Inflammatory Bowel Research Articles

Advances in research on the role of high carbohydrate diet in the process of inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD) is a chronic, systemic gastrointestinal disorder characterized by episodic inflammation that requires life-long management. Although the etiology of IBD is not fully understood, it is hypothesized to involve a multifaceted interplay among genetic susceptibility, the host immune response, and environmental factors. Previous studies have largely concluded that IBD is associated with this complex interplay; however, more recent evidence underscores the significant role of dietary habits as risk factors for the development of IBD. In this review, we review the molecular mechanisms of high-sugar and high-fat diets in the progression of IBD and specifically address the impacts of these diets on the gut microbiome, immune system regulation, and integrity of the intestinal barrier, thereby highlighting their roles in the pathogenesis and exacerbation of IBD.

The holistic management of peripheral spondyloarthritis: focus on articular involvement in patients with inflammatory bowel disease.

To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD). An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding. pSpA is the most common extraintestinal manifestation in IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several "red flags" guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed. Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model.

Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD.

Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn's Disease.

Crohn's disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived enzyme that produces hypochlorous acid, as a marker of disease activity in children with CD. This observational study assessed myeloperoxidase (MPO) levels in fecal samples from children aged <17 years with CD (51 with active or 42 inactive disease) measured by enzyme-linked immunosorbent assay (ELISA) and compared to controls (35 healthy siblings and 15 unrelated well children). Results were correlated with fecal calprotectin, serum C-reactive protein, urinary glutathione sulfonamide (a biomarker of hypochlorous acid), and disease activity scores. Differences between groups were assessed by analysis of variance. Receiver-operating-characteristic curves were used to assess how biomarkers predicted disease and disease activity. Fecal myeloperoxidase activity and fMPO protein correlated with fecal calprotectin (r = 0.78, P < .0001, and r = 0.81, P < .0001, respectively). Fecal myeloperoxidase activity and protein levels were significantly higher (P ≤ .0001) in individuals with active disease compared to healthy sibling controls, unrelated well children, and those with inactive disease. A 9.7 µg/g fMPO protein cutoff distinguished inactive from active disease (sensitivity = 75%, specificity = 76%). Urinary GSA was elevated in children with active disease (P < .0001) and correlated with fMPO protein (r = 0.43, P = .0002) in a subset of 72 children with IBD and controls. Fecal myeloperoxidase may be superior to fCal at reflecting disease severity in children with CD and produces the damaging oxidant hypochlorous acid during active inflammation.

Unique quantitative electroencephalography differences and related behavioral dynamics in Crohn’s disease

Crohn's disease (CD) is a major type of inflammatory bowel disease (IBD) characterized by idiopathic, chronic inflammation with a patchy transmural inflammatory pattern. CD patients experience a decreased quality of life due to symptoms such as diarrhea, abdominal pain, anemia and fever. This study had a cross-sectional single-center design. The experimental group was composed of patients diagnosed with CD according to the Chinese consensus on diagnosis and treatment in inflammatory bowel disease (2018, Beijing). Fifty CD patients and 41 healthy controls were involved in this study and underwent quantitative electroencephalography (QEEG). Analysis showed that the LZC of QEEG in electrode positions O1, O2 and P4 was lower in the CD group than in the control group. Significant differences in EEG LZC were found at electrode positions F4 and P3 when comparing CD patients with a disease duration of over 10 years to those with a duration of less than 10 years. In CD, the connections between the occipital region and other brain regions may be reduced, and the dynamic behaviors may be simplified. With greater durations of CD, patients may gradually develop simplification of behavioral dynamics in particular brain regions.

Fatigue in patients with inflammatory bowel disease in remission one year after diagnosis (the IBSEN III study).

