AUTHOR=Roche-Lima Abiel , Carrasquillo-Carrión Kelvin , Gómez-Moreno Ramón , Cruz Juan M. , Velázquez-Morales Dayanara M. , Rogozin Igor B. , Baerga-Ortiz Abel 

TITLE=The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00116

DOI=10.3389/fgene.2018.00116

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects.</p><p><bold>Methods:</bold> The eight selected gene sequences were <italic>clbN, clbB, cif, cnf-1, usp, tcpC</italic> from <italic>Escherichia coli, gelE</italic> from <italic>Enterococcus faecalis</italic> and <italic>murB</italic> from <italic>Akkermansia muciniphila</italic>. We also included the sequences for the conserved <italic>murB</italic> genes from <italic>E. coli</italic> and <italic>E. faecalis</italic> as markers for the presence of <italic>Enterobacteriaceae</italic> or <italic>Enterococci</italic> in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (<italic>N</italic> = 251), a Crohn’s disease cohort (<italic>N</italic> = 60) and an ulcerative colitis cohort (<italic>N</italic> = 17).</p><p><bold>Results:</bold> Firstly, the sequences for the <italic>murB</italic> housekeeping genes from <italic>Enterobacteriaceae</italic> and <italic>Enterococci</italic> were more frequently found in the IBD cohorts (32% <italic>E. coli</italic> in IBD <italic>vs.</italic> 12% in healthy; 13% <italic>E. faecalis</italic> in IBD <italic>vs.</italic> 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially <italic>usp</italic> and <italic>gelE</italic>, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of <italic>E. coli</italic> or <italic>E. faecalis</italic> in those samples.</p><p><bold>Conclusion:</bold> Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.</p>