Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

Background: Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied.

Methods: All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included.

Discordant Effects of Janus Kinase Inhibition Ex Vivo on Inflammatory Responses in Colonic Compared to Ileal Mucosa.

Background And Aims: Janus kinase [JAK] inhibitors are used for treating inflammatory bowel diseases [IBD]. We aimed to identify the molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype.

Methods: Colonic and ileal explants from patients with ulcerative colitis [UC], Crohn's disease [CD], and non-IBD controls [NC] were assessed for levels of phosphorylated signal transducers and activators of transcription [p-STAT] and expression of inflammatory genes in response to an ex vivo JAK inhibitor [tofacitinib].

A Real-World Prospective Cohort Study of Patients With Newly Diagnosed Crohn's Disease Treated by a Multidisciplinary Team: 1-Year Outcomes.

Background: Real-world data on outcomes of patients with newly diagnosed Crohn's disease (ndCD) is limited. We aimed to assess the achievement of corticosteroid-free clinical remission (CS-free CR) and other therapeutic targets 1 year after diagnosis in a cohort of patients with ndCD treated by a multidisciplinary team (MDT).

Methods: A prospective observational cohort study was conducted on consecutive treatment-naïve adults with ndCD.

Human intestinal epithelial cells can internalize luminal fungi LC3-associated phagocytosis.

Background: Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the β-glucan receptor Dectin-1, and respond to commensal fungi and β-glucans. In phagocytes, Dectin-1 mediates LC3-associated phagocytosis (LAP) utilizing autophagy components to process extracellular cargo.

Newly Diagnosed Crohn's Disease Patients in India and Israel Display Distinct Presentations and Serological Markers: Insights from Prospective Cohorts.

Background: Crohn’s disease (CD) incidence is rising in India. However, features of newly diagnosed patients with CD in this population are largely unknown. The Indo-Israeli IBD GastroEnterology paRtnership (TiiiGER) aimed to investigate differences in presentation among patients with newly diagnosed CD in India and Israel, and to explore phenotype−serotype correlations.

SARS-CoV-2 IgG Antibody Levels in Women with IBD Vaccinated during Pregnancy.

Introduction: Regulatory agencies supported vaccination of pregnant women with SARS-CoV-2 mRNA vaccines, including patients with IBD. No data exist regarding these vaccines in IBD during pregnancy.

Aim: To assess the serologic response to two doses of the mRNA SARS-CoV-2 BNT162b2 vaccine in pregnant women with IBD vaccinated during pregnancy, compared to that of pregnant women without IBD, and non-pregnant women with IBD.

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses.

Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations.

Background And Aims: Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages.

Meta-Analysis of IBD Gut Samples Gene Expression Identifies Specific Markers of Ileal and Colonic Diseases.

Background: Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs).

Alteration in Urease-producing Bacteria in the Gut Microbiomes of Patients with Inflammatory Bowel Diseases.

Background And Aims: Bacterial urease is a major virulence factor of human pathogens, and murine models have shown that it can contribute to the pathogenesis of inflammatory bowel diseases [IBD].

Methods: The distribution of urease-producing bacteria in IBD was assessed using public faecal metagenomic data from various cohorts, including non-IBD controls [n = 55], patients with Crohn's disease [n = 291] or ulcerative colitis [n = 214], and patients with a pouch [n = 53]. The ureA gene and the taxonomic markers gyrA, rpoB, and recA were used to estimate the percentage of urease producers in each sample.

Dysbiosis in Metabolic Genes of the Gut Microbiomes of Patients with an Ileo-anal Pouch Resembles That Observed in Crohn's Disease.

Crohn's disease (CD), ulcerative colitis (UC), and pouchitis are multifactorial and chronic inflammatory bowel diseases (IBD). Pouchitis develops in former UC patients after proctocolectomy and ileal-pouch-anal anastomosis and is characterized by inflammation of the previously normal small intestine comprising the pouch. The extent to which microbial functional alteration (dysbiosis) in pouchitis resembles that of CD or UC has not been investigated, and the pathogenesis of pouchitis remains unknown.

Commensal fungi and their cell-wall β-glucans direct differential responses in human intestinal epithelial cells.

Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that β-glucans, major fungal cell-wall glycans, induced chemokine secretion by IEC lines in a Dectin-1- and Syk-dependent manner. Here, we show that in contrast to β-glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL-8, CCL2, CXCL1, and GM-CSF.

Early Indolent Course of Crohn's Disease in Newly Diagnosed Patients Is Not Rare and Possibly Predictable.

Background & Aims: The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis.

Methods: We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017.

Predominantly Antibiotic-resistant Intestinal Microbiome Persists in Patients With Pouchitis Who Respond to Antibiotic Therapy.

Background & Aims: Pouchitis that develops in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis is usually treated with antibiotics. Some patients have recurrence of flares, or become antibiotic-dependent, and require repeated courses or prolonged periods of antibiotic therapy. We investigated microbial factors associated with response to antibiotic treatment and development of antibiotic dependence in patients with pouchitis.

Gut microbiota density influences host physiology and is shaped by host and microbial factors.

Unlabelled: To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis.

Genotype-Serotype Interactions Shed Light on Genetic Components of Inflammatory Bowel Diseases.

Background: We evaluated the impact of variations in ATG16L1 and NOD2 and genes on serologic responses in patients with inflammatory bowel disease (IBD).

Methods: We recruited 308 IBD patients: 130 with Crohn's disease (CD), 67 with ulcerative colitis (UC), 111 with UC and an ileal pouch (UC-pouch), and 74 healthy controls. NOD2 variants (1007fs, G908R, R702W) and the ATG16L1 A300T variant were analyzed.

Increase in Processing Factors Is Involved in Skewed MicroRNA Expression in Patients with Ulcerative Colitis Who Develop Small Intestine Inflammation after Pouch Surgery.

Background: A large-scale increase in microRNA (miRNA) expression was observed in patients with ulcerative colitis who underwent pouch surgery and developed inflammation of the pouch (pouchitis). In this study, we assessed miRNA expression in these patients and investigated how regulation of its expression changes in the setting of pouchitis.

Methods: Autologous samples that included mucosal biopsies, peripheral blood cells, and plasma were collected from the patients.

Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD.

Objective: Although anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value.

Design: We analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition.

Transforming growth factor β signaling controls activities of human intestinal CD8(+)T suppressor cells.

Background & Aims: In healthy individuals, interactions between intestinal epithelial cells and lamina propria lymphocytes give rise to a population of CD8(+) T cells with suppressor functions (Ts cells). Disruption of Ts cell activities can lead to mucosal inflammation. We investigated what factors were required for expansion of the Ts cell population or loss of their activity in patients with Crohn's disease (CD).

Working out mechanisms of controlled/physiologic inflammation in the GI tract.

The mucosal immune system is distinct from its systemic counterpart by virtue of its enormous antigenic exposure (commensal flora, food antigen, pathogens). Despite this, the mucosal immune system maintains a response defined as controlled or physiologic inflammation. This is regulated by many different mechanisms, among which there are physical, cellular and soluble factors.

Notch-1 signaling regulates intestinal epithelial barrier function, through interaction with CD4+ T cells, in mice and humans.

Background & Aims: Interactions between lymphocytes and intestinal epithelial cells occur in the subepithelial space of the gastrointestinal tract. Normal human lamina propria lymphocytes (LPLs) induce differentiation of intestinal epithelial cells. The absence of LPLs in mice, such as in RAG1(-/-) mice, results in defects in epithelial cell differentiation.