Fatigue is commonly observed in Crohn's disease (CD) and ulcerative colitis (UC), but its association to achieving remission is not clearly established. In this study we describe the odds for fatigue in patients with CD/UC one year after diagnosis based on different definitions of remission and identified factors associated with chronic fatigue (CF) among patients in endoscopic/radiological remission. Patients ≥18 years with CD/UC were recruited from the IBSEN III cohort. Using the Fatigue Questionnaire, and dichotomizing the score, CF was defined as the presence of substantial fatigue (SF) for ≥6 months. Remission was divided into symptomatic (CD: HBI score<5/UC: SCCAI score<3), biochemical (faecal calprotectin ≤250µg/g), endoscopic/radiological (CD: normal intestinal MRI/CT combined with normal endoscopy/UC: Mayo endoscopic score 0) and histological (normal mucosal biopsies). Both the likelihood of SF/CF, depending on the definition of remission, and associations between CF and selected factors for CD/UC in endoscopic/radiological remission, were evaluated using binary logistic regression analysis. In total, 711/1416 patients were included. For both CD and UC, symptomatic remission significantly reduced the odds for SF and CF. Additionally, the odds for SF were significantly reduced for UC in biochemical remission. Among those in endoscopic/radiological remission (n=181), CF was independently associated with sleep disturbances (OR=10.40, 95%CI [3.28;32.99], p<0.001) and current treatment with infliximab (OR=4.31, 95%CI [1.15;16.17], p=0.03). Stricter definitions of disease remission were not associated with a decreased likelihood of fatigue. For patients in endoscopic/radiological remission, CF was independently associated with sleep disturbances and current treatment with infliximab.

METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis.

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-κB pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-α. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-α-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC.

Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits.

Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated in these phenotypes. Combining CSF and brain, we identified 71 metabolite-trait associations, such as glycerophosphocholines with Alzheimer's disease, O-sulfo-L-tyrosine with Parkinson's disease, glycine, xanthine with waist-to-hip ratio and ergothioneine with inflammatory bowel disease. Our study expanded the knowledge of MQTLs in the central nervous system, providing insights into human traits.

Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.

Integrin heterodimers containing an Integrin alpha V subunit are essential for development and play critical roles in cell adhesion and signaling. We identified biallelic variants in the gene coding for Integrin alpha V (ITGAV) in three independent families (two patients and four fetuses) that either caused abnormal mRNA and the loss of functional protein or caused mistargeting of the integrin. This led to eye and brain abnormalities, inflammatory bowel disease, immune dysregulation, and other developmental issues. Mechanistically, the reduction of functional Integrin αV resulted in the dysregulation of several pathways including TGF-β-dependent signaling and αVβ3-regulated immune signaling. These effects were confirmed using immunostaining, RNA sequencing, and functional studies in patient-derived cells. The genetic deletion of itgav in zebrafish recapitulated patient phenotypes including retinal and brain defects and the loss of microglia in early development as well as colitis in juvenile zebrafish with reduced SMAD3 expression and transcriptional regulation. Taken together, the ITGAV variants identified in this report caused a previously unknown human disease characterized by brain and developmental defects in the case of complete loss-of-function and atopy, neurodevelopmental defects, and colitis in cases of incomplete loss-of-function.

Vancomycin may be an effective attempt in primary sclerosing cholangitis: antibiotic or immunomodulator

Primary Sclerosing Cholangitis(PSC) is a rare, chronic liver disease characterized by bile duct inflammation and concentric fibrogenesis. To date, there has been no evidence that any drug therapy can alter the natural course of this disease. PSC is often concomitant with inflammatory bowel disease(IBD), but the pathogenesis remains unclear. Oral antibiotics have been shown to improve PSC and concomitant IBD, and vancomycin is the most widely used. Therefore, this paper reviews literatures on the application of vancomycin in PSC, aiming to explore therapeutic approaches for PSC that target other pathophysiological pathways.

Assessment of Biofilm Formation and Anti-Inflammatory Response of a Probiotic Blend in a Cultured Canine Cell Model

