Gut microbial composition alters in some special situations, such as in ulcerative colits (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery. The aim of our study was to determine the composition of the intestinal microbiome in UC patients after IPAA surgery, compared with UC patients, familial adenomatous polyposis (FAP) patients after IPAA surgery and healthy controls. Clinical data of patients, blood and faecal samples were collected. Faecal microbiota structure was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. Overall, 56 patients were enrolled. Compared to the Healthy group, both the Pouch active and UC active groups had higher Enterobacteriaceae, Enterococcaceae and Pasteurellaceae abundance. The Pouch and UC groups showed distinct separation based on their alpha and beta bacterial diversities. The UC group had higher Prevotellaceae, Rikenellaceae, Ruminococcaceae abundance compared to the Pouch active group. Pouch and FAP participants showed similar bacterial community composition. There was no significant difference in the bacterial abundance between the active and inactive subgroups of the Pouch or UC groups. Gut microbiome and anatomical status together construct a functional unit that has influence on diversity, in addition to intestinal inflammation that is a part of the pathomechanism in UC.

Background/Objectives: Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn’s disease (CD) are limited. Methods: We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. Results: A total of 246 patients (mean age: 40.5 ± 14.5 years; 131 UC and 115 CD) were included with a median follow-up of 7.5 months. Among the CD patients receiving upadacitinib (n = 115), 76.2% achieved clinical remission (CR) at week 12. Furthermore, 59.5% of the upadacitinib-treated UC patients (n = 100) experienced CR at week 8. Corticosteroid-free CR (CSFCR) was achieved by 76.9% of the CD patients and 80.6% of the UC patients at week 24, while 50.0% and 36.1% experienced endoscopic remission. At week 52, 66.7% of the CD and 86.2% of the UC patients achieved CSFCR, whereas 54.5% and 52.9% had endoscopic remission. In UC, the effectiveness of upadacitinib was not compromised by prior tofacitinib failure, while the upadacitinib-treated CD patients with stricturing and penetrating disease were less likely to achieve CR by the end of the induction phase (p = 0.04). C-reactive protein (p[CD] < 0.0001; p[UC] < 0.0001) and faecal calprotectin (p[CD] < 0.0001; p[UC] = 0.02) decreased significantly in both patient groups as early as week 2. Among the filgotinib-treated UC patients (n = 31), 28.6% were in CR at week 12. At week 24 and 52, 59.1% and 60% achieved CSFCR, while 0.0% and 20.0% had endoscopic remission. Both C-reactive protein (p = 0.04) and faecal calprotectin (p = 0.04) decreased significantly by week 12. Hyperlipidaemia (9.7–9.8%) was the most common adverse event. Conclusions: Selective JAKis are rapidly effective and safe for treating refractory, moderate-to-severe CD and UC.

Background: In patients with inflammatory bowel disease (IBD), Crohn’s disease (CD), and ulcerative colitis (UC), numerous cases of exacerbations could be observed after colonoscopy, raising the possible pathogenetic effect of colonic microbiota alterations in IBD flare. Objectives: We aimed to investigate the changes in the fecal microbiota composition in IBD patients influenced by the bowel preparation with sodium picosulfate. Design: We enrolled patients with IBD undergoing bowel preparation for colonoscopy in the prospective cohort study. The control group (Con) comprised non-IBD patients who underwent colonoscopy. Clinical data, blood, and stool samples were collected before colonoscopy (timepoint A), 3 days later (timepoint B), and 4 weeks later (timepoint C). Methods: Disease activity and gut microbiota changes were assessed at each timepoint. Fecal microbiota structure – at family level – was determined by sequencing the V4 region of the 16S rRNA gene. Statistical analysis included differential abundance analysis and Mann–Whitney tests. Results: Forty-one patients (9 CD, 13 UC, and 19 Con) were included. After bowel preparation, alpha diversity was lower in the CD group than in the UC ( p = 0.01) and Con ( p = 0.02) groups at timepoint B. Alpha diversity was significantly higher in the UC group than in the CD and Con ( p = 0.03) groups at timepoint C. Beta diversity difference differed between the IBD and Con ( p = 0.001) groups. Based on the differential abundance analysis, the Clostridiales family was increased, whereas the Bifidobacteriaceae family was decreased in CD patients compared to the Con at timepoint B. Conclusions: Bowel preparation may change the fecal microbial composition in IBD patients, which may have a potential role in disease exacerbation after bowel cleansing.

Background: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose‐derived mesenchymal stem cell treatment are contradicting, and real‐world evidence is lacking.Aims: To examine the usability of darvadstrocel therapy in managing perianal CD.Methods: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression.Results: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported.Conclusion: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn’s disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [ p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. Methods: Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. Results: The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. Conclusions: The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.