The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls.

Comparative genomics and phenotypic studies to determine site-specificity of in the lower gastrointestinal tract of humans.

() is an important commensal in the human gut; however, it is unknown whether strains show site-specificity in the lower gut. To investigate this, we assessed genotypic and phenotypic differences in 37 clone pairs (two strains with very similar multiple locus variable-number-tandem-repeat analysis [MLVA] profiles) of isolated from mucosal biopsies of two different gut locations (terminal ileum and rectum). The clone pairs varied at the genomic level; single nucleotide polymorphisms (SNPs) were common, multiple nucleotide polymorphisms (MNPs) were observed but less common, and few indels (insertions and deletions) were detected.

Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study.

Introduction: Crohn's disease and ulcerative colitis are common chronic idiopathic inflammatory bowel diseases (IBD), which cause considerable morbidity. Although the precise mechanisms of disease remain unclear, evidence implicates a strong multidirectional interplay between diet, environmental factors, genetic determinants/immune perturbations and the gut microbiota. IBD can be brought into remission using a number of medications, which act by suppressing the immune response.

Psychological distress is highly prevalent in inflammatory bowel disease: A survey of psychological needs and attitudes.

Background And Aim: Data on patient needs and access to psychological services in inflammatory bowel disease (IBD) are scarce. This study aimed to describe the levels of distress and the needs, attitudes, and access to psychological services for people within Australia against established Australian IBD Standards.

Methods: An online cross-sectional survey was conducted with Australians ≥16 years old recruited via Crohn's & Colitis Australia membership, public and private clinics, and the Royal Flying Doctor Service.

Vedolizumab in combined immune checkpoint therapy-induced infliximab-refractory colitis in a patient with metastatic melanoma: A case report.

Background: Dual checkpoint inhibition improves response rates in treatment naïve patients with metastatic melanoma compared to monotherapy. However, it confers a higher rate of toxicity, including immune-related colitis. Steroids may not resolve symptoms in all cases.

Quality of care in inflammatory bowel disease: actual health service experiences fall short of the standards.

Background: Quality of care in inflammatory bowel disease (IBD) has received much attention internationally; however, the available surveys focus on health professionals rather than patients.

Aims: To assess the experiences of healthcare for people living with IBD against established Australian IBD Standards.

Methods: An online cross-sectional survey was conducted with Australians ≥16 years old recruited via Crohn's & Colitis Australia membership, public and private clinics and the Royal Flying Doctor Service.

Crohn's & Colitis Australia inflammatory bowel disease audit: measuring the quality of care in Australia.

Background: Australia has among the highest prevalence of Crohn disease and ulcerative colitis in the world. Management of the chronic gastrointestinal disorders results in significant societal costs and the standard of care is inconsistent across Australia.

Aim: To audit the quality of care received by patients admitted for inflammatory bowel disease (IBD) across Australia against national IBD standards.

The microbiome of Crohn's disease aphthous ulcers.

Background: Reduced intestinal microbial diversity and bacterial imbalance (dysbiosis) are seen in studies of Crohn's disease. As it is difficult to obtain biopsy samples before disease presentation, the earliest mucosal lesions in Crohn's disease, aphthous ulcers, present the best chance at assessing microbial communities at the onset of disease or a new flare. The aim of our study was to compare the microbial communities of aphthous ulcers and adjacent normal mucosa from patients with Crohn's disease with normal mucosa from controls.

Prevalence of Species in the Ileum of Crohn's Disease Patients and Controls.

are common contaminants of food products, but their prevalence in the human gut is poorly documented. have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gene of and the gene of .

The microbiome of translocated bacterial populations in patients with and without inflammatory bowel disease.

Background: Using culture-based methods, bacterial translocation from the gut to draining mesenteric lymph nodes is seen in 5% of normal controls and up to 33% of patients with inflammatory bowel diseases (IBD). Many bacteria cannot be cultured, so these methods are unable to capture the full spectrum of bacteria present.

Aims: To detect viable bacteria in lymph nodes of patients with IBD and non-IBD controls using bacterial RNA as a surrogate for viability and to compare them with the same patient's gut microbiome.

Inflammatory bowel disease-related fatigue is correlated with depression and gender.

Objectives: Fatigue is a common and disabling problem in inflammatory bowel disease. We sought to explore the possible determinants of inflammatory bowel disease-associated fatigue including demographic, psychological and disease variables.