Gut dysbiosis and an inflamed bowel are growing concerns in mammals, including dogs. Probiotic supplements have been used to restore the natural microbial community and improve gastrointestinal health. Biofilm formation, antimicrobial activities, and immunological responses of probiotics are crucial to improving gut health. Thus, we tested a commercial probiotic blend (LabMAX-3), a canine kibble additive comprising Lactobacillus acidophilus, Lacticaseibacillus casei, and Enterococcus faecium for their ability to inactivate common enteric pathogens; their ability to form biofilms; epithelial cell adhesion; and their anti-inflammatory response in the Madin-Darby Canine Kidney (MDCK) cell line. Probiotic LabMAX-3 blend or individual isolates showed a strong inhibitory effect against Salmonella enterica, Listeria monocytogenes, enterotoxigenic Escherichia coli, and Campylobacter jejuni. LabMAX-3 formed biofilms comparable to Staphylococcus aureus. LabMAX-3 adhesion to the MDCK cell line (with or without lipopolysaccharide (LPS) pretreatment) showed comparable adhesion and biofilm formation (p &lt; 0.05) to L. casei ATCC 334 used as a control. LabMAX-3 had no cytotoxic effects on the MDCK cell line during 1 h exposure. The interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFα) ratio of LabMAX-3, compared to the L. casei control, showed a significant increase (p &lt; 0.05), indicating a more pronounced anti-inflammatory response. The data show that LabMAX-3, a canine kibble supplement, can improve gastrointestinal health.

Drug Interaction-Informed Approaches to Inflammatory Bowel Disease Management

Inflammatory bowel disease (IBD) is a complex and chronic condition that requires the use of various pharmacological agents for its management. Despite advancements in IBD research, the multifaceted mechanisms involved continue to pose significant challenges for strategic prevention. Therefore, it is crucial to prioritize safe and effective treatment strategies using the currently available pharmacological agents. Given that patients with IBD often require multiple medications due to combination therapy or other underlying conditions, a comprehensive understanding of drug interactions is essential for optimizing treatment regimens. In this review, we examined the pharmacological treatment options recommended in the current IBD management guidelines and provided a comprehensive analysis of the known pharmacokinetic interactions associated with these medications. In particular, this review includes recent research results for the impact of anti-drug antibodies (ADAs) on the concentrations of biological agents used in IBD treatment. By leveraging detailed interaction data and employing personalized dosing strategies, healthcare providers can improve therapeutic outcomes and minimize adverse effects, ultimately improving the quality of care for patients with IBD.

The cellular-differential composition of the intestinal epithelium in various phases of inflammatory bowel diseases

BACKGROUND: The steady increase in the number of inflammatory bowel diseases and the absence of reliably significant diagnostic markers require the search for new morphological criteria for differential diagnosis. AIM: This study aimed to determine the cellular-differential composition of the intestinal epithelium in the phases of exacerbation and remission in Crohn’s disease and ulcerative colitis. MATERIALS AND METHODS: Tissue samples of 60 patients with inflammatory bowel diseases (Crohn’s disease, n=30; ulcerative colitis, n=30) and with irritable bowel syndrome (control group, n=15) were studied using histological, immunohistochemical, morphometric and statistical methods. RESULTS: Distinct features of the cellular-differential composition of the epithelium in the mucous membrane of the ileum, ascending colon, sigmoid colon, and rectum were identified across these conditions, with differences observed during exacerbation and remission in inflammatory bowel diseases. The proportion of goblet cells in the epithelial lining varied by intestinal region and disease type and phase. Goblet cell differentiation: 25.0% more goblet cells of the superficial epithelium between the crypts of the ileum in acute Crohn’s disease compared with remission (p=0.0002); 42.9% more goblet cells in the superficial epithelium of the ascending colon compared with irritable bowel syndrome (p=0.0001); 23.0% more goblet cells crypt in the sigmoid colon compared with ulcerative colitis in the acute stage (p=0.0024). There were no significant differences in the differentiation of Paneth cells. There was a threefold increase in endocrinocytes in the sigmoid colon in acute Crohn’s disease compared with irritable bowel syndrome (p=0.0238). Nonepithelial differon cells: fewer interepithelial lymphocytes in Crohn’s disease in remission compared with Crohn’s disease in the acute stage by 2.4 times in the sigmoid colon, 4.0 times in the rectum (p 0,0001); compared with irritable bowel syndrome by 4.8 times in the ileum, 2.7 times in the ascending intestine, 4.0 times in the sigmoid colon (p 0,05); 8.0 times in the rectum compared with ulcerative colitis in remission (p=0,0004). Additionally, the study found proliferative activity of crypt cells (mainly goblet-shaped) increased by 4.2 times in the sigmoid colon in acute Crohn’s disease compared with acute ulcerative colitis (p=0,0016). CONCLUSIONS: Morphometric parameters of the cellular-differential composition of the intestinal epithelium can serve as potential differential diagnostic criteria. Acute Crohn’s disease is characterized by a higher proliferation index in the sigmoid colon compared with acute ulcerative colitis, while Crohn’s disease in remission shows a lower number of interepithelial lymphocytes in the rectum compared with ulcerative colitis in remission.

