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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.

Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia-inducible factor one-alpha (HIF-1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self-assembly of PEG-DPCA conjugates. Pre-treatment of mice with PEG-DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)-induced colitis. Surprisingly, a single subcutaneous dose of PEG-DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA-induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF-1α and associated targets leading to an epithelial-to-mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand-alone restorative treatment to combat active IBD is warranted.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.

INTRODUCTION: Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. MATERIAL AND METHODS: We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. RESULTS: Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. CONCLUSIONS: HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

BACKGROUND & AIMS: Intestinal inflammation is associated with loss of enteric cholinergic neurons. Given the systemic anti-inflammatory role of cholinergic innervation, we hypothesized that enteric cholinergic neurons similarly possess anti-inflammatory properties and may represent a novel target to treat inflammatory bowel disease. METHODS: Mice were fed 2.5% dextran sodium sulfate (DSS) for 7 days to induce colitis. Cholinergic enteric neurons, which express choline acetyltransferase (ChAT), were focally ablated in the midcolon of ChAT::Cre;R26-iDTR mice by local injection of diphtheria toxin before colitis induction. Activation of enteric cholinergic neurons was achieved using ChAT::Cre;R26-ChR2 mice, in which ChAT+ neurons express channelrhodopsin-2, with daily blue light stimulation delivered via an intracolonic probe during the 7 days of DSS treatment. Colitis severity, ENS structure, and smooth muscle contractility were assessed by histology, immunohistochemistry, quantitative polymerase chain reaction, organ bath, and electromyography. In vitro studies assessed the anti-inflammatory role of enteric cholinergic neurons on cultured muscularis macrophages. RESULTS: Ablation of ChAT+ neurons in DSS-treated mice exacerbated colitis, as measured by weight loss, colon shortening, histologic inflammation, and CD45+ cell infiltration, and led to colonic dysmotility. Conversely, optogenetic activation of enteric cholinergic neurons improved colitis, preserved smooth muscle contractility, protected against loss of cholinergic neurons, and reduced proinflammatory cytokine production. Both acetylcholine and optogenetic cholinergic neuron activation in vitro reduced proinflammatory cytokine expression in lipopolysaccharide-stimulated muscularis macrophages. CONCLUSIONS: These findings show that enteric cholinergic neurons have an anti-inflammatory role in the colon and should be explored as a potential inflammatory bowel disease treatment.

Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs' profile in a mouse CAC model. Further, gut macrophage-intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines' secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages' recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Background & aimsChronic inflammatory illnesses are debilitating and recurrent conditions associated with significant comorbidities, including an increased risk of developing cancer. Extensive tissue remodeling is a hallmark of such illnesses, and is both a consequence and a mediator of disease progression. Despite previous characterization of epithelial and stromal remodeling during inflammatory bowel disease, a complete understanding of its impact on disease progression is lacking.MethodsA comprehensive proteomic pipeline using data-independent acquisition was applied to decellularized colon samples from the Muc2 knockout (Muc2KO) mouse model of colitis for an in-depth characterization of extracellular matrix remodeling. Unique proteomic profiles of the matrisomal landscape were extracted from prepathologic and overt colitis. Integration of proteomics and transcriptomics data sets extracted from the same murine model produced network maps describing the orchestrating role of matrisomal proteins in tissue remodeling during the progression of colitis.ResultsThe in-depth proteomic workflow used here allowed the addition of 34 proteins to the known colon matrisomal signature. Protein signatures of prepathologic and pathologic colitic states were extracted, differentiating the 2 states by expression of small leucine-rich proteoglycans. We outlined the role of this class and other matrisomal proteins in tissue remodeling during colitis, as well as the potential for coordinated regulation of cell types by matrisomal ligands.ConclusionsOur work highlights a central role for matrisomal proteins in tissue remodeling during colitis and defines orchestrating nodes that can be exploited in the selection of therapeutic targets.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.

Microbial sensors play an essential role in maintaining cellular homoeostasis. Our knowledge is limited on how microbial sensing helps in differential immune response and its link to inflammatory diseases. Recently we have confirmed that ELMO1 (Engulfment and Cell Motility Protein-1) present in cytosol is involved in pathogen sensing, engulfment, and intestinal inflammation. Here, we show that ELMO1 interacts with another sensor, NOD2 (Nucleotide-binding oligomerization domain-containing protein 2), that recognizes bacterial cell wall component muramyl dipeptide (MDP). The polymorphism of NOD2 is linked to Crohn's disease (CD) pathogenesis. Interestingly, we found that overexpression of ELMO1 and mutant NOD2 (L1007fs) were not able to clear the CD-associated adherent invasive E. coli (AIEC-LF82). The functional implications of ELMO1-NOD2 interaction in epithelial cells were evaluated by using enteroid-derived monolayers (EDMs) from ELMO1 and NOD2 KO mice. Subsequently we also assessed the immune response in J774 macrophages depleted of either ELMO1 or NOD2 or both. The infection of murine EDMs with AIEC-LF82 showed higher bacterial load in ELMO1-KO, NOD2 KO EDMs, and ELMO1 KO EDMs treated with NOD2 inhibitors. The murine macrophage cells showed that the downregulation of ELMO1 and NOD2 is associated with impaired bacterial clearance that is linked to reduce pro-inflammatory cytokines and reactive oxygen species. Our results indicated that the crosstalk between microbial sensors in enteric infection and inflammatory diseases impacts the fate of the bacterial load and disease pathogenesis.

