Innate Immune Sensors and Gastrointestinal Bacterial Infections

The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively (Helicobacter pylori infection, Salmonella infection, and inflammatory bowel disease). Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases

First-Pass Meconium Samples from Healthy Term Vaginally-Delivered Neonates : An Analysis of the Microbiota

Acknowledgments The authors would like to thank the parents who consented to provide samples with limited notice at an emotional and stressful time. This work was supported entirely from personal donations to the neonatal endowments fund at Aberdeen Maternity Hospital and we thank families for their continued generosity, year-on-year. The Rowett Institute of Nutrition and Health receives funding from the Scottish Government (SG-RESAS). Funding: This work was funded from NHS Grampian Neonatal Endowments. The Rowett Institute receives funding from the Rural and Environmental Science and Analytical Services programme of the Scottish Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The gut virome:the ‘missing link’ between gut bacteria and host immunity?

The human gut virome includes a diverse collection of viruses that infect our own cells as well as other commensal organisms, directly impacting on our well-being. Despite its predominance, the virome remains one of the least understood components of the gut microbiota, with appropriate analysis toolkits still in development. Based on its interconnectivity with all living cells, it is clear that the virome cannot be studied in isolation. Here we review the current understanding of the human gut virome, specifically in relation to other constituents of the microbiome, its evolution and life-long association with its host, and our current understanding in the context of inflammatory bowel disease and associated therapies. We propose that the gut virome and the gut bacterial microbiome share similar trajectories and interact in both health and disease and that future microbiota studies should in parallel characterize the gut virome to uncover its role in health and disease

Innate immune sensors and gastrointestinal bacterial infections.

The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively (Helicobacter pylori infection, Salmonella infection, and inflammatory bowel disease). Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases.Peer Reviewe

A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

New insights on the population genetic structure of the great scallop (Pecten maximus) in the English Channel coupling microsatellite data and demogenetic simulations.

International audienceThe great scallop (Pecten maximus) is a commercially important bivalve in Europe, particularly in the English Channel, where fisheries are managed at regional and local scales through the regulation of fishing effort. In the long term, knowledge about larval dispersal and gene flow between populations is essential to ensure proper stock management. Yet, previous population genetic studies have reported contradictory results. In this study, scallop samples collected across the main fishing grounds along the French and English coasts of the English Channel (20 samples with temporal replicates for three sites,n= 1059 individuals), and the population genetic structure was analysed using 13 microsatellite loci. Coupling empirical genetic data with demogenetic modelling based on a biophysical model simulating larval exchanges among scallop beds revealed a subtle genetic differentiation between south-west English populations and the rest of the English Channel, which was consistent with larval dispersal simulations. The present study provides a step forward in the understanding of great scallop population biology in the English Channel, underlining the fact that even in a context of potentially high gene flow and recent divergence times since the end of the last glacial maximum, weak but significant spatial genetic structure can be identified at a regional scale

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. However, none of the available medications address any of the underlying potential mechanisms. As we understand more about how the microbiota drives inflammation, much interest has focused on identifying microbial signals/triggers in the search for effective therapeutic targets. We describe the establishment of the Australian IBD Microbiota (AIM) Study, Australia's first longitudinal IBD bioresource, which will identify and correlate longitudinal microbial and metagenomics signals to disease activity as evaluated by validated clinical instruments, patient-reported surveys, as well as biomarkers. The AIM Study will also gather extensive demographic, clinical, lifestyle and dietary data known to influence microbial composition in order to generate a more complete understanding of the interplay between patients with IBD and their microbiota. METHODS: The AIM Study is an Australian multicentre longitudinal prospective cohort study, which will enrol 1000 participants; 500 patients with IBD and 500 healthy controls over a 5-year period. Assessment occurs at 3 monthly intervals over a 24-month period. At each assessment oral and faecal samples are self-collected along with patient-reported outcome measures, with clinical data also collected at baseline, 12 and 24 months. Intestinal tissue will be sampled whenever a colonoscopy is performed. Dietary intake, general health and psychological state will be assessed using validated self-report questionnaires. Samples will undergo metagenomic, transcriptomic, proteomic, metabolomic and culturomic analyses. Omics data will be integrated with clinical data to identify predictive biomarkers of response to therapy, disease behaviour and environmental factors in patients with IBD. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the South Eastern Sydney Local Health District Research Ethics Committee (HREC 2019/ETH11443). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619000911190