Infusion Reactions to Infliximab in Pediatric Patients with Inflammatory Bowel Disease

Infliximab (IFX) is a recombinant DNA-derived chimeric IgG monoclonal antibody protein that inhibits tumor necrosis factor alpha (TNF-α). IFX, like other agents derived from foreign proteins, can cause infusion reactions both during and after the infusion. The incidence of infusion reactions ranges between 0% and 15% in pediatric patients. The potential underlying mechanisms for these reactions may include anaphylaxis and anaphylactoid reactions, cytokine release syndrome, serum sickness-like reactions, and the development of antibodies against IFX. Several precautions can help reduce the risk of a new infusion reaction, such as a gradual increase in the infusion rate, scheduled infusions, and administering premedication or immunomodulators alongside IFX. Acute mild to moderate reactions often resolve spontaneously after a temporary cessation of the infusion or reduction in the infusion rate. Strategies like graded dose challenges and premedication can be utilized to prevent recurrence. In cases of severe reactions, desensitization or switching to an alternative biologic may be considered. This article aims to review the most recent guidelines for managing IFX-related infusion reactions in pediatric patients with inflammatory bowel disease (IBD), relying on the best available evidence.

Perspectives on the sustained engagement with digital health tools: protocol for a qualitative interview study among people living with Inflammatory Bowel Disease or irritable bowel syndrome

IntroductionDigital health tools can be beneficial in the care of patients with chronic conditions and have the potential for widespread impact as readily scalable and cost-effective health interventions. However, benefits...

Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway.

While studies have shown that Angelica gigas Nakai (A. gigas) can alleviate ulcerative colitis in mice, the therapeutic role of its main active ingredient, decursin, is uncertain. Therefore, we aimed to investigate the protective effect and mechanism of decursin against inflammatory bowel disease (IBD) in vivo using mice. IBD was simulated via induction with 3% dextran sodium sulfate (DSS), with or without daily treatment with decursin (10 mg/kg or 20 mg/kg) or 5-amino salicylic acid (5-ASA; 100 mg/kg) for 14 days. Mice were weighed and monitored daily for disease activity index (DAI) scoring. Colon tissues were collected for histopathological staining analysis, and serum was collected for ELISA measurement of proinflammatory cytokines. Western blotting was employed to analyze colonic expression levels of the tight junction-related proteins ZO-1, Occludin, and Claudin 1, as well as cGAS-STING signaling pathway-associated proteins. The expression levels of major proteins were verified using immunohistochemistry and immunofluorescence. Compared with the control group, DSS-induced mice showed decreased body weight, increased DAI scores, shortening of the colon, disrupted colon tissue structure, increased serum levels of proinflammatory cytokines, increased expression of factors involved in activating the cGAS-STING signaling pathway, and reduced expression of ZO-1, Occludin, and Claudin 1. Under decursin treatment, the pathological state of IBD was less severe, proinflammatory factors were downregulated, and activation of the cGAS-STING signaling pathway was inhibited. Our findings indicate that decursin helps restore the intestinal mucosal barrier and prevents activation of the cGAS-STING signaling cascade, alleviating experimental IBD in mice.