Chronic inflammatory enteropathy (CIE) and low-grade intestinal T-cell lymphoma (LGITL) are common chronic enteropathies (CE) in cats. Enteric microbiota dysbiosis is implicated in the pathogenesis of CE; however, the mechanisms of host-microbiome interactions are poorly understood in cats. Microbial indole catabolites of tryptophan (MICT) are gut bacterial catabolites of tryptophan that are hypothesized to regulate intestinal inflammation and mucosal barrier function. MICTs are decreased in the sera of humans with inflammatory bowel disease and previous studies identified altered tryptophan metabolism in cats with CE. We sought to determine whether MICTs were decreased in cats with CE using archived serum samples from cats with CIE (n = 44) or LGITL (n = 31) and healthy controls (n = 26). Quantitative LC-MS/MS was used to measure serum concentrations of tryptophan, its endogenous catabolites (kynurenine, kynurenate, serotonin) and MICTs (indolepyruvate, indolealdehyde, indoleacrylate, indoleacetamide, indoleacetate, indolelactate, indolepropionate, tryptamine). Serum concentrations of tryptophan, indolepropionate, indoleacrylate, indolealdehyde, indolepyruvate, indolelactate were significantly decreased in the CIE and LGITL groups compared to those in healthy controls. Indolelactate concentrations were significantly lower in cats with LGITL compared to CIE (p = 0.006). Significant correlations were detected among serum MICTs and cobalamin, folate, fPLI, and fTLI. Our findings suggest that MICTs are promising biomarkers to investigate the role of gut bacteria in the pathobiology of chronic enteropathies in cats.

Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals. [ABSTRACT FROM AUTHOR]

In addition to facilitating lipid digestions, bile acids (BA) are signalling molecules acting on receptors on immune cells and along the gastrointestinal (GI) tract. The aim of this study was to assess if altered bile acid profiles in plasma are associated with Crohn's disease (CD). This cross-sectional study included individuals (aged ≥18 years) referred for colonoscopy at a tertiary centre in Stockholm between 2016 and 2019. All participants received bowel preparation, completed a lifestyle questionnaire and provided blood samples for analysis. During colonoscopy, severity of disease was graded, and biopsies were taken from colonic mucosa. In the current substudy, 88 individuals with CD and 88 age-matched controls were selected for analysis of BA in plasma with ultra performance liquid chromatography (UPLC). Linear regression models were then used to compare mean bile acid concentrations and concentration ratios between CD and controls. Individuals with CD had lower plasma concentrations of the majority of secondary BA compared to controls, in total CD/CC ratio 0.60 (SE 0.12), p = 0.001. The most prominent observations were lower levels of deoxycolic acid derivates and lithocolic acid derivates among participants with CD. Moreover, plasma concentration for secondary BA among participants with active CD was significantly lower compared to those with CD in remission, CD active/CD remission ratio 0.65 (SE 0.11), p < 0.002. Crohn's disease may be associated with altered plasma bile acid composition. The significance of colonic bacterial diversity in this context needs to be investigated in further studies. It is known that Crohn's disease is associated with dysbiosis in the gut microbiota and that primary bile acids are transformed to secondary bile acids by bacterial enzymes in the gut before reabsorbed and transported back to the liver. In this cross-sectional study, Crohn's disease was associated with lower concentrations of secondary bile acids in blood plasma The findings should encourage further studies the role of the gut microbiome and bile acid metabolism in development of Crohn's disease and bile acid profile as a biomarker for bowel inflammation. [ABSTRACT FROM AUTHOR]

The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population's age- and sex-specific cancer incidence rates, retrievable from NORDCAN. The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50–59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02–2.99) as did UC patients diagnosed with IBD at 50–59 (SIR 2.1; 95% CI, 1.10–3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable. [ABSTRACT FROM AUTHOR]

