Crohn's disease (CD) is a chronic inflammatory condition associated with psychological stress and anxiety. Functional magnetic resonance imaging (fMRI) studies have shown differences in brain function between patients with CD and healthy controls (HC). This study aimed to compare the neural correlates of anxiety inindividuals with CD relative to HC, using resting-state fMRI data.

Participants filled in the State-Trait Anxiety Inventory (STAI), a validated tool for measuring anxiety, and underwent an MRI acquisition, including both structural and functional sequences, to identify brain regions associated with anxiety scores.

Seventeen patients with CD and eighteen HC matched for age, education, and sex participated in the study. No significant group differences emerged in the STAI scores. However, resting-state fMRI analysis revealed distinct patterns of functional connectivity associated with anxiety scores for the two study groups. Among CD group, greater STAI scores correlated with increased functional connectivity, whereas, in HC, they correlated with decreased functional connectivity. Significant clusters were found in brain regions belonging to specific resting-state networks (RSNs): (a) Posterior Cingulate Cortex (PCC, within the Default Mode Network), (b) left Middle Frontal Gyrus (within the Left Fronto-Parietal Network), and (c) PCC and right Superior Temporal Gyrus (within the Dorsal Attention Network).

The differential association between functional connectivity and STAI scores observed for CD and HC participants was located in areas within self-referential (Default Mode Network) and cognitive (Left Fronto-Parietal Network and Dorsal Attention Network) RSNs. Our findings suggest that maladaptive/dysfunctional processing of negative emotions and visceral sensitivity may occur in patients with CD.

Optimal treatment strategies for seton use in patients with Crohn's perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF.

Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched. Titles, abstracts, and relevant full texts were screened by 2 reviewers for inclusion using prespecified PICOS-T criteria. Articles published in English between January 1, 1980 and September 6, 2021 were included; animal/in vitro studies and case reports with <5 patients were excluded. Outcomes of interest included rates of complete response/remission and fistula recurrence in patients receiving seton with/without infliximab or biologics. Data were summarized using descriptive statistics.

Overall, 56 studies were included (full texts: n = 43; congress abstracts: n = 13). CPF and clinical outcome definitions were heterogeneous. Rates (range) of complete response/remission varied widely (seton: 13%-75%; seton + infliximab: 23%-100%; seton + biologics: 23%-59%) as did rates for fistula recurrence (seton: 4%-68%; seton + infliximab: 0%-50%; seton + biologics: 0%-17%). Rates of fistula-related reintervention, new fistula or abscess formation, and abscess recurrence were also varied; more consistency was observed regarding the use of patient-reported outcomes. Few studies reported outcomes from pediatric/adolescent patients or HCRU.

Optimal use of seton in patients with CPF remains unclear. International standardization of definitions for CPF and related clinical outcomes are required to permit data comparability and identify the most effective treatment strategies involving seton use in CPF.

The aim of this study was to explore the scientific hotspots related to ultrasound in inflammatory bowel disease (IBD) through bibliometric approaches. The Web of Science Core database was used to identify articles about ultrasound and IBD that were published. We retrieved articles related to ultrasound and IBD from the Science Citation Index Expanded in the Web of Science Core Collection on March 7, 2024. The bibliometric analysis was carried out using Bibliometrix and the VOSviewer. The first article was published in 1979. The average annual growth rate of the publication count was approximately 10.24% during the study period. The USA (135 publications) and Italy (132 publications) were the mainstays in this field. Allocca Mariangela (24 publications) is a prolific author, yet Maaser Christian has the most citations. Regarding journals, the Journal of Crohn's Colitis (68 publications) has the most publications on this topic. In terms of affiliations, the University of Milan (41 publications) has the highest number of publications. The co-occurrence analysis of keywords presented: diagnosis (intestine wall, activity index, etc), gastrointestinal ultrasound, management, pediatric patients. In recent years, "intestinal ultrasound," "infliximab," and "monitoring and healing" were the most active terms within these clusters. There has recently been a profusion of research on the application of ultrasound to IBD. Ultrasound examinations are beneficial tools in IBD diagnosis and assessment of treatment outcomes.

The Crohn's disease exclusion diet (CDED) has been shown to induce remission in adult Crohn's disease (CD) patients. The aim of the study is to provide additional evidence-based validation.

We conducted an open-label, randomized trial on adult CD patients with mild-to-moderate symptoms to assess CDED efficacy in inducing symptomatic remission using Mediterranean diet as control. We evaluate demographic data, body mass index (BMI), Harvey-Bradshaw Index (HBI), faecal calprotectin, and serum inflammatory indices at baseline, 12, and 24 weeks. Bioelectrical impedance analysis (BIA) was used to ensure the safety of the CDED group every 12 weeks.

Twenty-four patients were assigned to CDED, and 21 to controls, with no baseline differences among the parameters considered. Five CDED patients dropped out due to intolerance within the first 6 weeks. At 12 weeks, CDED patients showed significantly lower HBI and higher remission rates than controls. By 24 weeks, remission rates increased (70.8% vs. 38.1% at 12 weeks and 79.2% vs. 42.9% at 24 weeks; p = .027 and p < .0001, respectively), with significantly lower fibrinogen levels in the CDED group. The administration of CDED was associated with a significant decrease in BMI (25.8 kg/m2-24.5 kg/m2, p = .047), although BIA analysis showed a decrease in fat mass (18.2%-15.5%, p < .0001), while fat-free mass and body cellular mass significantly increased at 12 weeks (p = .001 and p = .042, respectively) and remained stable at 24 weeks.

The CDED was effective in inducing remission among patients with mild-to-moderate CD and appeared to be safe and well-accepted.

Inflammatory bowel diseases (IBD) have been associated with an increased long-term risk of coronary artery disease due to chronic systemic inflammation.

To evaluate the risk of major adverse cardiovascular events (MACE) after coronary interventions.

