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Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.

ObjectivesVedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC.MethodsWe performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk.ResultsOur cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness.ConclusionsUST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohns disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12-1.64, P = 2×10-03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18-1.88, P = 9×10-04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07-4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

BACKGROUND: Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated whether microbiome profiles of SR exist in UC. METHODS: Ninety-one UC subjects in clinical and biochemical remission were classified into high and low SR groups by questionnaires. Baseline and longitudinal characterization of the intestinal microbiome was performed by 16S rRNA gene sequencing and fecal and plasma global untargeted metabolomics. Microbe, fecal metabolite, and plasma metabolite abundances were analyzed separately to create random forest classifiers for high SR and biomarker-derived SR scores. RESULTS: High SR reactivity was characterized by altered abundance of fecal microbes, primarily in the Ruminococcaceae and Lachnospiraceae families; fecal metabolites including reduced levels of monoacylglycerols (endocannabinoid-related) and bile acids; and plasma metabolites including increased 4-ethyl phenyl sulfate, 1-arachidonoylglycerol (endocannabinoid), and sphingomyelin. Classifiers generated from baseline microbe, fecal metabolite, and plasma metabolite abundance distinguished high vs low SR with area under the receiver operating characteristic curve of 0.81, 0.83, and 0.91, respectively. Stress reactivity scores derived from these classifiers were significantly associated with flare risk during 6 to 24 months of follow-up, with odds ratios of 3.8, 4.1, and 4.9. Clinical flare and intestinal inflammation did not alter fecal microbial abundances but attenuated fecal and plasma metabolite differences between high and low SR. CONCLUSIONS: High SR in UC is characterized by microbial signatures that predict clinical flare risk, suggesting that the microbiome may contribute to stress-induced UC flares.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

BackgroundUlcerative colitis (UC) and Crohn's disease are 2 types of inflammatory bowel disease (IBD), a group of chronic digestive disorders caused by aberrant immune responses to intestinal microbes. Although changes in the composition of immune cell subsets in the context of IBD have been previously described, the interactions and communication among cells are less well understood. Moreover, the precise mechanisms of action underlying many biologic therapies, including the anti-α4β7 integrin antagonist vedolizumab, remain incompletely understood. Our study aimed to explore possible additional mechanisms through which vedolizumab acts.MethodsWe performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) on peripheral blood and colon immune cells derived from patients with ulcerative colitis treated with the anti-α4β7 integrin antagonist vedolizumab. We applied a previously published computational approach, NicheNet, to predict immune cell-cell interactions, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications (CCC).ResultsWe observed decreased proportions of T helper 17 (TH17) cells in UC patients who responded to vedolizumab and therefore focused the study on identifying cell-cell communications and signals of TH17 cells with other immune cells. For example, we observed that colon TH17 cells from vedolizumab nonresponders were predicted to have a greater degree of interactions with classical monocytes compared with responders, whereas colon TH17 cells from vedolizumab responders exhibited more interactions with myeloid dendritic cells compared with nonresponders.ConclusionsOverall, our results indicate that efforts to elucidate cell-cell communications among immune and nonimmune cell types may increase the mechanistic understanding of current and investigational therapies for IBD.

BACKGROUND: Sex is an integral variable often overlooked in complex disease genetics. Differences between sexes have been reported in natural history, disease complications, and age of onset in inflammatory bowel disease (IBD). While association studies have identified >230 IBD loci, there have been a limited number of studies investigating sex differences underlying these genetic associations. METHODS: We report the first investigation of sex-dimorphic associations via meta-analysis of a sex-stratified association study (34 579 IBD cases, 39 125 controls). In addition, we performed chromosome (chr) X-specific analyses, considering models of X inactivation (XCI) and XCI escape. Demographic and clinical characteristics were also compared between sexes. RESULTS: We identified significant differences between sexes for disease location and perianal complication in Crohns disease and disease extent in ulcerative colitis. We observed genome-wide-significant sex-dimorphic associations (P