Background: Dietary recommendations in inflammatory bowel disease (IBD) are inconclusive, and patients may follow restrictive diets with increased risk of malnutrition. The aim of this study was to compare dietary intakes and nutritional status in men and women with newly diagnosed IBD with a general population sample, and to investigate whether intakes were in line with the Nordic Nutrition Recommendations. Methods: This was a cross-sectional study including adults≥ 40 years with IBD from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III cohort study. A validated food frequency questionnaire (FFQ) was used in dietary data collection, and a sample from the seventh survey of the Tromsø Study was included as a comparison group. Results: A total of 227 men and women with IBD were included. IBD patients had higher intake of grain products, sweetened beverages, energy, fat and polyunsaturated fat (PUFA), but lower intake of dairy products, alcohol and iodine compared to adults from the comparison sample (p < 0.01). Intakes of saturated fat and carbohydrates in both genders, and vitamin D in women were not within recommended levels. Anemia and hypoalbuminemia were more prevalent in IBD patients than in the comparison sample. Conclusions: Dietary intakes in newly diagnosed IBD patients were mostly in line with Nordic Nutrition Recommendations. Higher proportion of IBD patients exceeded recommended allowances of fat and added sugar than the comparison sample. Insufficient micronutrient intake, anemia and hypoalbuminemia are present challenges in IBD patients that require monitoring. Self-prescribed dietary restrictions in patients with inflammatory bowel disease (IBD) due to inconclusive dietary guidance may influence their risk of malnutrition. Comprehensive assessment of both dietary intake and nutritional status as early as time of diagnosis may help identify challenges in this patient group and implement appropriate interventions. [ABSTRACT FROM AUTHOR]

Background: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). Methods: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. Results: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. Conclusions: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise. [ABSTRACT FROM AUTHOR]

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection. Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study. Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test. Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to explore the causal association between inflammatory bowel disease (IBD) and the risk of type 2 diabetes (T2D) based on a two-sample Mendelian randomization (MR) study. Methods: Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published two genome-wide association studies (GWAS) including SNPs related to IBD, UC, or CD in European participants (n = 71,997) and East Asian participants (n = 16,805). Two GWAS including SNPs associated with T2D included 655,666 Europeans and 433,540 East Asians. A series of screening processes were performed to select qualified instrumental SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the MR-Egger regression, and the weighted median to estimate the causal effects of IBD, ulcerative colitis (UC) or Crohn' disease (CD) on T2D. Cochran's Q test was conducted to evaluate the statistical heterogeneity between SNPs in the IVW method. The leave-one-out analysis was employed to assess whether the results were caused by any single SNP associated with IBD, UC, or CD. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Results: The IVW results demonstrated that IBD could increase the risk of T2D in the European population (OR = 1.0230, 95%CI: 1.0073–1.0390). UC was positively associated with the risk of T2D according to the weighted median (OR = 1.0274, 95%CI: 1.0009–1.0546) and IVW (OR = 1.0244, 95%CI: 1.0071–1.0421) results in the European population. The IVW results indicated that the CD was positively associated with the risk of T2D in the European population (OR = 1.0187, 95%CI: 1.0045–1.0330). In the East Asian population, there are no associations between the IBD, UC, or CD and the risk of T2D (all P > 0.05). MVMR results revealed that the causal effect UC on T2D was still statistically significant after including body mass index (BMI) or low-density lipoprotein (LDL). Conclusion: IBD, UC, or CD had causal effects on the risk of T2D in the European population, which might provide evidence for the prevention of T2D in patients with IBD, UC, or CD. [ABSTRACT FROM AUTHOR]

Purpose: Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. Background: Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. Methods: A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. Results: 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P =.01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3 days, P =.04). Conclusion: Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage. [ABSTRACT FROM AUTHOR]

The establishment of an interdisciplinary Inflammatory Bowel Disease (IBD) center is associated with improved healthcare utilization, according to a study published in the European Journal of Clinical Investigation. The study found that after the institution of the IBD center, hospitalizations per patient per year decreased, the number of patients on biologics increased, and there was an improvement in the total number of hospitalizations and length of hospital stay. The findings suggest that the coordinated collaboration of healthcare professionals and the implementation of specialized services can lead to better patient care and outcomes in IBD management. [Extracted from the article]

Previous study has demonstrated that the Dietary Inflammation Index (DII) played a role in the risk of inflammatory bowel disease (IBD), however, the prevalence and risk factors for IBD are distinct across locations and groups, and therefore, the findings are debatable and warrant further investigation. A total of 4363 participants were calculated in the National Health and Nutrition Examination Survey (NHANES) 2009 to 2010, of whom 1.21% self‐reported a history of IBD. DII values were performed as a good predictor of dietary inflammation based on data from two 24‐h dietary reviews in the NHANES database. Comparing the multifarious effects along with variations of the whole population by grouping populations according to DII quartiles, dietary inflammation levels increased progressively from DII quartile 1(Q1) to quartile 4(Q4). The association between DII and IBD was tested with multi‐variable logistic regression models, subgroup analyses and weighted generalized additive models. Participants in the Q4 group showed the highest levels of C‐reactive protein and reduced haemoglobin and albumin levels. Logistic regression confirmed the odds ratios (95% confidence intervals) of IBD for DII were 0.99 (0.86, 1.15), 0.97 (0.84, 1.13) and 0.80 (0.66, 0.98) in models 1, 2 and 3, respectively. The negative correlation between DII and IBD among United States adults from the NHANES database became increasingly apparent as covariates were adjusted. Subgroup analyses and smoothed curve fitting confirmed the inverse results. The study revealed that DII was correlated with the overall physical well‐being of participants. However, there was no significant association between DII and IBD. [ABSTRACT FROM AUTHOR]