Methods: Surveys were distributed to 100 patients undergoing infliximab infusion for inflammatory bowel disease in an infusion lounge, assessing attachment style (Experiences in Close Relationships Revised scale), fatigue (Functional Assessment of Chronic Illness Therapy Fatigue - Fatigue Subscore), and depression and anxiety (Hospital Anxiety and Depression Scale).

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease.

Background: Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia.

The role of inflammation in temporal shifts in the inflammatory bowel disease mucosal microbiome.

Studies of the human intestinal microbiome in patients with inflammatory bowel disease (IBD) consistently show that there are differences (an abnormal or unbalanced microbiome, "dysbiosis") when compared to healthy subjects. We sought to describe changes in the microbiome in individual patients over time, and determine the clinical factors that are associated with significant alteration. Forty-two mucosal biopsies were collected from 20 patients that were spaced an average of 2.

Within-host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract.

When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E.

Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in inflammatory bowel disease patients.

Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform-like reactions are among the most common adverse reactions. We retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia.

Genital Granulomatosis in Male and Female Patients With Crohn's Disease: Clinical Presentation and Treatment Outcomes.

Background: Genital granulomatosis [GG] is a metastatic form of Crohn's disease [CD], characterised by granulomatous inflammation of the genital skin without contact with the gastrointestinal tract. Little is known about GG, as most publications are case reports or small series, and only sporadic in male cases.

Methods And Aims: Cases of GG were retrospectively collected through the Collaborative Network For Exceptionally Rare case reports project of the European Crohn's and Colitis Organisation.

Fine-Scale Structure Analysis Shows Epidemic Patterns of Clonal Complex 95, a Cosmopolitan Lineage Responsible for Extraintestinal Infection.

The lineage known as clonal complex 95 (CC95) is a cosmopolitan human-associated lineage responsible for a significant fraction of extraintestinal infections of humans. Whole-genome sequence data of 200 CC95 strains from various origins enabled determination of the CC95 pangenome. The pangenome analysis revealed that strains of the complex could be assigned to one of five subgroups that vary in their serotype, extraintestinal virulence, virulence gene content, and antibiotic resistance gene profile.

Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.

The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria.

Comparative genomics of Crohn's disease-associated adherent-invasive .

Objective: Adherent-invasive (AIEC) are a leading candidate bacterial trigger for Crohn's disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification.

Gut feelings 1. Mind, mood and gut in irritable bowel syndrome: approaches to psychiatric care.

Objective: Psychiatrists are likely to encounter patients with irritable bowel syndrome (IBS). We aim to provide a clinically-focused summary of psychiatric comorbidities and management.

Conclusions: IBS affects up to 15% of the population.

Gut feelings 2. Mind, mood and gut in inflammatory bowel disease: approaches to psychiatric care.

Objectives: The authors aim to provide a clinically-focused summary of psychiatric complications of inflammatory bowel disease (IBD), and give treatment recommendations.A narrative review of literature drawn from PubMed and Medline.

Conclusions: IBD is a chronic, debilitating and potentially body integrity altering condition with significant morbidity and a slight increase in mortality.

Escherichia coli diversity in the lower intestinal tract of humans.

Previous studies examining the clonal diversity of Escherichia coli populations within humans have been based on faecal isolates. In this study E. coli were isolated from biopsies taken from the terminal ileum, ascending, transverse and descending colon, and rectum of 69 individuals.

Detection of bacterial DNA in lymph nodes of Crohn's disease patients using high throughput sequencing.

Objective: Our aim was to determine whether or not specific microorganisms were transported selectively to lymph nodes in Crohn's disease (CD) by comparing node and mucosal microbial communities in patients and controls. We also sought evidence of dysbiosis and bacterial translocation.

Design: Lymph nodes, and involved and uninvolved mucosal samples were obtained from resections of 58 patients (29 CD, eight 'other inflammatory bowel disease' (IBD) and 21 non-IBD).

Impact of colonoscopy bowel preparation on intestinal microbiota.

The gut microbiota is important in maintaining human health, but numerous factors have the potential to alter its composition. Our aim was to examine the impact of a standard bowel preparation on the intestinal microbiota using two different techniques. Fifteen subjects undergoing colonoscopy consumed a bowel preparation comprised of 10 mg bisacodyl and 2 L polyethylene glycol.