In this nationwide cohort study of adults undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (2012-2022), patients with IBD were propensity score-matched 1:10 to comparators without IBD. The primary outcome was MACE, a composite of acute myocardial infarction, stroke, hospitalisation for heart failure, or mortality. Secondary outcomes included each MACE component, 30-day all-cause readmission, revascularisation and in-hospital outcomes including intensive care unit admission and length of hospital stay. We calculated hazard ratios (HRs) and incidence rates (IRs) using Cox proportional hazards modelling.

We included 987 patients with IBD and 9571 matched comparators. After a median follow-up of 3.5 years, MACE occurred in 488 patients with IBD (49.4%, IR: 96.5/10,000 person-years [PY]) and in 3857 matched comparators (40.3%, IR: 68.9/10,000 PY); HR 1.37 (95% CI, 1.24-1.52). This equates to one additional MACE for every 36 patients with IBD over 10 years. The risk of each MACE component was increased, except for stroke. There were no differences between IBD subtypes or coronary intervention (PCI vs. CABG). Risks were highest in older individuals and elective interventions.

Patients with IBD were at 37% higher risk of MACE after coronary intervention, indicating a need for intensified cardiovascular risk reduction in these high-risk individuals.

Imaging is crucial to assess disease extent, activity, and outcomes in inflammatory bowel disease (IBD). Artificial intelligence (AI) image interpretation requires automated exploitation of studies at scale as an initial step. Here we evaluate natural language processing to classify Crohn's disease (CD) on CTE. From our population representative IBD registry a sample of CD patients (male: 44.6%, median age: 50 IQR37-60) and controls (n = 981 each) CTE reports were extracted and split into training- (n = 1568), development- (n = 196), and testing (n = 198) datasets each with around 200 words and balanced numbers of labels, respectively. Predictive classification was evaluated with CNN, Bi-LSTM, BERT-110M, LLaMA-3.3-70B-Instruct and DeepSeek-R1-Distill-LLaMA-70B. While our custom IBDBERT finetuned on expert IBD knowledge (i.e. ACG, AGA, ECCO guidelines), outperformed rule- and rationale extraction-based classifiers (accuracy 88.6% with pre-tuning learning rate 0.00001, AUC 0.945) in predictive performance, LLaMA, but not DeepSeek achieved overall superior results (accuracy 91.2% vs. 88.9%, F1 0.907 vs. 0.874).

Nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD 1/2) are important cytoplasmic pattern recognition receptors that initiate host immune responses. Dysregulation of NOD signaling is highly associated with inflammatory bowel disease (IBD) and necessitate efficient treatment options. As a key mediator of NOD signals, receptor-interacting protein kinase 2 (RIPK2) was considered as a promising therapeutic target for IBD therapy. However, no approved RIPK2 inhibitors are currently available for clinical use. we screened our in-house compound library using a phenotype-based cell assay and found the compound HYML-122, which a known FLT3 inhibitor currently under clinical investigation, can effectively block the function of RIPK2 kinase and NOD-mediated NF-κB/MAPK activation in mouse cells. Furthermore, HYML-122 significantly inhibited the production of pro-inflammatory cytokines induced by muramyl dipeptide (MDP) in human peripheral blood mononuclear cells (hPBMCs) and MDP-induced peritonitis in mice. In addition, HYML-122 is highly enriched in the intestinal tract, and significantly improve Dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats and dextran sulfate sodium (DSS)-induced colitis in mice. In conclusion, this study presented HYML-122 is a promising RIPK2 inhibitor with potential for further drug development for the treatment of IBD.

There are few data on ustekinumab treatment for Crohn's disease (CD) in a Chinese population. Our study is a real-world retrospective multicenter study aimed at exploring the effectiveness of ustekinumab in CD patients and comparing the effectiveness of first line and second line treatments.

Laboratory indicators, CD activity index (CDAI) and simple endoscopic score for CD (SES-CD) scores of patients at the 8th, 16th and 24th weeks of treatment were collected, and the clinical remission rate, clinical response rate, endoscopic remission rate and endoscopic response rate were calculated, and the patients were divided into first line group and second line group for comparison.

A total of 102 patients were treated with ustekinumab, and 56 patients with a clinical data integrity rate greater than 70% were ultimately included. The clinical remission rate of the patients gradually increased at the 8th, 16th and 24th weeks of treatment, which were 34 cases (60.7%), 37 cases (66.1%) and 49 cases (87.5%), respectively. The clinical response rates for 8th, 16th and 24th weeks were 38 (67.8%), 42 (0.75%) and 51 (91.1%), respectively, and the endoscopic remission rate was 4% (2/50) at the 24th week. The clinical response rates of the first line group were higher than those of the second line group at the 16th and 24th weeks, with statistically significant differences. The clinical response time of patients receiving first line or second line treatment with ustekinumab was different, and the first line treatment group achieved clinical response more quickly.

Ustekinumab is effective in the short-term treatment of CD patients in China, with first line treatment superior to second line treatment and faster than second line treatment.

Proactive dosing based on therapeutic drug monitoring (TDM) of adalimumab is associated with higher rates of sustained corticosteroid-free clinical remission (SCFCR) in children with Crohn's disease (CD) than that with reactive TDM. We aimed to investigate whether proactive dosing of infliximab (IFX) based on TDM is associated with higher rates of endoscopic healing (EH) in pediatric patients with CD than that with clinically based dosing.

We conducted a non-blinded, randomized controlled trial of 112 biologic-naïve children with CD who had responded to IFX induction treatment at 4 centers in South Korea between July 2017 and November 2020. Patients were randomly assigned to receive dosing based on proactive TDM (proactive arm) or clinically based dosing (clinical arm). The primary endpoint was EH at week 54.

The primary endpoint was achieved in 80.0% (40/50) of the proactive arm and 57.1% (28/49) of the clinical arm (P = .025). SCFCR was achieved in 69.6% (39/56) of the clinical arm and 89.3% (50/56) of the proactive arm at week 54 of treatment (P = .019). According to the multivariate logistic regression analysis, the intervention group (proactive arm vs clinical arm) was an independent factor associated with EH (odds ratio, 3.48; 95% confidence interval, 1.26-10.43; P = .019) and SCFCR (odds ratio, 5.50; 95% confidence interval, 1.72-21.61; P = .007).