Effects of an anti-inflammatory diet (AID) on maternal and neonatal health outcomes in pregnant Chinese patients with inflammatory bowel disease treated with infliximab (IFX)

Objective This study aimed to evaluate the effects of an anti-inflammatory diet (AID) combined with Infliximab (IFX) therapy on maternal and neonatal health outcomes in pregnant Chinese patients with inflammatory bowel disease (IBD). Methods IBD patients treated with steady IFX maintenance therapy at the time of conception were randomly assigned to either the IBD-AID group (n = 49), which received an anti-inflammatory diet intervention during the third trimester, or the habitual diet group (n = 49). Primary outcomes included assessments of disease activity, inflammatory markers, and neonatal health. Secondary outcomes included health-related quality of life (HRQoL) in patients and functional gastrointestinal disorders (FGIDs) in infants. Results The IBD-AID intervention significantly reduced disease activity scores in IBD patients at 4 weeks post-intervention and 1 month postpartum compared to the habitual diet group, and also improved HRQoL. Serum C-reactive protein (CRP) and fecal calprotectin (FC) levels were significantly lower in the IBD-AID group at these times, with a trend towards lower levels at 6 months postpartum. Birth weight and Apgar scores were higher in the IBD-AID group but did not reach statistical significance. The incidence of at least one FGID in infants was significantly lower in the IBD-AID group (24.5%) compared to the habitual diet group (46.9%, p = 0.034). Conclusion The IBD-AID intervention combined with IFX therapy significantly improved disease activity, inflammatory markers, and QoL in maternal IBD patients, and was associated with a lower incidence of FGIDs in infants, indicating benefits for both maternal and neonatal health.

Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model

A novel lipid nanoparticle (nLNP), formulated with three essential lipids to mimic ginger-derived exosomal particles, shows strong potential for delivering IL-22 mRNA specifically to the colon, presenting a unique oral drug delivery system for inflammatory bowel disease (IBD). However, its cellular targets and uptake behavior in healthy versus diseased colons remain unclear. Understanding these aspects is crucial for fully elucidating its targeting effectiveness in inflamed colon tissue. This study investigates the nLNP’s cellular targets in healthy and diseased mouse colons. Flow cytometry compared nLNP uptake in healthy mice and a DSS-induced acute colitis model. The results revealed efficient internalization of nLNP by colonic epithelial cells in healthy and inflamed mice. In non-inflamed mice, the small number of colonic macrophages resulted in minimal uptake of nLNP by these cells. In inflamed mice, macrophages migrated to the damaged epithelium, where nLNP uptake was significantly increased, highlighting the nLNP’s ability to target both epithelial and macrophage cells during inflammation. Additionally, safety assessments showed that the nLNP neither altered in vitro kinase activities nor exhibited immunotoxicity or induced in vivo toxicity at the maximum tolerated oral dose. These findings underscore the nLNP’s safety and potential as a promising epithelial/macrophage-targeted drug delivery platform for oral ulcerative colitis (UC) treatment.

Mesenchymal stem cells: a novel therapeutic approach for feline inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action.MethodsWe conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis.ResultsAccording to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways.ConclusionThe collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations.

Identifying Common Genetic Etiologies Between Inflammatory Bowel Disease and Related Immune-Mediated Diseases

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of developing immune-mediated diseases. However, the genetic basis of IBD is complex, and an integrated approach should be used to elucidate the complex genetic relationship between IBD and immune-mediated diseases. Methods: The genetic relationship between IBD and 16 immune-mediated diseases was examined using linkage disequilibrium score regression. GWAS data were synthesized from two IBD databases using the METAL, and multi-trait analysis of genome-wide association studies was performed to enhance statistical robustness and identify novel genetic associations. Independent risk loci were meticulously examined using conditional and joint genome-wide multi-trait analysis, multi-marker analysis of genomic annotation, and functional mapping and annotation of significant genetic loci, integrating the information of quantitative trait loci and different methodologies to identify risk-related genes and proteins. Results: The results revealed four immune-mediated diseases (AS, psoriasis, iridocyclitis, and PsA) with a significant relationship with IBD. The multi-trait analysis revealed 909 gene loci of statistical significance. Of these loci, 28 genetic variants were closely related to IBD, and 7 single-nucleotide polymorphisms represented novel independent risk loci. In addition, 14 genes and 514 proteins were found to be associated with susceptibility to immune-mediated diseases. Notably, IL1RL1 emerged as a key player, present within pleiotropic genes across multiple protein databases, highlighting its potential as a therapeutic target. Conclusions: This study suggests that the common polygenic determinants between IBD and immune-mediated diseases are widely distributed across the genome. The findings not only support a shared genetic relationship between IBD and immune-mediated diseases but also provide novel therapeutic targets for these diseases.