Abstract

BackgroundInflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota. Herein we performed the multiomics analysis by combining the large scale surveys of gut bacterial community, stool microRNA (miRNA) and short chain fatty acid (SCFA) signatures to correlate their association with the activity of Crohn’s disease (CD).MethodsDNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16S rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively.ResultsPairwise comparisons showed that 9 and 23 taxa differed between controls and CD patients with active and inactive disease, respectively. Six taxa were common to both comparisons, whereas four taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value < 0.05; FC > 1.5) in CD patients and controls before FDR correction and 4 after. Of six SCFAs, the levels of two differed significantly (p-value < 0.05, FC > 1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with smallest error rate for controls in bacterial component and inactive disease in metabolites.ConclusionA complex interrelationship may exist between gut dysbiosis, miRNA profiling and SCFA level in response to intestinal inflammation.

Highlights

  • Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota

  • Infection of the alimentary tract with opportunistic pathogens usually leads to acute gastroenteritis, and disruption of the ecological organization of normal gut Ambrozkiewicz et al BMC Gastroenterology (2020) 20:307 microbiota, called dysbiosis, may lead to immune system defects associated with various chronic human disorders, including the inflammatory bowel diseases (IBDs) Crohn’s disease (CD) and ulcerative colitis (UC) [8, 9]

  • Microbial dysbiosis in IBD is associated with a reduction in bacterial diversity, with colonization by pathogenic bacteria deranging the stability of the entire bacterial community [14]

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Summary

Introduction

Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota. Microbial communities of the gastro-intestinal tract consist of at least 100 trillion microorganisms [1, 2] This complex ecosystem trains the immune system, protects against opportunistic pathogens, harvests nutrients and Infection of the alimentary tract with opportunistic pathogens usually leads to acute gastroenteritis, and disruption of the ecological organization of normal gut Ambrozkiewicz et al BMC Gastroenterology (2020) 20:307 microbiota, called dysbiosis, may lead to immune system defects associated with various chronic human disorders, including the inflammatory bowel diseases (IBDs) Crohn’s disease (CD) and ulcerative colitis (UC) [8, 9]. CD dysbiosis is associated with reductions in Bacteroidetes and Firmicutes, increases in Gammaproteobacteria and Enterobacteriaceae, increases in the isolation of adherent-invasive Escherichia coli from ileal CD biopsies, and reductions in Faecalibacterium prausnitzi commensal, strains of protective bacteria with antiinflammatory properties [15,16,17,18,19,20]

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