Abstract
Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract that is often characterized by abdominal pain, rectal bleeding, inflammation, and weight loss. Many studies have posited that the gut microbiome may play an integral role in the onset and exacerbation of IBD. Here, we present a novel computational analysis of a previously published IBD dataset. This dataset consists of shotgun sequence data generated from fecal samples collected from individuals with IBD and an internal control group. Utilizing multiple external controls, together with appropriate techniques to handle the compositionality aspect of sequence data, our computational framework can identify and corroborate differences in the taxonomic profiles, bacterial association networks, and functional capacity within the IBD gut microbiome. Our analysis identified 42 bacterial species that are differentially abundant between IBD and every control group (one internal control and two external controls) with at least a twofold difference. Of the 42 species, 34 were significantly elevated in IBD, relative to every other control. These 34 species were still present in the control groups and appear to play important roles, according to network centrality and degree, in all bacterial association networks. Many of the species elevated in IBD have been implicated in modulating the immune response, mucin degradation, antibiotic resistance, and inflammation. We also identified elevated relative abundances of protein families related to signal transduction, sporulation and germination, and polysaccharide degradation as well as decreased relative abundance of protein families related to menaquinone and ubiquinone biosynthesis. Finally, we identified differences in functional capacities between IBD and healthy controls, and subsequently linked the changes in the functional capacity to previously published clinical research and to symptoms that commonly occur in IBD.
Highlights
Inflammatory bowel disease (IBD) is a heterogeneous disorder characterized by chronic inflammation of the gastrointestinal tract
For the Random Forest Classifier (RFC) analysis, the Healthy-1 and Healthy-2 cohorts were grouped under one label (Healthy) to create a single healthy control group to compare to the IBD and non-IBD sample groups allowing us to identify important features that distinguish between diagnosis groups rather than cohort in a more robust manner (Pasolli et al, 2016; Thomas et al, 2019)
This study identified numerous differences in taxonomic profiles, bacterial association networks, and genomic functional capacity between the IBD gut microbiome and the control gut microbiomes
Summary
Inflammatory bowel disease (IBD) is a heterogeneous disorder characterized by chronic inflammation of the gastrointestinal tract. While the etiology of IBD is not well understood, it is believed that the disorder arises due to environmental and host-related factors causing an aberrant immune response in genetically predisposed individuals (Kish et al, 2013; Chiara et al, 2020). One such factor is believed to be the microbiome, the gut microbiome (Duranti et al, 2016)
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