Role of epithelial reactive oxygen production for interactions with the microbiome

Background and current state of research
Reactive oxygen species (ROS) serve as one line of defense against pathogenic infection due to their high antibacterial activity. However, chronic or overactivation of ROS production also leads to tissue and DNA damage and thereby to susceptibility for inflammation and cancer. In previous work we identified the microbiome as potent regulator of intestinal epithelial ROS responses (Sommer & Bäckhed 2015 Mucosal Immunology; Sommer et al. 2015 Genome Biology). This led us to hypothesize that intestinal ROS production critically determines host-microbiome interactions and thereby intestinal physiology.

Our goals
Our goal is to decipher the function of epithelial ROS production for the selection of the microbiome and how defects in this process may affect susceptibility to intestinal inflammation, cancer and metabolic disease.

How to get there
We will investigate the phenotype and disease susceptibility of mice lacking a key ROS producing enzyme in the intestinal epithelium. Additionally, we will screen for microbial factors regulating epithelial ROS production by using in vitro assays.

References
Sommer & Bäckhed „The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium” Mucosal Immunol. 2015 Mar;8(2):372-9. doi: 10.1038/mi.2014.74.
Sommer et al. „Site-specific Programming of the Host Epithelial Transcriptome by the Gut Microbiota”. Genome Biology. 2015 Mar 28;16:62. doi: 10.1186/s13059-015-0614-4.

Team
PhD student (tbd.)

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