Functional analysis of metalloenzymes from human gut microbiota and their role in ulcerative colitis.

AIM: Metalloenzymes produced by gut microbiota play an essential role in various physiological processes, and maintains homeostasis of gastrointestinal tract. Our study includes functional analysis of microbial metalloenzymes using metagenomics and metatranscriptomics data from Inflammatory Bowel Disease Multiomics Database. METHODS AND RESULTS: The distance matrix calculated by using metalloenzymes data produced significant results for bacterial taxonomy, with higher variance compared to HMP analysis in both Western and Indian population. Differential gene expression analysis revealed altered expression of ulcerative colitis (UC)-associated enzymes, increased folds changes in Prevotella and Megamonas transcripts; whereas, low transcripts of Alistipes genera. Further, docking and simulation studies performed on screened UC-associated enzymes revealed changes in catalytic efficiency and ligand interacting residues. CONCLUSION: The ß-diversity using microbes containing metalloenzymes suggests considering small group of specific genes or enzymes for understanding the diversity between UC and healthy individuals. The docking and differential gene expression analysis collectively indicate the probable role of metalloenzymes and few UC-associated enzymes in the severity of UC.

Gut colonization with antibiotic resistance Escherichia coli pathobionts leads to disease severity in ulcerative colitis.

AIM: Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored till date. METHODS: Human gut microbiota composition and meta-gut resistome was evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to get insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. RESULTS: In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy control (HC) [518]. Metagenome study revealed higher prevalence of AMR genes in rural population (378 in HC; 607 in UC) compared to urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and immuneproteins (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. CONCLUSIONS: In addition to the conventional culturomics method, multi-omics strategy provides deeper insights into the disease etiology, emergence of pathobionts, andits role in the disruption of the healthy gut environment in UC patients.

Draft genome sequence of Kluyvera ascorbata HAK22 isolated from human feces.

The whole genome sequence of rare human pathogen Kluyvera ascorbata strain HAK22 is reported. The K. ascorbata HAK22 was isolated from healthy human from Gurugram, Haryana, India. The draft genome has a length of 4.7 Mbp, with 54.36% GC content and 4,411 proteins, 4,470 genes, and 18 antimicrobial resistance genes.