Purpose: Uveitis is one of the ocular manifestations of inflammatory bowel disease (IBD) that is often overlooked and has been considered a sign of severe IBD. As typical subtypes of IBD, differences exist in the prevalence of uveitis between Crohn's disease (CD) and ulcerative colitis (UC). Our study systematically assessed differences in the prevalence of uveitis between CD and UC. Methods: The Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines were used. We performed a systematic review of published literature from PubMed and Embase on 30 March 2022. Two investigators independently selected studies, extracted data and evaluated methodological quality. Either a fixed‐ or a random‐effects model was used to calculate the risk ratio (RR), odds ratio (OR) and 95% confidence interval (95% CI) depending on the heterogeneity of studies. Sensitivity analysis was used to examine the heterogeneity by removing article by article, while subgroup analysis was conducted in accordance with various regions. Results: Our study included data from 14 studies encompassing 115 854 participants. The prevalence of uveitis in IBD was estimated to be 2.38% (95% CI 1.60%–3.17%). The prevalence of uveitis in CD (3.27%, 95% CI 2.15%–4.39%) was significantly higher than in UC (1.60%, 95% CI 0.93%–2.27%; RR 1.76, 95% CI 1.39–2.22, p < 0.05). In subgroup analysis, a higher incidence of CD combined with uveitis was also observed in IBD patients residing in Europe (RR 1.75, 95% CI 1.37–2.24). Conclusions: Data from 115 854 IBD patients showed that CD patients were more likely to suffer from uveitis than UC patients. Ocular manifestations in IBD, particularly CD, warrant greater attention. [ABSTRACT FROM AUTHOR]

Introduction: Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy. Methods: This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed. Results: At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period 2013–2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678 euro (€), for UC and €6925 for CD. Conclusion: This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers. Plain Language Summary: Data from clinical practice can be used to guide healthcare decisions and optimise treatment for patients with ulcerative colitis and Crohn's disease. This study used anonymised patient information from almost four million individuals across Italy to describe the epidemiology, patient characteristics, treatment patterns and healthcare costs of patients with ulcerative colitis and Crohn's disease. Adults with an Italian National Health System code in their records associated with the diagnosis of ulcerative colitis or Crohn's disease were included. Baseline characteristics were balanced between groups and rates of perceived incidence were numerically similar to the results reported in similar Italian studies. This study found that patients with ulcerative colitis and Crohn's disease were most often prescribed conventional treatments, and biological treatments were least-commonly prescribed. More than half of patients with ulcerative colitis and nearly half of those with Crohn's disease were persistent with first (index) treatment of mesalazine and topical corticosteroids and with biologic index treatment during the follow-up period. Switch occurred in up to approximately a quarter of patients with ulcerative colitis and Crohn's disease. The main factors that predicted switch were index biologic for ulcerative colitis and baseline comorbidities for Crohn's disease. The average direct cost per patient in 1 year was 7678 euro (€) for ulcerative colitis and €6925 for Crohn's disease. The results of this analysis may help to optimise therapy for patients with ulcerative colitis and Crohn's disease, and to inform decision-makers in healthcare systems on which treatment options provide value for money and benefit patients. [ABSTRACT FROM AUTHOR]

Sclerosing cholangitis recurs in some patients following liver transplantation. These high-risk patients may provide clues to the pathogenesis of this disease. Aims: In this single-center study, from a high prevalence area, we investigated the incidence of recurrent sclerosing cholangitis following liver transplantation and re-transplantation. Methods: A retrospective cohort study of all patients with primary sclerosing cholangitis transplanted in the Irish National Liver Transplant program between 1993 and 2019. Results: Recurrent sclerosing cholangitis occurred in 23/112 patients (20.7%). Overall patient survival was similar in the recurrence and non-recurrence groups. Nine patients were re-transplanted for recurrent disease. Patients with recurrence were significantly younger (42.7 + − 2.5 years vs. 49.3 + − 1.3 p < 0.05), and colectomy post-transplant was performed more frequently in the recurrence group (6/21 vs. 9/81 p < 0.05). Further recurrence after re-transplantation was identified in 6/9 patients and was identified a shorter time after transplant than the first recurrence (median 41.5 months; range 26–53 vs. median 65.5; range 38: p < 0.05). Discussion/conclusion: Recurrent PSC following liver transplantation is common, particularly in younger patients. It occurs earlier and is more frequent following a second transplant. [ABSTRACT FROM AUTHOR]