The long-term outcome of thiopurine therapy in patients with ulcerative colitis (UC) enrolled in prospective trials have not been evaluated. We aimed to assess the effects of optimised thiopurine maintenance therapy for UC. Long-term data were obtained from patients from our center enrolled in two randomised, prospective, open-label, controlled studies comprising 66 thiopurine-naïve moderate-to-severe patients with UC consisting of a low dose azathioprine (AZA)/allopurinol combination or AZA monotherapy. Following the randomised trials, treatment was adjusted according to adverse effects and metabolites. Patients requiring optimisation initially on AZA monotherapy treatment were switched to low dose AZA in combination with allopurinol, low dose 6-mercaptopurin in combination with allopurinol, or 6-mercaptopurin treatment alone, and those treated with low dose AZA in combination with allopurinol were switched to low dose 6-mercaptopurin in combination with allopurinol or 6-mercaptopurin alone. A total of 62 patients were included in the analysis; 31 were initially treated with AZA monotherapy and 31 with low dose AZA in combination with allopurinol. Initial treatment was tolerated by 67% patients (7 AZA monotherapy and 28 low dose AZA in combination with allopurinol), increasing to 94% (58 patients) post-adjustment. After a median 52-month follow-up period, 38 (93%) out of the 41 primary responding patients-maintained clinical remission without steroids, biologics or surgery. The four intolerant patients and the 17 not responding to optimisation were more likely to require colectomy (odds ratio 16.36; 95% confidence interval 3.08–87.03, p < 0.0001). Optimised thiopurine therapy demonstrated effective long-term treatment for patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum of unknown etiology. Elective appendectomy has been proposed as a possible treatment for patients with refractory ulcerative colitis. Objective: To report the clinical case of a patient with refractory UC who showed improvement in symptomatology and quality of life after undergoing elective appendectomy. Results: We present the case of a 46-year-old patient with a 2-year history of hypothyroidism and ulcerative colitis, with rectal bleeding, abdominal pain, and significant diarrhea despite biological therapy. Elective laparoscopic appendectomy was performed, resulting in symptomatic improvement of the patient as measured by the Inflammatory Bowel Disease Questionnaire. The patient’s preoperative score was 60 points, and the postoperative score was 176. Discussion: It seems evident that ulcerative colitis and the cecal appendix are intimately related. Future challenges should aim to identify clinical characteristics that determine which patients benefit from this intervention. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p

Background & aimsThere are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients.MethodsWe identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis.ResultsWe compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05).ConclusionsIn a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Inflammatory bowel disease, comprising Crohn's disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD.

The article provides information on the pathogenesis, classification and frequency of ophthalmic extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD). A clinical observation of a patient with autoimmune uveitis and IBD is described, demonstrating the importance of early diagnosis of immuno-inflammatory diseases in the implementation of multidisciplinary management of patients with IBD and extraintestinal manidestations. The use of genetically engineered biological drugs helps to control the course of IBD, ophthalmic manifestations and prevents the development of complications.

BACKGROUND: Reducing hospitalization length of stay (LOS) for acute severe ulcerative colitis (ASUC) will reduce healthcare costs, mitigate hospitalization-associated risks (e.g., venous thromboembolism), and improve quality of life. METHODS: A chart review was performed of all adult ASUC-related hospitalizations at University of California, San Francisco, from July 1, 2014, to December 31, 2017. Univariate and multivariate analyses were performed to identify factors associated with LOS