Dosing based on proactive TDM was superior to clinically based dosing in terms of EH in a randomized controlled trial of pediatric CD. Trial identifier: cris.nih.go.kr: KCT0005190.

Inflammatory bowel disease (IBD) such as ulcerative colitis (UC) is an autoimmune disease characterized by persistent inflammation along the gastrointestinal tract with excessive generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. Here, catalase (CAT)-containing microreactor capsules with long-lasting broad-spectrum ROS/RNS-scavenging capability are developed for the treatment of IBD. In this design, CAT is encapsulated in the dense hydrogel network of calcium alginate (ALG) microspheres, which provides long-term protection of CAT activity in protease-rich intestinal environment. Afterward, the polydopamine (PDA) modification on the surface of CAT@ALG microspheres can provide them bioadhesiveness to achieve prolonged retention in the intestinal tract and broad-spectrum scavenging capability against various types of ROS/RNS beyond hydrogen peroxide. Enteric capsules are further used to protect the CAT@ALG-PDA microspheres from gastric fluid for selective release at the intestinal site. The combined action of PDA and CAT in CAT@ALG-PDA microreactors results in the broad-spectrum scavenging of excess ROS/RNS and regulates redox balance in acute UC rat model, showing satisfactory therapeutic effects superior to the mesalazine and adalimumab at clinically relevant doses without obvious side effects. This work highlights that these CAT@ALG-PDA capsules can act as long-acting broad-spectrum ROS/RNS reactors, promising for IBD treatment.

We detect and interactively visualize occurrence, frequency, sequence, and clustering of extraintestinal manifestations (EIM) and associated immune disorders (AID) in 30,334 inflammatory bowel disease (IBD) patients (Crohn's disease (CD) n = 15924, ulcerative colitis (UC) n = 11718, IBD unclassified, IBD-U n = 2692, 52% female, median age 40 years (IQR: 25)) with artificial intelligence (AI). 57% (CD > UC 60% vs. 54%, p < 0.00001) had one or more EIM and/or AID. Mental, musculoskeletal and genitourinary disorders were most frequently associated with IBD: 18% (CD vs. UC 19% vs. 16%, p < 0.00001), 17% (CD vs. UC 20% vs. 15%, p < 0.00001) and 11% (CD vs. UC 13% vs. 9%, p < 0.00001), respectively. AI detected 4 vs. 5 vs. 5 distinct EIM/AID communities with 420 vs. 396 vs. 467 nodes and 11,492 vs. 9116 vs. 16,807 edges (links) in CD vs. UC vs. IBD, respectively. Our newly developed interactive free web app shows previously unknown communities, relationships, and temporal patterns-the diseasome and interactome.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides. A mutation in the same area of the mouse genome by Genentech scientists (T.Y., M.K.) resulted in a similar but not identical phenotype.

Here, we compare histopathological, cellular, and molecular features of the strains and propose reasons for their distinct phenotypes. First, while homozygous TNFΔARE mice develop severe arthritis and die after weaning, homozygous Genentech TNFΔARE (ΔG/ΔG) mice have normal lifespans, and males are often fertile.

We found that while the ileitic phenotype had peaked at 12 weeks of age in all mice, colitis progressed mostly after 20 weeks of age in heterozygous mice. Their variably penetrant arthritic phenotype progressed mostly after 20 weeks, also in heterozygous mice from both strains. There was expansion of central memory T and B cells in lymphoid organs of TNF-overproducing strains and their transcriptional profile shared well-known pathogenetic pathways with human IBD. Finally, we found differences in the mutated sequences within the ARE regions of the TNF gene and in their microbiota composition and genetic background. These differences likely explain their phenotypic differences.

In summary, we describe a different strain of TNF-overproducing mice with an overlapping, yet not identical phenotype, which may have differential applications than the original strain.

Population pharmacokinetic (popPK) models are essential tools for optimizing ustekinumab (UST) dosing for the treatment of inflammatory bowel disease (IBD) through therapeutic drug monitoring. The external validation of these models is necessary to ensure their predictive performance and clinical utility. The aim of the study was to externally validate 4 published popPK models of UST in a real-world cohort of patients with IBD using prediction-based and simulation-based diagnostics, as well as Bayesian forecasting.

Four popPK models of UST, identified through a systematic literature review, were evaluated using data from 99 patients with IBD and 374 serum UST concentrations. Predictive performance and Bayesian forecasting were assessed using statistical metrics, including mean prediction error, median prediction error (MDPE), and median absolute prediction error (MADPE). The acceptability criteria (MDPE ±20%, MADPE ≤30%, F20 ≥35%, and F30 ≥50%) were applied.

None of the models satisfied the predefined acceptability criteria. The Xu et al model demonstrated the best performance, achieving an MDPE of 19.55% and the lowest RMSPE (2.88 mcg/mL), but F20 (20.1%) and F30 (32.4%) values fell below thresholds. The model proposed by Adedokun et al showed strong results in simulation-based diagnostics, with only 5.6% of the observed concentrations outside the prediction interval.

The models developed by Xu et al and Adedokun et al exhibited the most promising predictive performance and potential clinical applicability for model-informed precision dosing. Refinements to these models and further research are required to enhance their use in personalized UST therapies for IBD.

understanding the relationship between ustekinumab (UST) exposure and clinical outcomes in inflammatory bowel disease (IBD) induction is crucial. However, evidence remains limited, highlighting the need to comprehend UST's pharmacokinetic variability for tailored treatments.

this study aimed to investigate the association between UST exposure during the induction phase and clinical outcomes and identifying factors associated with UST exposure during this period.

a retrospective observational study was conducted on a cohort of consecutive IBD patients. The primary endpoint was to assess the association between UST exposure at week 8 and both clinical and biochemical remission at week 26, as well as the absence of disease flare-ups during the initial six months of treatment. The secondary endpoint was to investigate the relationship between baseline characteristics and UST exposure at week 8.

a total of 56 IBD patients were included. Variables associated with adequate UST exposure included baseline fecal calprotectin < 500 µg/g (OR: 7.72 [95 % CI: 1.75-34.03]) and female sex (OR: 4.56 [95 % CI: 1.12-18.60]). A cut-off UST trough levels of 8.3 μg/ml yielded an area under the curve (AUC) of 0.74 (95 % CI: 0.58-0.90, p = 0.021) to predict normal fecal calprotectin levels, and 8.6 µg/ml resulted in an AUC of 0.724 (95 % CI: 0.558-0.863) to predict clinical remission.

this study demonstrates a significant association between UST concentrations and clinical and biochemical remission in IBD patients. Results suggest that standard induction doses may not be sufficient for all patients, highlighting the importance of treatment individualization to optimize outcomes.

