AUTHOR=Khorsand Babak , Asadzadeh Aghdaei Hamid , Nazemalhosseini-Mojarad Ehsan , Nadalian Bahareh , Nadalian Banafsheh , Houri Hamidreza 

TITLE=Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1015890

DOI=10.3389/fcimb.2022.1015890

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.</p></sec><sec><title>Methods</title><p>Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi’omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.</p></sec><sec><title>Results</title><p>Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including <italic>Escherichia coli</italic>, <italic>Klebsiella variicola</italic>, <italic>Klebsiella quasipneumoniae</italic>, <italic>Klebsiella pneumoniae</italic>, <italic>Proteus mirabilis</italic>, <italic>Citrobacter freundii</italic>, and <italic>Citrobacter youngae</italic>, while <italic>Klebsiella oxytoca</italic>, <italic>Morganella morganii</italic>, and <italic>Citrobacter amalonaticus</italic> were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including <italic>Citrobacter portucalensis</italic>, <italic>Citrobacter pasteurii</italic>, <italic>Citrobacter werkmanii</italic>, and <italic>Proteus hauseri</italic>. Our analysis also showed a dramatically increased abundance of <italic>E. coli</italic> in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by <italic>E. coli</italic> were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to <italic>K. pneumoniae</italic> strains.</p></sec><sec><title>Conclusions</title><p>In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly <italic>E. coli</italic> and <italic>Klebsiella</italic> species.</p></sec>