A 37-year-old woman developed severe colitis with diffuse mucosal erythema and ulcerations throughout the entire colon after the 3rd vaccination of COVID-19. Stool culture was negative, and the pathological findings showed increased lymphoplasmacytic and neutrophilic infiltration in the colonic lamina propria, which were consistent with ulcerative colitis. After the treatment with anti-tumor necrosis factor-α agent, the ulceration markedly improved with development of severe colonic stenosis, which was successfully dilated with endoscopic balloon dilation. In case of COVID-19 vaccination, it should be noted that vaccination could be a trigger for the onset of UC. [ABSTRACT FROM AUTHOR]

Intestinal fibrosis is a common complication of inflammatory bowel disease and is characterized by tissue stiffening and luminal narrowing. Dihydromyricetin (DHM) can alleviate liver fibrosis and renal interstitial fibrosis by inducing autophagy. However, whether DHM can alleviate intestinal fibrosis remains unclear. This study is aimed at evaluating the role and mechanism of action of DHM in inflammatory bowel disease-associated intestinal fibrosis. Mice were administered dextran sulfate sodium (DSS) in drinking water to induce inflammatory bowel disease-associated intestinal fibrosis. HE staining, qPCR, and Western blotting were used to analyze colon inflammation. Masson's trichrome staining, qPCR, Western blotting, and immunofluorescence staining were used to evaluate the severity of fibrosis. Transmission electron microscopy and Western blotting were used to assess the activation of autophagosomes. The human colonic fibroblast line CCD-18Co was cultured in the presence of TGF-β1 to develop a fibrotic phenotype. Immunofluorescence staining, Western blotting, and qPCR were used to assess the alteration of fibrosis markers and used to investigate whether DHM-induced autophagy was involved in the inactivation of CCD-18Co cells. Additionally, the role of the PI3K/AKT/mTOR pathway was investigated. DHM alleviated intestinal inflammation and inhibited the progression of intestinal fibrosis. Additionally, DHM induced the activation of autophagy, thereby alleviating intestinal fibrosis, and downregulated the PI3K/AKT/mTOR signaling pathway in vitro. Overall, this study demonstrated that DHM can inhibit the progression of intestinal fibrosis and activation of colonic fibroblasts by inducing autophagy through the PI3K/AKT/mTOR signaling pathway, thereby playing a preventive and therapeutic role in intestinal fibrosis. [ABSTRACT FROM AUTHOR]

Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAI), and ELIAKIM. Recent advances in artificial intelligence (AI) have made it possible to automatically select the most relevant frames in CE. Objectives: In this proof-of-concept study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation. Design: Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAI, and ELIAKIM scores were calculated. Methods: We developed a convolutional neural network-based automated score consisting of the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence-generated score (AIS). Results: A total of 61 patients were included. The median LS was 225 (0–6006), CECDAI was 6 (0–33), ELIAKIM was 4 (0–38), and SB_AIS was 0.5659 (0–29.45). We found a strong correlation between SB_AIS and LS, CECDAI, and ELIAKIM scores (Spearman's r = 0.751, r = 0.707, r = 0.655, p = 0.001). We found a strong correlation between LS and ELIAKIM (r = 0.768, p = 0.001) and a very strong correlation between CECDAI and LS (r = 0.854, p = 0.001) and CECDAI and ELIAKIM scores (r = 0.827, p = 0.001). Conclusion: Our study showed that the AI-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining of a CE score that may accurately correlate with prognostic factors and aid in the management and treatment of CD patients. Plain language summary: Artificial intelligence in Crohn's disease: the development of an automated score for disease activity evaluation This study introduces an innovative AI-based approach to evaluate Crohn's Disease. The AI system automatically analyzes images from capsule endoscopy, focusing on finding ulcers and erosions to measure disease activity. The research reveals a robust correlation between the AI-generated score assessing inflammation in the small bowel and traditional clinical scores. This suggests that the AI solution could be a quicker and more consistent way to evaluate Crohn's Disease, speeding up the evaluation process and reducing manual scoring variability. While promising, the study acknowledges limitations and emphasizes the need for further validation with larger groups of patients. Overall, it represents a crucial step toward integrating AI into gastroenterology, offering a glimpse into a future of more objective and personalized Crohn's Disease evaluation. [ABSTRACT FROM AUTHOR]