Inflammatory bowel diseases (IBDs) are relapsing, remitting inflammatory diseases of the intestinal tract. Familial aggregation and genome-wide association studies revealed susceptibility variants that point toward a combination of innate immune and adaptive immune dysregulation that in concert with environmental factors, such as our microbiome, can initiate and perpetuate inflammation. Innate immune perturbations include functional abnormalities in the intestinal barrier, endoplasmic reticulum stress, and abnormal recognition of microbes. Adaptive immune changes include dysregulation of cytokines, regulatory T cells, and leukocyte migration. IBD is linked with an abnormal wound-healing response leading to fibrosis. This article summarizes key pathogenic mechanisms in the pathogenesis of IBDs.

Background/Objectives: Crohn's disease is a chronic inflammatory condition with periods of exacerbation and remission that can involve any part of the gastrointestinal tract. The basic intestinal manifestation is frequently accompanied by extraintestinal involvement and may lead to complications such as perforations, fistulas and abscesses. Despite Crohn's disease being the most common reason of intestinal perforation, the other causes should be considered as well. Internalization of a foreign body, although rare, may still occur, especially in the pediatric population. Methods: The following case report presents the medical history of an 11-year-old patient who developed an enterocutaneous fistula two years after the diagnosis of Crohn's disease. Data analysis was carried out on the basis of patient medical records. Results: The fistula formed in the course of biological treatment during a period free of other symptoms indicating disease exacerbation. The imaging tests revealed the presence of a foreign body in the gastrointestinal tract, which could have been a potential cause of the observed inflammation that resulted in the development of the fistula. Conclusions: The presented case report as well as the literature indicate a correlation between the formation of intestinal fistulas and an active disease process. However, in the absence of symptoms of Crohn's disease exacerbation, other causes should be considered.

Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration in colonic mucosa, accompanied by a defective epithelial barrier. Proteus mirabilis (P. mirabilis) bacterium is a putative intestinal pathogen with invasive ability, yet its role in UC inflammation and gut barrier disruption is unclear. This study aims to investigate its epidemiological presence, pathogenic roles and preventive strategy during UC inflammation.

P. mirabilis culture and PCR amplification of the P. mirabilis-specific ureR gene were used to detect fecal P. mirabilis and determine its prevalence in UC and control stool specimens. P. mirabilis isolated from UC stool specimens was gavaged into dextran sulfate sodium (DSS)-treated mice. Inflammation and the mucus layer of colons were assessed through histological examination and cytokine quantification. Bacteriophages were screened and used to eliminate P. mirabilis in colitis animals.

The fecal P. mirabilis bacteria were detected by PCR amplification of P. mirabilis-specific ureR gene. Of 41 UC patients, 65.9% patients were P. mirabilis positive, which was significantly higher than the controls. Administration of P. mirabilis aggravated DSS-induced colitis symptom and mucosal inflammation in mice. Interestingly, the colonic mucus layer, an essential component of the epithelial barrier, of the animals was dramatically disrupted, which was consistent with the alteration of human UC colon. The disrupted mucus layer was mediated by the down-regulation of IL-18 in intestinal epithelium. Importantly, a bacteriophage cocktail targeting P. mirabilis could restore the mucus barrier and alleviate the enteric inflammation. Thus, our results suggest that P. mirabilis is a UC pathobiont bacterium, which exacerbates the severity of UC inflammation owing to down-regulation of mucin production and IL-18 expression. Bacteriophage-mediated elimination of P. mirabilis may be effective in limiting UC inflammation.

Inflammatory bowel disease (IBD) is a chronic and refractory disease with increasing incidence, adversely impacting millions of patients worldwide. Current therapeutic strategies for IBD often exhibit considerable adverse effects, limited efficacy, and a high tendency for recurrence, highlighting the urgent need for novel therapeutic agents. Hydrogel, a three-dimensional hydrophilic network polymer material known for its excellent biocompatibility and responsiveness to stimuli, has been effectively utilized as a drug carrier across various therapeutic systems. The hydrogels' application in IBD treatment holds significant promise for enhancing therapeutic outcomes. This review synthesizes recent advancements in leveraging hydrogels as drug carriers for IBD management. The discussion encompasses the response mechanisms of hydrogels, their application in IBD therapy, and methods of administration. As drug delivery matrices, hydrogels exhibit considerable potential for treating IBD.

There is ongoing debate regarding the benefits of extended mesenteric excision (EME) versus limited mesenteric excision (LME) in intestinal resection for Crohn's disease (CD). Some studies suggest that EME may reduce surgical recurrence, which is defined as the need for reoperation due to disease complications or insufficient response to therapy, when compared with LME. This systematic review and meta-analysis aims to compare postoperative complications, surgical recurrence, and endoscopic recurrence in patients undergoing EME versus LME for CD.

MEDLINE, Cochrane, the Central Register of Clinical Trials, Scopus and Web of Science databases were searched for studies published through April 2024. Odds ratios (OR) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with Cochran's Q test and I2 statistics, with p-values < 0.10 and I2 > 25% considered significant. Statistical analyses were performed using R software, version 4.4.1.

