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Eubacterium rectale detoxification mechanism increases resilience of the gut environment

Richie, T. G.; Wiechman, H.; Ingold, C.; Heeren, L.; Kamke, A.; Pogranichniy, S.; Monk, K.; Summers, T.; Ran, Q.; Sarkar, S.; Plattner, B. L.; Sidebottom, A. M.; Chang, E.; Lee, S. T. M.

2024-05-09 microbiology
10.1101/2024.05.09.593360 bioRxiv
Show abstract

Lachnospiraceae members were highly detected in dysbiotic IL-10 KO mice that displayed similar physiological outcomes as control mice. Lachnospiraceae is a highly diverse family of microbes that have been shown to display both commensal and pathogenic characteristics in the colon environment. We investigated the impact of genetic variation in five Lachnospiraceae strains on lowering cellular inflammation and ROS levels. Cell free spent media (CFSM) from Eubacterium rectale resulted in lowered ROS, and nitric oxide levels in stressed colon cells. We demonstrated through an array of multi omics and molecular techniques that glutathione (GSH) biosynthesized by E. rectale was able to alleviate host ROS damage. We further showed downregulation of cell stress and immune response genes by host RNA sequencing, which is evidence that E. rectale microbial products promote recovery and alleviate ROS stress. HighlightsO_LILachnospiraceae detection correlated with lower host inflammation in vertically transmitted dysbiotic mice C_LIO_LICell free spent media from E. rectale lowered ROS and nitric oxide levels when introduced to stressed Caco-2 cells more effectively than 4 other strains of Lachnospiraceae C_LIO_LIEubacterium rectale spent media products include high levels of glutathione (GSH), carbohydrates, and amino acids C_LIO_LIEubacterium rectale potential gene function for glutathione biosynthesis and metabolism found in the genome C_LIO_LILower expression of repair and stress genes of intestinal cells treated with hydrogen peroxide was observed with E. rectale CFSM as well as treatment with 15 mM GSH C_LI

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