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic and unspecific inflammatory disorder of the gastrointestinal tract, and current treatment options often fail to maintain long‐term remission. Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate‐producing probiotic (EcNP3) to achieve sustained restoration of propionate levels in the gut and increase its bioavailability. DSS‐induced experimental intestinal inflammation model was used to evaluate the effect of EcNP3 on improving the intestinal mucosal barrier and increasing the proportion of anti‐inflammatory macrophages. It was found that EcNP3 exhibited a restorative effect on the depletion of peritoneal anti‐inflammatory macrophages (F4/80hiCD11bhi) and significantly improved the expression level of IL‐10. Simultaneously, the expression of IL‐1β, IL‐6, and CXCL1 was downregulated while inhibiting apoptosis of tissue‐resident macrophages ex vivo. Further investigation revealed that EcNP3 regulates IL‐10 expression through G protein‐coupled receptor 43 and histone deacetylase. Furthermore, EcNP3 significantly inhibited the protein expression of HDAC1 and promoted the histone acetylation level of cells. Finally, EcNP3 significantly improved DSS‐induced colitis in mice by increasing mucus production and reducing inflammatory infiltration. Our results suggest that the engineered live biotherapeutic product EcNP3 is a safe and potently efficacious treatment for IBD, which defines a novel strategy in IBD therapy through macrophage IL‐10 signaling. [ABSTRACT FROM AUTHOR]

Background: Providing relevant digital health information of high quality may promote treatment adherence and self-management for patients with inflammatory bowel disease. The development of digital health services is optimised by considering end users' needs. Aim: To identify key aspects required for digital promotion of inflammatory bowel disease patients' self-management by exploring their health information needs and the preferences of both patients and healthcare professionals in relation to the digital provision of inflammatory bowel disease health services. Methods: Data from an audit of 1,481 electronic health record summaries from an inflammatory bowel disease help line, 17 semi-structured interviews with inflammatory bowel disease patients and 2 focus group interviews with 11 healthcare professionals were analysed. Results: Patients primarily contacted the hospital due to concerns about symptoms, examinations and tests, and medicines. Their concerns appeared to vary according to diagnosis, gender, age and disease duration. The interviews identified two overarching themes: (1) the available health information and patients' health information needs, and (2) whishes, thoughts and preferences for a digital solution in IBD care with relevant and individualised information. Conclusions: The findings delineate key aspects for developing a suitable digital health information service. Patients seek information from healthcare professionals about treatment; however, in a digital solution, they want access to relevant and practical information about the disease, treatment and self-management. Both patients and healthcare professionals saw opportunities for increasing health data availability to patients. However, healthcare professionals expressed concerns about adapting, maintaining and ensuring the relevance of patient health information without increasing their workload and, thus, reducing quality of care. [ABSTRACT FROM AUTHOR]