One randomized controlled trial (RCT) and five observational studies were included, totaling 4498 patients, of whom 1059 (23.5%) underwent EME and 3439 (76.5%) LME. EME was associated with a lower surgical recurrence rate (5% versus 15%; OR 0.31; 95% CI 0.12-0.84; p = 0.021; I2 = 47%). No significant differences were observed between EME and LME for overall complications, Clavien-Dindo ≥ 3 events, bleeding requiring transfusion, anastomotic leaks, intraabdominal abscesses, surgical site infections (SSIs), reoperations, readmissions, ileus, endoscopic recurrences, operative times, or hospital stays.

EME was associated with a significant reduction in surgical recurrence compared with LME, without differences in endoscopic recurrence or postoperative complication rates.

Regulatory T cells (Tregs) are key regulators in maintaining tissue homeostasis. Disrupted immune homeostasis is associated with Crohn's disease (CD) pathogenesis. Thus, Treg therapy represents a promising long-acting treatment to restore immune balance in the diseased intestine. Chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer treatment. This innovative approach also provides the opportunity to improve therapy for CD. By targeting a disease-relevant protein, interleukin-23 receptor (IL23R), we engineered Tregs expressing IL23R-CAR for treating active CD.

Intestinal IL23R expression from active CD was verified by immunohistochemical analysis. Phenotypic and functional characteristics of IL23R-CAR Tregs were assessed using in vitro assays and their migration capacity was monitored in a xenograft tumor model. Transcriptomic and proteomic analyses were performed to associate molecular profiles with IL23R-CAR Treg activation against colon biopsy-derived cells from active CD patients.

Our study showed that IL23R-CAR displayed negligible tonic signaling and a strong signal-to-noise ratio. IL23R-CAR Tregs maintained regulatory phenotype during in vitro expansion, even when chronically exposed to proinflammatory cytokines and target antigen. IL23R engagement on IL23R-CAR Tregs triggered CAR-specific activation and significantly enhanced their suppressive activity. Also, IL23R-CAR Tregs migrated to IL23R-expressing tissue in humanized mice. Finally, IL23R-CAR Tregs elicited a specific activation against colon biopsy-derived cells from active CD, suggesting an efficient CAR engagement in active CD. Molecular profiling of CD patient biopsies also revealed transcriptomic and proteomic patterns associated with IL23R-CAR activation.

Overall, our results demonstrate that IL23R-CAR Tregs represent a promising therapy for active CD.

We investigated the relationship between nut and legume intake and risk of Crohn's disease (CD) and ulcerative colitis (UC).

We conducted a prospective cohort study of 223 283 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (1986-2017), excluding those with inflammatory bowel disease (IBD) at baseline. Food frequency questionnaires were used to calculate nut and legume intake. Inflammatory bowel disease was self-reported on questionnaires and confirmed via blinded record review. Using Cox proportional hazards models, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CD and UC according to categories of nut and legume intake.

In over 5 460 315 person-years of follow-up (CD = 371, UC = 481), neither nut nor legume intake was associated with CD or UC risk. Compared to those who never consumed nuts, those who consumed nuts ≥2 times/week had an aHR = 0.96 (95% CI, 0.63-1.47; Ptrend = 0.57) for CD and 1.30 (95% CI, 0.92-1.84; Ptrend = 0.36) for UC. Compared to those who consumed legumes 0-3 times/month, those who consumed legumes ≥4 times/week had an aHR of 1.26 (95% CI, 0.78-2.04; Ptrend = 0.59) for CD and 0.72 (95% CI, 0.44-1.18; Ptrend = 0.20) for UC. Baseline BMI modified the relationship between nut intake and CD risk (Pint = 0.03). In those with BMI ≥25, the aHR for CD was 0.14 (95% CI, 0.03-0.56; P = .006) per additional serving/day of nuts compared with 0.88 (95% CI, 0.45-1.74; P = .72) for those with BMI <25.

Nut and legume intake were not associated with CD or UC risk. However, higher nut intake decreased CD risk in overweight or obese individuals. Thus, personalized-risk stratification, rather than generalized dietary recommendations, may be important for IBD prevention strategies.

Microbes have a profound impact on human health. Identifying disease-associated microbes would provide helpful guidance for drug development and disease treatment. Through an enormous experimental effort, limited disease-associated microbes have been determined. Accurate computational approaches are needed to predict potential microbe-disease associations for biomedical screening. In this study, we present an ensemble learning framework entitled SABMDA to improve microbe-disease association inference. We first integrate multi-source of information from both microbes and diseases, and develop two matrix completion algorithms to predict microbe-disease associations successively. Ablation tests show combining the two matrix completion algorithms can receive better prediction performance. Moreover, comprehensive experiments, including cross-validations and independent test, demonstrate that SABMDA outperforms seven recent baseline methods significantly. Finally, we apply SABMDA to three diseases to predict their associated microbes, and results show SABMDA's remarkable prediction ability in real situations.

Background Patients with inflammatory bowel disease (IBD) have a higher risk of adverse outcomes after total hip arthroplasty (THA) and total knee arthroplasty (TKA) compared to the general population. However, existing literature has not fully elucidated the risk of IBD patients to undergo arthroplasty for treatment of arthritis. Therefore, the purpose of this study is to understand the incidence of arthroplasty and osteoarthritis, enteropathic arthritis, or inflammatory polyarthropathies in patients with IBD compared to the general population. Methods A retrospective cohort analysis was conducted using the TriNetX research database to identify all patients who experienced the primary outcomes between 2004 and 2024. Two cohorts were stratified by a diagnosis of IBD and propensity score matched (1:1) to mitigate baseline differences in demographics and comorbidities. Results After propensity matching, each cohort contained 531,263 patients who were included for analysis. Patients with IBD were significantly less likely to undergo THA (OR 0.853, 95% CI 0.804-0.906) and TKA (OR 0.830, 95% CI 0.788-0.874) and less likely to incur a diagnosis of hip osteoarthritis (OR 0.943, 95% CI 0.922-0.965) or knee osteoarthritis (OR 0.794, 95% CI 0.780-0.808). Conversely, IBD patients were significantly more likely to incur a diagnosis of enteropathic arthropathy (OR 287.9, 95% CI 181.3-457.5) or inflammatory polyarthropathies (OR 1.390, 95% CI 1.365-1.414). Conclusions Patients with IBD are less likely to undergo THA and TKA despite the association between IBD and arthritis. These findings underscore the importance of tailored treatment strategies for joint-related complications in IBD patients and highlight the need for further research to optimize surgical outcomes in this population.

