Gene

Biology

Klebsiella oxytoca

Inflammatory bowel disease

Citrobacter

Morganella morganii

Immunology

Genetics

Microbiome

Bioinformatics

Klebsiella pneumoniae

Microbiology

Enterobacteriaceae

Escherichia coli

Internal medicine

Citrobacter freundii

Gut flora

Medicine

Proteus mirabilis

Disease

Metagenomics

Klebsiella

Frontiers in Cellular and Infection Microbiology

Objectives 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. Methods 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. Results Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli , Klebsiella variicola , Klebsiella quasipneumoniae , Klebsiella pneumoniae , Proteus mirabilis , Citrobacter freundii , and Citrobacter youngae , while Klebsiella oxytoca , Morganella morganii , and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis , Citrobacter pasteurii , Citrobacter werkmanii , and Proteus hauseri . Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains. Conclusions 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 E. coli and Klebsiella species.

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