The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn's disease-like ileitis.

Background And Aims: The renin-angiotensin system (RAS) is known to modulate fibrosis, which is a common complication of ileal Crohn's disease. We tested the efficacy of losartan, an angiotensin receptor blocker, to treat intestinal fibrosis in relevant preclinical models of Crohn's-like disease.

Methods: Effector molecules of the RAS were mined in a large publicly available RNA-Seq dataset of intestinal biopsies from Crohn's patients and healthy individuals, and the presence of associated proteins was confirmed by immunohistochemistry in full-thickness intestinal tissues.

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue.

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health.

A retrospective cohort study: pre-operative oral enteral nutritional optimisation for Crohn's disease in a UK tertiary IBD centre.

Background: Low-quality evidence suggests that pre-operative exclusive enteral nutrition (E/EN) can improve postoperative outcomes in patients with Crohn's disease (CD). It is not standard practice in most centres.

Aims: To test the hypothesis that pre-operative EN in patients undergoing ileal/ileocolonic surgery for CD is associated with improved postoperative outcome.

An observational study of switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with first or second switch.

Background: Biologics account for a significant cost in inflammatory bowel disease (IBD) management; however, switching from infliximab originator to its biosimilars has enabled cost saving without compromising disease control. The effects on IBD activity and infliximab trough levels of a second switch to another biosimilar are, however, uncertain.

Aims: To assess the effects on disease activity and infliximab trough levels associated with switching from infliximab biosimilar CT-P13 to another biosimilar SB2 and compare outcomes in those switching for the first and second time.

Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue.

Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom.

Background: Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP.

Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO-LEVEL study.

Background: Significant associations between serum golimumab concentrations and favourable outcomes have been observed during both induction and maintenance therapy in ulcerative colitis (UC). However, data regarding optimal therapeutic serum golimumab concentration thresholds are limited.

Aims: To identify optimal serum golimumab concentration thresholds during induction and maintenance treatment with golimumab.

Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease.

Background & Aims: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and biomarkers can calculate risk in asymptomatic first-degree relatives of patients with CD.

Methods: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom.

Reduced CD27IgD B Cells in Blood and Raised CD27IgD B Cells in Gut-Associated Lymphoid Tissue in Inflammatory Bowel Disease.

The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analyzed B cells in blood of patients with Crohn's disease (CD) and ulcerative colitis (UC) with a range of disease activities.

Streptococcus Salivarius: A Potential Salivary Biomarker for Orofacial Granulomatosis and Crohn's Disease?

Background: Orofacial granulomatosis (OFG) is a rare disease characterised by chronic, noncaseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohn's disease (CD), and a proportion of patients have both OFG and CD. The cause of OFG remains elusive, but it has been suggested that microbial interactions may be involved.

Promoter orientation of the immunomodulatory capsular polysaccharide A (PSA) is off in individuals with inflammatory bowel disease (IBD).

is a member of the normal microbiota of the lower gastrointestinal tract, but some strains produce the putative tumourigenic toxin (BFT). In addition, can produce multiple capsular polysaccharides that comprise a microcapsule layer, including an immunomodulatory, zwitterionic, polysaccharide A (PSA) capable of stimulating anti-inflammatory interleukin-10 (IL-10) production. It is known that the PSA promoter can undergo inversion, thereby regulating the expression of PSA.

Current Practices in Ileal Pouch Surveillance for Patients With Ulcerative Colitis: A Multinational, Retrospective Cohort Study.

Background And Aims: There are no universally accepted guidelines regarding surveillance of ulcerative colitis [UC] patients after restorative proctocolectomy and ileal pouch-anal anastomosis [IPAA]. There also exists a lack of validated quality assurance standards for performing pouchoscopy. To better understand IPAA surveillance practices in the face of this clinical equipoise, we carried out a retrospective cohort study at five inflammatory bowel disease [IBD] referral centres.

Validation and Investigation of the Operating Characteristics of the Ulcerative Colitis Endoscopic Index of Severity.

Background: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a novel instrument to evaluate endoscopic disease activity. It has been demonstrated to outperform the more widely used Mayo endoscopic score (MES) in predicting long-term prognosis, including the need for colectomy. Despite its potential benefits, many clinicians still prefer to use MES because its operating characteristics are better defined and its grades are more readily applicable to clinical decision-making.

Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue.

Human memory B cells and marginal zone (MZ) B cells share common features such as the expression of CD27 and somatic mutations in their IGHV and BCL6 genes, but the relationship between them is controversial. Here, we show phenotypic progression within lymphoid tissues as MZ B cells emerge from the mature naïve B cell pool via a precursor CD27CD45RB population distant from memory cells. By imaging mass cytometry, we find that MZ B cells and memory B cells occupy different microanatomical niches in organised gut lymphoid tissues.

Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer.

Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized.

Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota.

Background: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes.

Results: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO.

Thiopurines in Inflammatory Bowel Disease: New Findings and Perspectives.

Thiopurines, available as azathioprine, mercaptopurine, and thioguanine, are immunomodulating agents primarily used to maintain corticosteroid-free remission in patients with inflammatory bowel disease. To provide a state-of-the-art overview of thiopurine treatment in inflammatory bowel disease, this clinical review critically summarises the available literature, as assessed by several experts in the field of thiopurine treatment and research in inflammatory bowel disease.

Exome Sequencing and Genotyping Identify a Rare Variant in NLRP7 Gene Associated With Ulcerative Colitis.

Background And Aims: Although genome-wide association studies [GWAS] in inflammatory bowel disease [IBD] have identified a large number of common disease susceptibility alleles for both Crohn's disease [CD] and ulcerative colitis [UC], a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein-altering genetic variants are associated with susceptibility to IBD.

Methods: Whole-exome sequencing was carried out in 10 families in whom three or more individuals were affected with IBD.

Thiopurines Dosed to a Therapeutic 6-Thioguanine Level in Combination with Adalimumab Are More Effective Than Subtherapeutic Thiopurine-based Combination Therapy or Adalimumab Monotherapy During Induction and Maintenance in Patients with Long-standing Crohn's Disease.

Background: The benefit of concomitant immunomodulation with adalimumab (ADA) in Crohn's disease is poorly understood. We aimed to compare ADA monotherapy with combination therapy with thiopurines, stratified by thioguanine nucleotides (TGNs).

Methods: Retrospective observational study of ADA induction and maintenance.

Thioguanine in inflammatory bowel disease: Long-term efficacy and safety.

Background: Thioguanine (TG) is efficacious in inflammatory bowel disease (IBD), but its toxicity, particularly nodular regenerative hyperplasia (NRH) of the liver, has limited its use. We assessed the long-term clinical outcomes and safety of TG in patients whom were intolerant or refractory to conventional immunomodulators.

Methods: This is a retrospective, single-centre study of IBD patients treated with TG from 2001-2013.