Disruption of the intestinal epithelial barrier results in increased permeability and is a key factor in the onset and progression of Crohn's disease (CD). The protein SPARC is primarily involved in cell interaction and migration, but its specific role in the intestinal epithelial barrier remains unclear. This study demonstrates that SPARC is significantly overexpressed in both CD patients and murine models of colitis. Furthermore, mice deficient in SPARC exhibits resistance to chemically induced colitis, a phenomenon associated with the modulation of barrier-associated proteins. Mechanistically, it is elucidated that SPARC competitively binds to OTUD4 in conjunction with MYD88, facilitating the translocation of p65 from the cytoplasm to the nucleus and subsequent activation of the p65-MLCK/MLC2 pathway, thereby compromising barrier integrity. Additionally, it is identified that the elevated expression of SPARC in CD is regulated via the METTL3-YTHDF1 axis. These findings indicate that SPARC levels are elevated in patients with CD and in colitis-induced mice, leading to intestinal barrier damage through direct interaction with OTUD4 and subsequent activation of the MYD88/p65/MLCK/MLC2 signaling pathway. Consequently, targeting SPARC or the OTUD4/MYD88/p65/MLCK/MLC2 axis may offer novel insights into the molecular mechanisms underlying CD and represent a potential therapeutic strategy.

Inflammatory bowel disease (IBD) refers to a group of chronic, recurrent intestinal inflammatory conditions with a complex cause and unclear underlying mechanisms. It includes two main types: Ulcerative colitis (UC) and Crohn's disease (CD). The conventional treatment of IBD mainly includes 5-aminosalicylates, glucocorticoids, and immunosuppressive drugs, which have their limitations. Recent advancements in IBD research have expanded treatment options, with biological agents playing a key role. Anti-tumor necrosis factor alpha has emerged as the first-line therapy for moderate to severe IBD. Anti-integrin antibodies have also become important for the treatment, and vedolizumab is often used in cases of anti-tumor necrosis factor-alpha failure and intolerance to other treatments. Other biological agents are being tested in clinical trials at different stages. This article reviews the efficacy and safety of the primary biological therapies for IBD and provides a comprehensive analysis of the current clinical challenges associated with the disease.

Crohn's disease is a chronic inflammatory bowel disease and, despite an increase in the available drug treatments, many patients will still require surgery at some point in their disease course. Stricturing and penetrating phenotypes of Crohn's disease are less likely to respond to our current medical treatment and, therefore, surgical intervention may be required. This is most commonly elective, planned surgery, thereby affording the opportunity to optimize medications, nutritional and inflammatory status, and steroid use. Poor nutritional status and previous surgery increase the risk of postoperative complications. Preoperative optimization has three main goals: reduction of postoperative complications; reduction of reoperation rates; and reduction of postoperative recurrence rates. A literature search was completed using PubMed, Embase, and Ovid using the search term "preoperative optimization in Crohn's disease", and it included both adult and pediatric studies, excluding those for perianal Crohn's disease. In this narrative review, we examine the role of nutritional intervention, medical optimization pre and postoperatively, and the role of personalized prehabilitation in the reduction of postoperative complications. We demonstrate that these may all yield better postoperative outcomes for patients with Crohn's disease undergoing elective surgery, although the evidence is somewhat limited and there is a requirement for more prospective randomized controlled trials to implement their role into standard practice or guidelines.

Dual-energy computed tomography enterography (DECTE) has significantly improved gastrointestinal imaging quality. Double-balloon endoscopy (DBE) has enabled comprehensive visualization of the small intestinal mucosa. This study aimed to assess the diagnostic efficacy of small-intestine DECTE and DBE for small bowel Crohn's disease (CD).

This retrospective study was conducted between 1 July 2016 and 1 November 2023 at the First Affiliated Hospital of Soochow University. The study included 72 CD patients who underwent both DECTE and DBE, with 4 patients repeating both procedures within 3 months.

The diagnostic rate of small bowel CD using DBE was 80.3%, which was higher than that using DECTE (65.8%, P = 0.044). The combined small bowel CD diagnostic rate was 89.5%, which was higher than that of DECTE alone (P < 0.001). The detection rate of stenosis using DBE was 46.1%, which was higher than that using DECTE (13.2%; P < 0.001). The combined detection rate of stenosis was 52.6%, which was higher than that of DECTE alone (P < 0.001). For ulcers, DBE had a higher detection rate (73.7%) than DECTE (7.9%; P < 0.001). The combined ulcer detection rate was 76.3%, which was higher than that of DECTE alone (P < 0.001). The detection rate of long ulcers (≥ 2 cm) and non-ileocecal ulcers by DBE were both 17.9%. For patients with abdominal pain, DBE had a diagnostic rate of 79.4%, higher than 63.5% of DECTE (χ2 = 3.889, P = 0.049). The combined diagnostic rate was 87.3%, which was higher than that of DECTE alone (χ2 = 9.626, P = 0.002). For patients with diarrhoea, the DBE's diagnostic rates were 86.8% and 68.4% for DECTE (P = 0.097). The combined diagnostic rate was 94.7%, higher than DECTE alone (χ2 = 7.092, P = 0.008). For patients with other symptoms, such as abdominal distension or vomiting, the DBE diagnostic rate was 79.4% compared with 61.8% for DECTE (P = 0.183). The combined diagnostic rate was higher than DECTE alone (χ2 = 6.620, P = 0.010). Furthermore, notable differences in C-reactive protein, erythrocyte sedimentation rate, faecal calprotectin, haemoglobin, platelet count, albumin, haematocrit, Crohn's Disease Activity Index scores, and Simple Endoscopic Score for Crohn's Disease scores were observed between ulcer-positive and ulcer-negative patients detected by DBE (P < 0.05), whereas DECTE did not show significant differences (P > 0.05).

