Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

BackgroundSequencing-based analysis has become a well-established approach to deciphering the composition of the gut microbiota. However, due to the complexity of accessing sufficient material from colonoscopic biopsy samples, most studies have focused on faecal microbiota analysis, even though it is recognised that differences exist between the microbial composition of colonic biopsies and faecal samples. We determined the suitability of colonic lavage samples to see if it had comparable microbial diversity composition to colonic biopsies as they are without the limitations associated with sample size. We collected paired colonic biopsies and lavage samples from subjects who were attending for colorectal cancer screening colonoscopy.ResultsNext-generation sequencing and qPCR validation were performed with multiple bioinformatics analyses to determine the composition and predict function of the microbiota. Colonic lavage samples contained significantly higher numbers of operational taxonomic units (OTUs) compared to corresponding biopsy samples, however, diversity and evenness between lavage and biopsy samples were similar. The differences seen were driven by the presence of 12 OTUs which were in higher relative abundance in biopsies and were either not present or in low relative abundance in lavage samples, whilst a further 3 OTUs were present in higher amounts in the lavage samples compared to biopsy samples. However, predicted functional community profiling based on 16S ribosomal ribonucleic acid (rRNA) data indicated minimal differences between sample types.ConclusionsWe propose that colonic lavage samples provide a relatively accurate representation of biopsy microbiota composition and should be considered where biopsy size is an issue.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0207-9) contains supplementary material, which is available to authorized users.

BSG abstracts Introduction The human intestinal tract is a complex microbial ecosystem unique to every individual and contributing sufficient metabolic equivalents to be considered an organ in its own right. Dysbiosis is thought to contribute to the chronic inflammation which is involved in colorectal cancer (CRC) development. We have shown that the premalignant adenoma stage of CRC is underpinned by chronic inflammation and hypothesise that the colonic microbiota is an important driver of neoplastic progression. The aim of the study was to compare bacterial diversity in adenomas and paired adjacent normal colonic tissue. Methods 72 patients undergoing colonoscopy as part of the national bowel cancer screening programme were recruited. All patients underwent polypectomy for large adenomas (> 1cm). Denaturing gradient gel electrophoresis (DGGE on all subjects) and pyrosequencing (18 subjects) were used to compare the bacterial diversity present between the adenoma and adjacent normal paired tissue samples. Results 46% of patients showed differences in microbial diversity by DGGE analysis between adenoma and adjacent normal tissue. 21% had only limited differences whilst 79% showed dramatically altered diversity profiles. Phylum-level comparisons across the study cohort, based on sequencing, revealed no statistically significant differences for the Bacteroidetes, Firmicutes and Proteobacteria phyla. When samples were split based on DGGE analysis (i.e. similar or different DGGE profiles between paired polyp and normal mucosa), eight of the possible 10 phyla showed statistically significant differences. Collectively samples with similar profiles between polyp and normal tissue (DGGE 'same' group) had higher levels of Bacteroidetes and lower numbers of Actinobacteria, Firmicutes and Proteobacteria than the DGGE 'different' group. However when genus-level comparisons were assessed the DGGE 'different' sample pairs demonstrated a much greater level of dysbiosis. The levels of normal commensal genera were reduced and there was evidence of large numbers of potentially pathogenic bacteria including Shigella, Enterobacter and Fusobacteria spp. Conclusion Differences in microbial diversity harboured by a significant number of polyps compared to their immediately adjacent normal mucosa point to an important role for these bacteria in CRC progression. We hypothesise that the disturbed microbial homeostasis in these polyps, in genetically predisposed individuals and taking into account multiple environmental factors, underpins the pathogenesis of colorectal neoplasia. The identification of a "harmful" pro-inflammatory microbiota that is associated with precancerous stages (i.e. adenomas) offers the potential for manipulations of this microbiota with probiotic, prebiotic and indeed antibiotic means. Disclosure of Interest None Declared.

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Background: The finding of a mucosal granuloma on histological analysis of endoscopically obtained biopsies in children with Crohn’s disease has been suggested to provide prognostic information. The aim of this study was to retrospectively assess the rate of granuloma detection and the impact of this upon specific disease characteristics and outcomes in children diagnosed with Crohn’s disease. After identification of a group of children previously diagnosed with Crohn’s disease, chart reviews were undertaken to characterise the children as granuloma positive or negative. Disease characteristics at diagnosis (such as disease location and nutritional status) and following diagnosis (such as requirement for immunosuppressive medications and surgical intervention) were noted for each patient. Results: Ninety-four children from two distinct geographical areas were identified. Forty-nine (52.1%) of the children had mucosal granulomata. Children with colonic disease were likely to have granulomata detected (RR = 3.04; p < 0.001). Granulomata were associated with lower weight z-scores at diagnosis (p < 0.05), but not other disease features (e.g., perianal disease or extra-intestinal manifestations). The presence of a granuloma at diagnosis was also associated with increased rates of the subsequent requirement for an immunosuppressive medication (RR = 1.26; p = 0.002). The presence of granulomata on histological assessment of mucosal biopsies at diagnosis of children with Crohn’s disease appears to be associated with specific disease features and outcomes. These findings should be clarified prospectively in a larger cohort of children with Crohn’s disease.