INFLUENCE OF GUT MICROBIOTA COMPOSITION ON THE SEVERITY AND RECURRENCE OF INFLAMMATORY BOWEL DISEASE

Abstract

Inflammatory Bowel Disease (IBD) or Crohn disease and ulcerative colitis is an inflammatory GI disease with long history of accumulating body of literature that has shown microbial dysbiosis of the gut to be a causal agent of the disease. Their quantitative interdependence between certain shifts in microbes, efficient metabolic impacts and clinical results, however, is not clearly defined. It was a multi-center prospective cohort study, that recruited 312 participants (98 active severe IBD, 114 remission IBD, 100 healthy controls). The microbial profiling was done by using 16S rRNA sequencing and metagenomic shotgun sequencing of the fecal and mucosal biopsy samples. Measures of alpha and beta diversity, differential abundance measures, reconstruction of functional pathways, and measures of short-chain fatty acids were added to clinical disease activity measures (Harvey-Bradshaw Index, Partial Mayo Score), inflammatory biomarkers (calprotectin, CRP) and postoperative recurrence measures. A combination of the logistic regression coefficient of the most significant discriminative taxa were used to derive a composite Microbial Dysbiosis Index (MDI).The extreme changes in the microbes with active treatment of the patients with severe IBD were compared to the healthy controls i.e. loss of Shannon diversity, loss of Firmicutes and gain of Proteobacteria. The depletion of faecalibacterium prausnitzii was 4.82 and Escherichia coli was enriched 5.67. The metagenomics analysis revealed that the way of butyrate synthesis (65.6%), and augmentation of LPS biosynthesis (250.8) were decreased and increased respectively. In active disease, the overall amount of SCFA was decreased 53.3 percent. The MDI was also found to possess a high degree of diagnostic accuracy and also had a good correlation with the disease activity. The patients who had Crohn disease after surgery had increased MDI which predicted increased risk of endoscopic recurrence by 4.23.The authors of this article, have given the following definition of microbial dysbiosis: ecological disruption which can be measured and which is immensely functional and clinical in the pathogenesis of IBD. The calculated Microbial Dysbiosis Index is a strong diagnostic and prognostic biomarker that can be used to justify the use of microbial profiling as a precision medicine intervention of IBD and/or to justify the use of microbial restoration as a rational intervention.