Introduction: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a surgical procedure performed on patients with ulcerative colitis (UC) to avoid the need for permanent stoma. The objective of this study was to assess the quality of life and fecal incontinence in UC patients after IPAA and compare the quality of life among different subgroups. Methods: This cross-sectional study included all UC patients who had underwent IPAA between 2017 and 2021 at Shahid Faghihi Hospital, Shiraz, Iran. Fecal incontinence was evaluated using Wexner questionnaire, while quality of life was assessed using the inflammatory bowel disease questionnaire (IBDQ). Patients were categorized into groups based on the severity of their fecal incontinence, classified as no/mild (0-4) or moderate to severe (≥5), according to their Wexner scores. Differences between groups were assessed using independent sample t-test, Mann--Whitney U, Chi-square, or Fisher's exact tests based on the type of variables. Results: A total of 138 patients completed the Wexner questionnaire, and 119 completed the IBDQ questionnaire. The mean age of participants at the time of questionnaire completion was 43.39 years (±11.16). Among the included patients, 19% experienced moderate to severe fecal incontinence. These patients had lower scores across all domains and the total score of IBDQ compared to patients with no/mild fecal incontinence. Additionally, those who underwent IPAA more than four years ago had significantly lower scores in the social function domain (P=0.047) and total score of IBDQ (P=0.027). Conclusion: Patients with fecal incontinence and those who have undergone IPAA for a longer duration have better quality of life scores. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of Wumei pill on ulcerative colitis (UC) in mice based on the anti oxidative stress pathway of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE). Methods Seventy SPF male C57BL/6 mice were randomly divided into the control group, the UC group, the mesalazine group (MES group, 0.82 g/kg MES), the low dose Wumei pill group (WMW-L group, 5 g/kg crude drug), the middle dose Wumei pill group (WMW-M group, 10 g/kg crude drug), the high dose Wumei pill group (WMW-H group, 20 g/kg crude drug) and the high dose Wumei pills+Nrf2 inhibitor ML-385 group (WMW-H+ML-385 group, Wumei pills crude drug 20 g/kg+20 mg/kg ML-385), with 10 rats in each group. The disease activity index (DAI) score and colonic mucosa injury score were performed in mice after the last administration. Pathological changes of colonic mucosa in mice were observed by HE staining. The levels of interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) and IL-6 in serum and colon tissue of mice were measured by enzyme-linked immunosorbent assay (ELISA). The content of malondialdehyde (MDA) in serum and colon tissue of mice was determined by thiobarbituric acid colorimetry (TBA). The activity of superoxide dismutase (SOD) in serum and colon tissue of mice was measured by xanthine oxidase method. The activity of glutathione peroxidase (GSH-px) in serum and colon tissue of mice was determined by direct method with dithiodinitrobenzoic acid (DTNB). The positive expression of Nrf2 in colon tissue of mice was observed by immunohistochemistry. The expression of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) proteins in colon tissue of mice were detected by Western blot assay. Results Compared with the control group, the DAI score, colonic mucosa injury score, colonic histopathology score, levels of IL-1β, TNF-α, IL6 and MDA in serum and colonic tissue, and expression levels of Nrf2, HO-1 and NQO1 protein in colonic tissue of mice were increased in the UC group, levels of SOD and GSH-px in serum and colon tissue decreased (P＜0.05), the colon mucosa of mice was seriously damaged. Compared with the UC group, changes of corresponding indexes were contrary to the above in the MES group, the WMW-M group and the WMW-H group. However, the expression levels of Nrf2, HO-1 and NQO1 proteins in colon tissue were increased (P＜0.05), and the damage of colon mucosa in mice was alleviated. Changes of the above indexes were dose-dependent in the WMW-L group, the WMW-M group and the WMW-H group. There were no significant differences in the above indexes between the WMW-H group and the MES group. ML-385 attenuated the improvement effect of high dose Wumei pill on colon mucosa injury. Conclusion Wumei pill may alleviate the colon mucosal damage of UC mice by activating Nrf2/ARE antioxidant stress pathway. [ABSTRACT FROM AUTHOR]

