Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota
Cell Host Microbe. 2024 Feb 23:S1931-3128(24)00042-8. doi: 10.1016/j.chom.2024.02.003. Online ahead of print.ABSTRACTReversible genomic DNA inversions control the expression of numerous gut bacterial molecules, but how this impacts disease remains uncertain. By analyzing metagenomic samples from inflammatory bowel disease (IBD) cohorts, we identified multiple invertible regions where a particular orientation correlated with disease. These include the promoter of polysaccharide A (PSA) of Bacteroides fragilis, which induces regulatory T cells (Tregs) and ameliorates experimental colitis. The PSA promoter was mostly oriented "OFF" in IBD patients, which correlated with increased B. fragilis-associated bacteriophages. Similarly, in mice colonized with a healthy human microbiota and B. fragilis, induction of colitis caused a decline of PSA in the "ON" orientation that reversed as inflammation resolved. Monocolonization of mice with B. fragilis revealed that bacteriophage infection increased the frequency of PSA in the "OFF" orientation, causing reduced PSA expression and decreased Treg cells. Altogether, we reveal dynamic bacterial phase variations driven by bacteriophages and host inflammation, signifying bacterial functional plasticity during disease.PMID:38423015 | DOI:10.1016/j.chom.2024.02.003
Source: Cell Host and Microbe - Category: Microbiology Authors: Shaqed Carasso Rawan Zaatry Haitham Hajjo Dana Kadosh-Kariti Nadav Ben-Assa Rawi Naddaf Noa Mandelbaum Sigal Pressman Yehuda Chowers Tal Gefen Kate L Jeffrey Juan Jofre Michael J Coyne Laurie E Comstock Itai Sharon Naama Geva-Zatorsky Source Type: research