Effect of Filamin A editing on the gut microbiome

Regulated host-microbiome crosstalk is vital to maintain intestinal homeostasis. The actin crosslinker Filamin A (FLNA), impacts cellular responses by interacting with a range of cytosolic proteins. It exists in two forms which only differ in one single amino acid, genome encoded FLNAQ and FLNAR, generated via post-transcriptional RNA editing. As FLNA editing is exceptionally high in the distal colon, we hypothesized that FLNA editing may impact ulcerative colitis (UC) susceptibility. Here, wee compared the susceptibility of mice which exclusively express unedited FLNAQ or edited FLNAR to DSS-induced colitis and dissected how the FLNA editing status affects transcriptional profile of key intestinal cell populations by single cell sequencing. Microbiomes of FLNA mutant mice were analyzed by 16S RNA sequencing followed by antibiotic depletion and cohousing approaches. Sequencing was performed at the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna under the project IDs JMF-2005-3 and JMF-2109-12.