Objectives: Inflammatory bowel disease (IBD), generally comprising Crohn's disease (CD) and ulcerative colitis (UC), has become a significant global public health concern in the last decade. This study aimed to determine the alternations in the whole genomic expression profile of patients with IBD in this geographic location for the first time, as there are very few articles in the literature addressing this specific aspect of the field. Methods: The study was conducted in Erbil Governorate in the Kurdistan region of Iraq from July 2021 to July 2022. The genome expression profiles of 10 patients with IBD were compared to their matched controls. The sequences used in the design of the array were selected from GenBank®, dbEST and RefSeq. Whole blood RNA was extracted and hybridisation was conducted on the GeneChip® human genome U133A 2.0 array. The Scanner 3000 was used to scan high-resolution images and the General Comprehensive Operating System was used to read the results. Results: The upregulated genes shared between patients with UC and CD were RIT2, BCL2L1, MDM2 and FKBP8, while the downregulated genes they shared were the NFKBIB, DDX24 and RASA3 genes. Conclusions: Upregulated and downregulated gene expression patterns were detected in individuals with IBD, offering diagnostic potential and opportunities for treatment by targeting the associated pathways. [ABSTRACT FROM AUTHOR]

Background and Aim: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient‐reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. Methods: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1–M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. Results: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. Conclusions: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups. [ABSTRACT FROM AUTHOR]

Background: To describe the frequency and impact of oral lesions and professional dental care costs in patients with inflammatory bowel disease (IBD) (i.e., Crohn disease [CD] or ulcerative colitis [UC]) compared to matched controls). Methods: IBD patients and matched controls were surveyed on general anamnestic information, eating and drinking habits, and oral health‐ and dental care‐related questions; IBD patients were additionally surveyed on oral lesions. Problems related to oral lesions and the amount of money spent for professional dental care in the past 12 months were defined as primary outcome parameters. Results: Answers from 1108 IBD patients and 3429 controls were analyzed. About 30% of the patients indicated having had problems with oral lesions, with CD patients having 46% higher odds and having them more often in a generalized form compared to UC patients. Further, self‐reported severe periodontitis increased the odds of having oral lesions by almost 2.3‐times. However, only about 12.5% of IBD patients were informed by their physician about oral lesions and about 10% indicated receiving treatment for them. Compared to controls, IBD patients required more often dental treatment and spent more money; specifically, UC and CD patients had 27 and 89% higher odds, respectively, for having spent ≥3000 DKK (ca. 440 USD) at the dentist compared to controls. Conclusions: IBD patients have more often oral health problems and higher expenses for professional dental care compared to matched controls. This included problems with IBD‐related oral lesions, but these are rarely addressed by the medical or dental team. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of berberine hydrochloride tablets combined with compound glutamine in treating ulcerative colitis (UC). Methods One hundred and two patients with UC admitted to our hospital were collected and grouped into two groups according to the random number table. Fifty-one patients in the control group were given conventional treatment+compound glutamine, and 51 patients in the experimental group were given berberine hydrochloride tablets based on the control group. Both groups were treated for 8 weeks. The efficacy, modified Mayo score, intestinal mucosal barrier function, soluble late glycation end product receptor (sRAGE), interleukin-17 (IL-17), IL-6 and incidence of untoward reactions were compared between the two groups. Results The total effective rate of the experimental group was higher than that of the control group (92.2% vs. 76.5%, P＜0.05). After treatment, scores of defecation frequency, blood in stool, endoscopic findings, physician's overall evaluation, diamine oxidase (DAO), D-lactic acid, endotoxin, sRAGE, IL-17 and IL-6 were lower in both groups than those before treatment (P＜0.05), and the research group was lower than the control group (P＜0.05). There was no significant difference in the total incidence of untoward reactions between the experimental group and the control group (P＞0.05). Conclusion Berberine hydrochloride tablets combined with compound glutamine are effective in treating UC, which can reduce the activity of UC, improve the intestinal mucosal barrier function, regulate serum sRAGE, IL-17 and IL-6 levels, without increasing adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a long-term inflammatory bowel disease (IBD) caused by abnormal immune responses, leading to inflammation and scarring in the large intestine. The bacteria Prevotella melaninogenica, found in the intestine and mouth, may contribute to UC. This study focuses on the detection of P. melaninogenica in the saliva of UC patients and compares them with the healthy control (HC) group. Methods: The present study was a case-control study including 40 UC patients and 40 healthy controls (HCs) with an average age of 43.0 3± 10.3. This study used a real-time PCR test to investigate the frequency and average number of P. melaninogenica from the 16S rRNA gene sequence of P. melaninogenica in both groups. Results: P. melaninogenica was more frequent in UC patients (77.5%) than HCs (45%) (p = 0.003). The patient group had more bacteria (339.31 ± 1082.29) than HCs (61.29 ± 154.03) (p = 0.005). Women in the UC group had more P. melaninogenica (492.35 ± 1427.61) than the control group (56.98 ± 123.50) (p = 0.0342). Similarly, men in the UC group (262.85 ± 664.97) had more bacteria than the control group (72.62 ± 222.76) (p = 0.015). Conclusion: The current study showed that dysbiosis in P. melaninogenica, a bacterium in human saliva, could be important in the development of UC. Further investigation is needed to evaluate its use as a potential biomarker in the UC.