Background: Inflammation and oxidative stress play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aimed to explore the effects of copper chaperone Antioxidant-1 (Atox1) on macrophages in a mouse model of intestinal inflammation. Methods: A mouse model of TNBS-induced colitis was established and verified using the disease activity index. Atox1 conditional knockout mice were applied. The proportion of macrophages in colonic lamina propria mononuclear cells and ROS production were analyzed using flow cytometry. Inflammatory cytokines were measured using ELISA. Expression of macrophage M1/M2 polarization markers, p47phox, NLRP3, and Caspase-1 p20 was measured using quantitative RT-PCR and Western blotting. Results: Atox1 expression was up-regulated in colon tissues of TNBS-induced colitis mice. Macrophages isolated from TNBS-induced colitis mice showed M1 polarization and nuclear translocation of Atox1. Inhibiting copper chaperone activity decreased p47phox, ROS production, and M1 polarization induced by CuCl2 in macrophages. TNBS induced up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression in mice, an effect which was preempted by Atox1 knockout. Inflammatory cytokines and expression of M1 polarization markers, p47phox, NLRP3, Caspase-1 p20 were also increased in macrophages isolated from TNBS-induced colitis mice. These changes were alleviated in mice with Atox1 knockout. The effects of Atox1 on macrophage polarization were mediated via the ROS-NLRP3 inflammasome pathway. Conclusion: Atox1 plays a pro-inflammatory role, promotes M1 polarization of macrophages, and increases the concentrations of pro-inflammatory cytokines in intestinal tissue by regulating the ROS-NLRP3 inflammasome pathway. Atox1 is a potential therapeutic target in IBD. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) consists of two main types: Crohn's disease (CD) and ulcerative colitis (UC). The epidemiology of IBD patients has not been comprehensively studied in EMRO countries; therefore, we conducted this meta-analysis to study the epidemiology of this disease in these countries. Methods: We searched four international databases, namely Scopus, Web of Knowledge (ISI), Medline/PubMed, and ProQuest, from inception up to the end of May 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline was used to carry out this systematic review and meta-analysis investigation. Using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist, the quality of the selected papers was assessed. Results: Based on the results of this study, the incidence of UC in EMRO countries was 2.65 per 100,000 (95% CI: 1.39–3.90), and the incidence of CD was 1.16 per 100,000 (95% CI: 0.73–1.59). The most commonly involved intestinal segment in CD was the terminal ileum (44.7%, 95% CI: 34.7–55.2), followed by the ileum (29.8%, 95% CI: 22.2–38.6), and colon (18.7%, 95% CI: 10.8–30.4). However, in UC patients, extensive colitis was the most common finding (32.3%, 95% CI: 26.4–38.8), followed by proctosigmoiditis (27.9%, 95% CI: 21.1–35.8), left-sided colitis (27.4%, 95% CI: 22.7–32.7), and proctitis (22.6%, 95% CI: 17.5–28.5). Conclusion: As a result, we were able to establish the traits of IBD patients in EMRO nations. UC patients had a higher incidence than CD patients. The most common regions of involvement in CD and UC patients, respectively, were the colon and pancolitis. Compared to UC patients, CD patients had a higher history of appendectomy. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of conventional US (ultrasound), SMI (superb microvascular imaging), and CEUS (contrast-enhanced ultrasound) features for the assessment of the activity of inflammatory bowel disease.Conventional US, CEUS and SMI features of 76 patients were retrospectively analyzed. Patients were categorized into two groups: active group (n = 57) and inactive group (n = 19), with endoscopic results as reference standard. Results in the active group and inactive group were compared using an independent t-test, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve (ROC) analysis. Cut-off values were determined using ROC analysis, and sensitivity and specificity were calculated. US quantitative and TIC-based quantitative parameters were analyzed, and each patient was scored based on the parameters that are statistically significant and immediately available in the clinic to evaluate the diagnostic ability of conventional US, SMI, and CEUS features for active IBD patients.Qualitative parameters such as CEUS enhancement pattern I/II, LimbergIII/IV, and lost bowel stratification were reliable indicators of active patients. Quantitative parameters such as bowel thickness and VI of mSMI were reliable indicators of active patients. Patients scored based on these statistically significant parameters with a score ≥3, were highly suspected to be active patients. For TIC-based quantitative parameters, PE, WiAUC, WoAUC, WiWoAUC, WiR, WiPI, and WoR were statistically significant in the differentiation of active IBD from inactive IBD.Conventional US, SMI, and CEUS features may help in the differentiation of active IBD from inactive IBD and have potential application value in the choice of treatment options. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD) is a chronic disease involving multiple genes, and the current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. MiR-146a plays a pivotal role in repression of innate immunity, but its function in the intestinal inflammation is sort of controversy, and the genetic regulatory networks regulated by miR-146a in IBD has not been revealed. Methods: RT-qPCR was employed to detect the expression of miR-146a in IBD patients and in a mouse IBD model induced by dextran sulfate sodium (DSS), and then we generated a miR-146a knock-out mouse line with C57/Bl6N background. The disease activity index was scored in DSS-treated miR-146a deficiency mice and their wild type (WT) littermates. Bulk RNA-sequencing, RTqPCR and immunostaining were done to illustrate the downstream genetic regulatory networks of miR-146a in flamed colon. Finally, the modified miR-146a mimics were used to treat DSS-induced IBD in miR-146a knock-out and WT IBD mice. Results: We showed that the expression of miR-146a in the colon was elevated in dextran sulfate sodium (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and more significant rectal bleeding, shorter colon length, and colitis in miR-146a knock-out mice than WT mice. The miR-146a mimics alleviated DSS-induced symptoms in both miR-146a-/- and WT mice. Further RNA sequencing illustrated that the deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes that cover multiple genetic regulatory networks in IBD, and supplementation with miR-146a mimics inhibited the expression of many IBD-related genes. Quantitative RT-PCR or immunostaining confirmed that Ccl3, Saa3, Csf3, Lcn2, Serpine1, Serpine2, MMP3, MMP8, MMP10, IL1A, IL1B, IL6, CXCL2, CXCL3, S100A8, S100A9, TRAF6, P65, p-P65, and IRAK1 were regulated by miR-146a in DSS induced IBD. Among them, MMP3, MMP10, IL6, IL1B, S100A8, S100A9, SERPINE1, CSF3, and IL1A were involved in the active stage of IBD in humans. Discussion: Our date demonstrated that miR-146a acts as a top regulator in C57/BL6N mice to systematically repress multiple genetic regulatory networks involved in immune response of intestine to environment factors, and combinatory treatment with miR-146a-5p and miR-146a-3p mimics attenuates DSS-induced IBD in mice through down-regulating multiple genetic regulatory networks which were increased in colon tissue from IBD patients. Our findings suggests that miR-146a is a top inhibitor of IBD, and that miR-146a-5p and miR-146a-3p mimics might be potential drug for IBD. [ABSTRACT FROM AUTHOR]

Background: Metastatic Crohn's disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF). Case presentation: We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn's disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient. For our study more than 1600 publications were screened for cases of metastatic Crohn's disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review. Conclusion: The successful ustekinumab treatment of a patient with metastatic Crohn's disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases. [ABSTRACT FROM AUTHOR]