DBE or the combined use of DECTE and DBE provides superior diagnostic performance for small bowel CD, particularly in detecting stenosis and ulcers, compared with DECTE alone. DBE can be used to identify long ulcers and non-ileocecal ulcers. Moreover, DBE helps diagnose small bowel CD across different clinical manifestations and assess disease activity in various inflammatory states.

The Stool Frequency (SF) and Abdominal Pain (AP) items from the Crohn's Disease Activity Index are together referred to as the "Patient Reported Outcome" (PRO). The SF item measures the number of very soft/liquid stools and the AP item measures abdominal pain severity, which are common Crohn's disease (CD) symptoms that patients consider important to treat. This study evaluated the psychometric properties of both PRO items separately and estimated thresholds for clinical remission in moderately to severely active CD.

The measurement properties of the PRO items were analyzed using pooled data from VIVID-1 (NCT03926130), a Phase 3, randomized, placebo- and active-controlled study in adults with moderately to severely active CD. Analyses used weekly average scores of the SF and AP items at Weeks 0 (Baseline), 4, 12, and 52. Remission thresholds were estimated using the Patient Global Rating of Severity (PGRS) and Patient Global Impression of Change (PGIC) as primary anchors as well as qualitative evidence from exit interviews.

Data from 1065 participants (mean age: 36.2 years [standard deviation: 13 years]) were analyzed. During the trial, scores improved for both PRO items. Both items demonstrated moderate-to-good test-retest reliability for participants defined as stable based on PGRS and PGIC. Most correlations of related assessments were moderate (0.30≤|ρ| <0.70) with SF and moderate-to-large (0.30≤|ρ| ≤0.90) with AP. By contrast, as anticipated, both items had weak correlations (|ρ| <0.30) with endoscopic and laboratory assessments. The PRO items could discriminate between groups of participants known to differ based on other assessments. The PRO items were able to detect change, as score changes in both items between Baseline and Weeks 12 and 52 differed significantly between most PGRS and PGIC categories. Anchor-based analyses combined with responses from the exit interviews suggested that an SF score of ≤ 3 and an AP score of ≤ 1 could together represent clinical remission.

These results support the reliability, construct-validity, and responsiveness of both PRO items in moderately to severely active CD and confirm previously suggested scores for both items that could represent clinical remission.

Clinicaltrials.gov, NCT03926130. Registered 23 April 2019, https://clinicaltrials.gov/study/NCT03926130 .

Sarcopenia is an age-related condition marked by muscle loss and weakened muscular strength. It is a new predictor of poor clinical outcomes in several illnesses. The association between sarcopenia and poor outcomes in Crohn's disease is still debated. Our main objective is to evaluate the impact of sarcopenia vs non-sarcopenia on the development of adverse outcomes in patients with Crohn's disease.

We conducted a systematic review and meta-analysis synthesizing observational studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane until October 1, 2024. The odd ratio (OR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used.

There were fourteen studies with a total of 2334 patients. The sarcopenia group was associated with a higher risk of hospitalization (OR, 1.87 with 95% CI [1.19-2.93], P = 0.006) and developing abscess (OR, 5.03 with 95% CI [2.05-12.38], P = 0.0004). However, there was no statistically significant difference between sarcopenia and non-sarcopenia groups, regarding the need for surgery (OR, 1.12 with 95% CI [0.5-2.5], P = 0.79), loss of biological response (OR, 1.11 with 95% CI [0.34-3.66], P = 0.86), need for biological therapy (OR, 0.77 with 95% CI [0.43-1.36], P = 0.36), and surgical site leak (OR, 2.01 with 95% CI [0.66-6.18], P = 0.22).

Our study showed that sarcopenia is associated with an increased risk of hospitalization and abscess formation in patients with Crohn's. However, sarcopenia does not significantly affect the need for surgery, loss of biological response, need for biological therapy, or the occurrence of surgical site leaks. Further studies are required to explore the mechanisms underlying these associations.

Fatigue is a burdensome, under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104).

Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200 mg, 600 mg, or 1000 mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300 mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300 mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient.

At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers.

Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.

There is a need for efficacious therapies for patients with Crohn's disease that are better tolerated and more durable than available treatments. We aimed to evaluate the efficacy and safety of filgotinib, an oral Janus kinase 1 preferential inhibitor, for treating Crohn's disease.

This phase 3, double-blind, randomised, placebo-controlled trial was conducted in 371 centres in 39 countries. Eligible patients were aged 18-75 years with moderately to severely active Crohn's disease for at least 3 months before enrolment. Patients were enrolled into one of two induction studies on the basis of their experience with biological agents (induction study A included biologic-naive and later biologic-experienced patients and induction study B included biologic-experienced patients). In both induction studies, patients were randomly assigned (1:1:1), using an interactive web response system, to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once daily for 11 weeks. Patients who received filgotinib and had two-item patient-reported outcome (PRO2) clinical remission or an endoscopic response at week 10 were re-randomised (2:1) to receive their induction dose or placebo orally, once daily to the end of week 58 in the maintenance study. Co-primary endpoints were PRO2 clinical remission and an endoscopic response at week 10 (induction studies) and week 58 (maintenance study). PRO2 clinical remission was defined as an abdominal pain subscore of not more than 1 and a liquid or very soft stool frequency subscore of not more than 3 (from eDiary data) and endoscopic response was defined as a reduction of at least 50% in Simple Endoscopic Score for Crohn's disease from induction baseline (from central reading of endoscopy). For the induction studies, efficacy was assessed in all randomly assigned patients who received at least one dose of study drug. For the maintenance study, efficacy was assessed in all patients from either filgotinib treatment group in the induction studies who reached PRO2 clinical remission or an endoscopic response at week 10, and who were re-randomised and received at least one dose of study drug in the maintenance study. Patients who received placebo throughout the induction and maintenance studies were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of study drug. This trial is complete and is registered with ClinicalTrials.gov, NCT02914561.