Background and aimsWe conducted a retrospective cohort study comparing the risk of malignancy between patients treated with vedolizumab vs. tumor necrosis factor-α (TNFα) antagonists in patients with inflammatory bowel diseases (IBD).MethodsUsing an administrative claims database, we identified patients with IBD without prior malignancy who were new users of either vedolizumab or TNFα antagonists between 2014-2018, with no prior exposure to either biologic or in preceding 1 y and had insurance coverage for at least 1 y after treatment initiation. We estimated incidence rate of malignancy (solid organ, hematological or skin cancers) in patients treated with vedolizumab and TNFα antagonists, and compared risk using Cox proportional hazard analysis.ResultsWe included 4807 patients treated with TNFα antagonists (age, 41 ± 15 y, 60% with Crohn's disease [CD]) of whom 65 developed malignancy over 7214 person-year [PY] follow-up (incidence rate [IR], 9.0 per 1000-PY), and 759 patients treated with vedolizumab (age, 46 ± 16y, 42% CD) of whom 11 developed malignancy over 950-PY follow-up (IR, 11.6). No difference was observed in the incidence of malignancy between vedolizumab versus TNFα antagonists (incidence rate ratio, 1.28; 95% CI, 0.61-2.45). After adjusting for age, sex, race, comorbidity burden, disease phenotype and concomitant use of immunomodulators, no difference was observed in time to incident malignancy between vedolizumab versus TNFα antagonists (HR, 1.15; 95% CI, 0.61-2.19). Similar results were observed on stratified analysis by age and concomitant immunomodulators, and after excluding non-melanoma skin cancers.ConclusionsIn an observational study of patients with IBD, no differences were observed in the risk of incident malignancy in patients treated with vedolizumab versus TNFα antagonists.

Background and aimsInflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD).MethodsThrough a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis.ResultsIn patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization.ConclusionApproximately one in five and one in two patients with UC and CD are hospitalized within 5 years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Background and aimsDespite increasing interest in histologic remission as a treatment target in ulcerative colitis (UC), the accuracy of histologic findings in left colon in detecting pancolonic histologic remission is unknown.MethodsIn a retrospective cohort study of patients with endoscopically active pancolitis undergoing treat-to-target interventions, we evaluated the diagnostic accuracy of left-sided (distal to splenic flexure) histologic and endoscopic findings on colonoscopy for detecting histologic and endoscopic healing elsewhere in the colon.ResultsOf 86 patients with moderate to severely active pancolitis who underwent 2 consecutive colonoscopies during treat-to-target interventions, 38% and 51% achieved histologic and endoscopic remission, respectively. Substantial agreement (kappa, 0.67; 95% confidence interval (CI), 0.51-0.83) was observed in histologic findings between left and right colon on follow-up colonoscopy. Histologic, and endoscopic, findings in left colon showed excellent accuracy in detecting pancolonic histologic remission (area under the curve (AUC), 0.96 [95% CI, 0.93-1.0]; misclassification rate, 5.9%), histologic normalization (AUC, 1.0, 0%), endoscopic improvement (AUC, 0.95 [0.96-1.0], 3.5%) and endoscopic remission (AUC, 0.98 [0.96-1.00], 5.8%), respectively.ConclusionsIn patients with active pancolitis undergoing treat-to-target interventions, histologic and endoscopic findings in the left colon on colonoscopy have excellent accuracy for detecting pancolonic histologic remission, histologic normalization, endoscopic improvement, and endoscopic remission. Flexible sigmoidoscopy may suffice for monitoring histologic and endoscopic activity in patients with pancolitis.

Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.

The aim of our case-control study was to identify novel biomarkers of Crohn's disease (CD) that hold the potential to be employed in both disease diagnosis and monitoring activity. In the context of the contribution of intestinal barrier integrity and immune response to the pathogenesis of CD, we assessed the serum concentrations of proguanylin (pro-GN), pentraxin 3 (PTX3) and S100A12 in 20 patients before and after anti-inflammatory treatment, as well as in 20 healthy individuals. Statistical analyses revealed a significant difference in the levels of pro-GN (5.5 vs. 11.35, p < 0.001), PTX3 (2117.9 vs. 1608.37, p < 0.05) and S100A12 (79.4 vs. 19.74, p < 0.001) between pretreatment patients with CD and healthy individuals. Moreover, we noted a significant relationship between the serum profile of PTX3 and disease activity, expressed as CDAI, both before (p < 0.005, r = 0.63) and after (p < 0.05, r = 0.60) treatment. A similar correlation was noted in the case of S100A12 (p < 0.005, r = 0.81), albeit exclusively within the post-treatment group of patients. Anti-inflammatory treatment resulted in an elevation of pro-GN concentration (5.5 vs. 8.04, p < 0.001) and a reduction in PTX3 level (2117.9 vs. 1609.5, p < 0.05) in the serum of patients with CD. In comparison to our previous research conducted on a group of patients with ulcerative colitis (UC), those with CD exhibited reduced levels of PTX3 (2117.9 vs. 3197.05, p < 0.005) and elevated concentrations of S100A12 (79.4 vs. 39.36, p < 0.05). The results obtained from this investigation suggest that measurements of pro-GN, PTX3 and S100A12 could prove beneficial in the diagnosis of Crohn's disease. Assessment of changes in the serum profile of PTX3 appears to be a good marker of response to treatment but also, along with analysis of S100A12 protein serum levels, a useful marker in differentiating CD from UC. [ABSTRACT FROM AUTHOR]

Background/Aims: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). Methods: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. Results: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1 ± 13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P< 0.001), postoperative recurrence (P= 0.001) and high IL-7R expression (P< 0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P< 0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P= 0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P< 0.001), and high C-reactive protein (P< 0.001), OSM (P< 0.04) and OSM-R (P= 0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P= 0.001) on multivariate analysis respectively. Conclusions: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. Methods: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. Results: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. Conclusions: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprises a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract. Onset typically occurs in early adulthood. The incidence of this disease has increased worldwide. Its prevalence has increased in Colombia and occurs predominantly in women. Considering that this disease is not curable, the main objective of management is to achieve remission. Many women are affected by IBD during different stages of their lives, including their reproductive life, pregnancy, and menopause. Because of this, the way the disease is managed in women of reproductive age can affect the course of IBD. Treatment and health maintenance strategies are very relevant; for patients with a desire to conceive, remission of the disease is very important at the time of conception and throughout the pregnancy to ensure adequate outcomes for both mother and fetus. Also, remission is necessary at least 3 months prior to conception. It is well known that active disease during conception and pregnancy is associated with adverse outcomes. In addition, active perianal disease is an indication of cesarean delivery, resulting in an increased risk of intestinal surgery and post-operative complications. [ABSTRACT FROM AUTHOR]

Objective To describe the profile of surgeons who treat patients with inflammatory bowel disease as well as the characteristics of inflammatory bowel disease care, unmet demands, and difficulties.

Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC), N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC  IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.

Background and aimsWe conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD).MethodsUsing an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates.ResultsWe included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn's disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD.ConclusionsIn an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.

Background & aimsWe aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.MethodsA multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.ResultsA total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754).ConclusionsTreatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Background & aimsHyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy.MethodsPre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models.ResultsProteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses.ConclusionsHBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

Background/Aims: Low-volume preparations for colonoscopy are gaining attention for their higher acceptability. However, the efficacy and safety of oral sulfate solution (OSS) preparations in patients with ulcerative colitis (UC) has not been well known. Therefore, we aimed to compare OSS and 2-L polyethylene glycol with ascorbic acid (PEG+Asc) for bowel preparation in inactive UC. Methods: A multicenter, randomized, single-blind study was conducted at six tertiary referral hospitals in Korea. Outpatients with UC who had stable disease activity were randomly allocated to the OSS group or the 2-L PEG+Asc group for bowel preparation before colonoscopy. The study outcomes included treatment efficacy, safety, tolerability, and acceptability. Bowel cleansing was assessed using the Boston Bowel Preparation Scale and rated as successful cleansing if the score was ≥6. Patient acceptance and tolerability were assessed using a 4-point ordinal scale. Additionally, disease activity and laboratory data before and after colonoscopy were evaluated to check for safety. Results: The OSS and 2-L PEG+Asc groups included 92 and 93 participants, respectively. No significant between-group difference was noted in successful cleansing (OSS [96.7%] vs 2-L PEG+Asc [97.8%], p=0.64). Moreover, the safety, acceptance, and tolerability were not significantly different (all p>0.05). Furthermore, no significant changes were found in serum electrolytes or disease activity in either group. Conclusions: OSS is effective for colonoscopy cleansing, has acceptable tolerability, and does not affect disease activity; thus, it can be used safely for bowel preparation in patients with inactive UC.

BackgroundIndigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.MethodsThis open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.ResultsTen of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.ConclusionIN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.Trial registration numberNCT02442960.

Background & aimsWe conducted a systematic review with meta-analysis to estimate rates and trends of colectomy in patients with ulcerative colitis (UC), and of primary and re-resection in patients with Crohn's disease (CD), focusing on contemporary risks.MethodsThrough a systematic review until September 3, 2019, we identified population-based cohort studies that reported patient-level cumulative risk of surgery in patients with UC and CD. We evaluated overall and contemporary risk (after 2000) of surgery and analyzed time trends through mixed-effects meta-regression.ResultsIn patients with UC (26 studies), the overall 1-, 5-, and 10-year risks of colectomy was 4.0% (95% CI, 3.3-5.0), 8.8% (95% CI, 7.7-10.0), and 13.3% (95% CI, 11.3-15.5), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 2.8% (95% CI, 2.0-3.9), 7.0% (95% CI, 5.7-8.6), and 9.6% (95% CI, 6.3-14.2), respectively. In patients with CD (22 studies), the overall 1-, 5-, and 10-year risk of surgery was 18.7% (95% CI, 15.0-23.0), 28.0% (95% CI, 24.0-32.4), and 39.5% (95% CI, 33.3-46.2), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 12.3% (95% CI, 10.8-14.0), 18.0% (95% CI, 15.4-21.0), and 26.2% (95% CI, 23.4-29.4), respectively. In a meta-analysis of 8 studies in patients with CD with prior resection, the cumulative risk of a second resection at 5 and 10 years after the first resection was 17.7% (95% CI, 13.5-22.9) and 31.3% (95% CI, 24.1-39.6), respectively.ConclusionsPatient-level risks of surgery have decreased significantly over time, with a 5-year cumulative risk of surgery of 7.0% in UC and 18.0% in CD in contemporary cohorts. This decrease may be related to early detection and/or better treatment.

