Oral iron exacerbates colitis and influences the intestinal microbiome

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS

The fungal microbiota of de-novo paediatric inflammatory bowel disease

Date of Acceptance:01/12/2014 Acknowledgements We are grateful for the expertise of our sequencing provider NewGene. We appreciate the generosity of the families who freely gave their time and samples to make this study possible and the theatre staff of all centres who allowed time for sample collection during busy endoscopy lists. This work was funded by a Clinical Academic Training Fellowship from the Chief Scientist Office in Scotland (CAF/08/01) which also funded the salary of RH, the Broad Medical Research programme and a project grant from NHS Grampian Endowments. The Yorkhill IBD team is generously supported by the Catherine McEwan Foundation and the Yorkhill IBD fund. RKR is supported by an NHS research Scotland fellowship. RKR has received support from a Medical Research Council (MRC) patient research cohorts initiative grant (G0800675) for PICTS.Peer reviewedPublisher PD

Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence

This work was supported in part by Department of Veterans Affairs Merit Review award BX000727 (to G.A.J.). The authors also acknowledge National Institutes of Health National Center for Research Resources Shared Instrumentation Grant S10 RR029446 (to H. E. Witkowska) for acquisition of the Synapt G2 high definition mass spectrometer, which is located at the University of California, San Francisco Sandler-Moore Mass Spectrometry Core Facility and supported by the Sandler Family Foundation, the Gordon and Betty Moore Foundation, National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA082103, and the Canary Foundation. G.A.J. is a recipient of the Senior Research Career Scientist award from the Department of Veterans Affairs. R.H. is funded by a Career Researcher Fellowship from NHS Research Scotland. The BISCUIT study was funded by a Clinical Academic Training Fellowship from the Chief Scientist Office (CAF/08/01). This is paper number 116 from the Center for Immunochemistry. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. K.B. acknowledges funding from the Child Health Research Charitable Incorporated Organisation and the Bogue Fellowship for travel. The authors declare that they have no conflicts of interest with the contents of this article.Peer reviewe

Comprehensive study of antiretroviral drug permeability at the cervicovaginal mucosa via an in vitro model

Funding: This work was supported by the European Union’s Seventh Programme for research, technological development and demonstration under grant agreement No 305316 as part of the MOTIF (Microbicides Formulation Through Innovative Formulation for Vaginal and Rectal Delivery) project. Acknowledgments: We thank all members of the MOTIF consortium for helpful discussions and exchange of ideas during the course of this study.Peer reviewedPublisher PD

Enterohepatic Helicobacter in ulcerative colitis:Potential pathogenic entities?

Background: Changes in bacterial populations termed "dysbiosis" are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC.Methodology/Principal Findings: A dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p&lt;0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR.Conclusions/Significance: Helicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.</p

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

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

The impact of different DNA extraction kits and laboratories upon the assessment of human gut microbiota composition by 16S rRNA gene sequencing

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The inflammatory microenvironment in colorectal neoplasia

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