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction. Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran's Q statistic was utilized to detect the heterogeneity. Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02-1.21, p = 0.019), and also the genetically determined Crohn's disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02-1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92-1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity. Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn's disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: This study tested the acceptability and efficacy of an Acceptance and Commitment Therapy and compassion-based intervention (LIFEwithIBD) in people with IBD through a two-arm RCT. Methods: Participants were recruited at the Gastroenterology Department of the Coimbra University Hospital between June and September 2019. Of the 355 patients screened, those who accepted to participate were randomly assigned to one of two conditions: experimental group (LIFEwithIBD; n = 25) or control group (waitlist; n = 29). Participants completed self-report measures at baseline (T0), post-intervention (T1), and 3-month (T2) and 12-month (T3) follow-ups. Intervention acceptability was assessed. Efficacy was examined using intent-to-treat ANCOVA at post-intervention after adjusting for baseline values of depressive, anxiety, and stress symptoms (primary outcomes). Linear mixed models for all longitudinal outcomes were also analysed. Inflammatory and disease biomarkers were determined at T0 and T3. Results: Acceptability results revealed a high level of satisfaction and perceived usefulness regarding the intervention. Both groups experienced a significant decrease in stress symptoms and IBD symptom perception at T1. No significant differences were observed at follow-up for the primary outcomes. The experimental group reported significantly lower Crohn's disease Symptom severity at T2 than the control group. Post-hoc analyses designed to mitigate floor effects revealed substantial treatment effects for the experimental group regarding anxiety symptoms. No significant differences were observed in clinical biomarkers from T0 to T3. Conclusion: The LIFEwithIBD intervention shows promising, although preliminary, benefits for managing disease activity and reducing anxiety symptoms in IBD patients with high severity of psychological distress. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory disease that most frequently affects part of the distal ileum, but it may affect any part of the gastrointestinal tract. CD may also be related to systemic inflammation and extraintestinal manifestations. Alzheimer's disease (AD) is the most common neurodegenerative disease, gradually worsening behavioral and cognitive functions. Despite the meaningful progress, both diseases are still incurable and have a not fully explained, heterogeneous pathomechanism that includes immunological, microbiological, genetic, and environmental factors. Recently, emerging evidence indicates that chronic inflammatory condition corresponds to an increased risk of neurodegenerative diseases, and intestinal inflammation, including CD, increases the risk of AD. Even though it is now known that CD increases the risk of AD, the exact pathways connecting these two seemingly unrelated diseases remain still unclear. One of the key postulates is the gut-brain axis. There is increasing evidence that the gut microbiota with its proteins, DNA, and metabolites influence several processes related to the etiology of AD, including b-amyloid abnormality, Tau phosphorylation, and neuroinflammation. Considering the role of microbiota in both CD and AD pathology, in this review, we want to shed light on bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation and provide an overview of the current literature on amyloids as a potential linker between AD and CD. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches. Methods: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis. Results: In the UC cohort, we reported the increase of Streptococcus, B ifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5- hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3- methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions. Conclusion: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a multi-organ chronic autoimmune disease. Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract. Previous studies have shown that SLE and IBD share common pathogenic pathways and genetic susceptibility, but the specific pathogenic mechanisms remain unclear. Methods: The datasets of SLE and IBD were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the Limma package. Weighted gene coexpression network analysis (WGCNA) was used to determine co-expression modules related to SLE and IBD. Pathway enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for co-driver genes. Using the Least AbsoluteShrinkage and Selection Operator (Lasso) regressionand Support Vector Machine-Recursive Feature Elimination (SVM-RFE), common diagnostic markers for both diseases were further evaluated. Then, we utilizedthe CIBERSORT method to assess the abundance of immune cell infiltration. Finally,we used the single-cell analysis to obtain the location of common diagnostic markers. Results: 71 common driver genes were identified in the SLE and IBD cohorts based on the DEGs and module genes. KEGG and GO enrichment results showed that these genes were closely associated with positive regulation of programmed cell death and inflammatory responses. By using LASSO regression and SVM, five hub genes (KLRF1, GZMK, KLRB1, CD40LG, and IL-7R) were ultimately determined as common diagnostic markers for SLE and IBD. ROC curve analysis also showed good diagnostic performance. The outcomes of immune cell infiltration demonstrated that SLE and IBD shared almost identical immune infiltration patterns. Furthermore, the majority of the hub genes were commonly expressed in NK cells by single-cell analysis. Conclusion: This study demonstrates that SLE and IBD share common diagnostic markers and pathogenic pathways. In addition, SLE and IBD show similar immune cellinfiltration microenvironments which provides newperspectives for future treatment. [ABSTRACT FROM AUTHOR]