Between Oct 31, 2016, and Nov 11, 2022, 2634 patients were screened, of whom 1372 were enrolled (induction study A: n=707, induction study B: n=665, and maintenance study: n=481). There were 346 (49%) women and 358 (51%) men in induction study A, 356 (54%) women and 303 (46%) men in induction study B, and 242 women (51%) and 236 men (49%) in the maintenance study. Significantly more patients had PRO2 clinical remission at week 10 with filgotinib 200 mg than with placebo in induction study B (29·7% vs 17·9%, difference 11·9%; 95% CI 3·7 to 20·2, p=0·0039) but not induction study A (32·9% vs 25·7%, 6·9%; -1·4 to 15·2, p=0·0963); there was no significant difference for endoscopic response (induction study A: 23·9% vs 18·1%, difference 5·5%; 95% CI -2·0 to 12·9, p=0·1365; induction study B: 11·9% vs 11·4%, 0·1%; -6·5 to 6·6, p=0·9797). At week 58, both co-primary endpoints were reported in greater proportions of patients who received filgotinib 200 mg than in those who received placebo (PRO2 clinical remission: 43·8% vs 26·4%, difference 16·8%; 95% CI 2·0 to 31·6, p=0·0382; endoscopic response: 30·4% vs 9·4%, difference 20·6%; 95% CI 8·2 to 33·1, p=0·0038). Co-primary endpoints were not met for filgotinib 100 mg in any study. In the induction studies, the most frequently reported treatment-emergent adverse events (TEAEs; ≥5% of patients in any group) were abdominal pain; arthralgia; an exacerbation, flare, or worsening of Crohn's disease; headache; nasopharyngitis; nausea; and pyrexia. In the maintenance study, the most frequently reported TEAEs (≥5% of patients in any filgotinib or associated placebo group) were those reported in the induction studies (except for headache) and abdominal distension, upper abdominal pain, anaemia, and flatulence. Serious TEAEs were reported in 49 patients in induction study A (18 [8%]) of 222 patients in the filgotinib 200 mg group, 16 [7%] of 245 patients in the filgotinib 100 mg group, and 15 [6%] of 237 patients in the placebo group), 81 patients in induction study B (19 [9%] of 202 patients in the filgotinib 200 mg group, 36 [16%] of 228 patients in the filgotinib 100 mg group, and 26 [11%] of 229 patients in the placebo group), and 49 patients in the maintenance study (13 [11%] of 118 patients in the filgotinib 200 mg-filgotinib 200 mg group, five [9%] of 56 patients in the filgotinib 200 mg-placebo group, 14 [13%] of 104 patients in the filgotinib 100 mg-filgotinib 100 mg group, three [5%] of 55 patients in the filgotinib 100 mg-placebo group, and 14 [10%] of 145 patients in the placebo-placebo group). No deaths were reported during the induction and maintenance studies.

Filgotinib 200 mg did not meet the co-primary endpoints of clinical remission and an endoscopic response at week 10, but did meet the co-primary endpoints at week 58. Filgotinib treatment was well tolerated, and no new safety signals were reported.

Galapagos.

Inflammatory bowel disease (IBD) is usually diagnosed when symptomatic. Prognosis and evolution of preclinical IBD is largely unknown. However, colorectal cancer screening programs (CRCSP) detect a subset of patients with IBD with no symptoms. The aim of this study was to describe the natural history of asymptomatic IBD diagnosed through CRCSP.

An observational, longitudinal, and retrospective study was performed at 22 centers in Catalonia between January 2010 and December 2019 including patients with asymptomatic IBD detected in the CRCSP. Demographic data and IBD characteristics, evolution, and treatment were recorded. Descriptive statistics and Kaplan-Meier analysis were used for the analysis. Data were given separately for IBD, Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBDU).

One hundred eighty-eight patients were included: 103 UC (54.8%), 60 CD (31.9%), and 25 IBDU (13.3%). Sixty-six (35.1%) were women, and the average age was 59.9 ± 5.9 years. Sixty-four patients (34.0%) developed symptoms after a median follow-up of 35.6 months. Diarrhea was the most frequent symptom for CD and IBDU (25.4% and 11.5%, respectively) and blood in stools for UC (21.4%). The median time to first symptom was 11.6 months. Treatment was prescribed in 135 patients (72.2%); mesalazine was the most prescribed drug (123 patients; 65.4%). Thirteen patients (6.9%) required biological treatment. None underwent surgery.

Around one-third of asymptomatic patients with IBD developed symptoms after a medium follow-up of 3 years. Only 6.9% required biological treatment, and none required surgery. Overall, prognosis of asymptomatic IBD seems better.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is primarily known for its gastrointestinal manifestations. However, emerging evidence suggests a potential link between IBD and an increased risk of stroke, likely mediated by chronic systemic inflammation, endothelial dysfunction, and a prothrombotic state. Despite this growing recognition, the exact mechanisms and extent of this association remain unclear, highlighting a critical knowledge gap. This review aims to systematically analyze the association between IBD and stroke, exploring the underlying vascular mechanisms and identifying potential risk factors contributing to cerebrovascular events in IBD patients. A comprehensive literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, Scopus, and Google Scholar using keywords such as "IBD," "Stroke," "Chronic inflammation," "Cerebrovascular risk," and "Gut-brain axis." After screening 150 studies and applying inclusion and exclusion criteria, six studies were included in the final synthesis. The findings suggest that chronic inflammation in IBD plays a key role in increasing stroke risk through endothelial dysfunction and a heightened prothrombotic state, with additional risk factors such as atrial fibrillation during active IBD flares further contributing to cerebrovascular events. While biologic therapies, including tumor necrosis factor (TNF)-alpha inhibitors, are effective in reducing systemic inflammation, their impact on mitigating stroke risk remains inconclusive. Given the potential role of IBD as an independent risk factor for stroke, a multidisciplinary approach to management is crucial. Addressing modifiable risk factors through pharmacologic interventions such as biologics, statins, and antiplatelet agents, alongside lifestyle modifications, could help reduce cerebrovascular complications in IBD patients. Further research is needed to explore personalized therapeutic strategies and establish clearer preventive guidelines for this at-risk population.