common pathologies with IBD and JD, including the expression, molecular networks, and dataset analysis results. These are also presented in an attempt to identify potential biomarkers pertinent to cattle and human disease phenotypes.

The latest guideline about ulcerative colitis (UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall (mechanical barrier) injury with the imbalance between intestinal epithelial cells (IECs) regeneration and death, as well as tight junction (TJ) dysfunction. It is suggested that biological barrier (gut microbiota), chemical barrier (mucus protein layer, MUC) and immune barrier (immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This study aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.