Lupus vulgaris (LV) is a chronic, progressive and commonest clinical variant of cutaneous tuberculosis. Among the diverse presentations of LV seen in adults, the ulcerative form is rare explaining the delay in diagnosis. A 30 year old male with non-healing ulcer on trunk for three years with multiple treatments in the past was diagnosed as a case of ulcerative lupus vulgaris after the family history of tuberculosis in two close contacts of patient facilitated the diagnosis, which was further validated by mantoux test and histopathology report. The patient showed immediate response to Antitubercular therapy (ATT) and remained in remission on completion of therapy. Our case highlights that one should consider ulcerative lupus vulgaris as a possible differential diagnosis of non-healing ulcer in patients with personal and/or family history of tuberculosis. [ABSTRACT FROM AUTHOR]

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

Ulcerative colitis (UC) is an autoimmune-mediated colitis which can present in varying degrees of severity and increases the individual's risk of developing colon cancer. While first-line treatment for UC is medical management, surgical treatment may be necessary in up to 25-30% of patients. With an increasing armamentarium of biologic therapies, patients are presenting for surgery much later in their course, and careful understanding of the complex interplay of the disease, its management, and the patient's overall health is necessary when considering he appropriate way in which to address their disease surgically. Surgery is generally a total proctocolectomy either with pelvic pouch reconstruction or permanent ileostomy; however, this may need to be spread across multiple procedures given the complexity of the surgery weighed against the overall state of the patient's health. Minimally invasive surgery, employing either laparoscopic, robotic, or transanal laparoscopic approaches, is currently the preferred approach in the elective setting. There is also some emerging evidence that appendectomy may delay the progression of UC in some individuals. Those who treat these patients surgically must also be familiar with the numerous potential pitfalls of surgical intervention and have plans in place for managing problems such as pouchitis, cuffitis, and anastomotic complications.

BackgroundIt is known that patients with ulcerative colitis (UC) have reduced numbers of short-chain fatty acid (SCFA) producing bacteria and reduced SCFA concentration in feces. There is also evidence that Hispanic patients have increased incidence of UC and increased likelihood of developing disease at a younger age. To understand why this might be, we compared fiber intake and fecal SCFA concentrations in Hispanic children with UC and non-Hispanic children with UC.MethodsIn this cross-sectional study conducted at the Children's Hospital of Los Angeles, stool was collected from 22 Hispanic and 31 non-Hispanic children with UC. SCFAs in the stool were quantified using mass spectrometry. Diet information was collected at the time of stool collection using food frequency questionnaires.ResultsAcetic acid, butyric acid, isovaleric acid, and propionic acid concentrations are significantly lower in Hispanic children with UC compared to age, gender, and disease activity matched non-Hispanic children with UC (p

Abstract Introduction Rosacea and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the skin and the gut, which are interfaces between the environment and the human body. Although growing evidence has implicated a possible link between rosacea and IBD, it remains unclear whether IBD increases the risk of rosacea and vice versa. Therefore, we investigated the association between rosacea and IBD in this study. Methods We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Results Eight eligible studies were included in this meta-analysis. Overall, the prevalence of rosacea was higher in the IBD group than in the control group, with a pooled odds ratio (OR) of 1.86 (95% confidence interval [CI](1), 1.52–2.26). Both the Crohn’s disease and the ulcerative colitis groups had higher prevalences of rosacea than the control group, with ORs of 1.74 (95% CI 1.34–2.28) and 2.00 (95% CI 1.63–2.45), respectively. Compared with those in the control group, the risks of IBD, Crohn’s disease, and ulcerative colitis were significantly higher in the rosacea group, with incidence rate ratios of 1.37 (95% CI 1.22–1.53), 1.60 (95% CI 1.33–1.92), and 1.26 (95% CI 1.09–1.45), respectively. Conclusion Our meta-analysis suggests that IBD is bidirectionally associated with rosacea. Future interdisciplinary studies are needed to better understand the mechanism of interaction between rosacea and IBD .