Breaching the intestinal barrier during cirrhosis: a cell-by-cell analysis of how diseased macrophages fail to prevent pathological bacterial translocation to the liver

In this project we will address the key clinical question of why the intestinal barrier becomes compromised in cirrhosis, by specifically focusing on the role of intestinal macrophages during barrier breakdown. We aim to map the transcriptome signatures of the functionally distinct niche-specific macrophages at a single cell level in the intestine using unique mouse models and clinically relevant patient samples. We further aim to establish a causal link between the breach in barrier integrity and intestinal macrophage absence or dysfunction. Defining these pathological macrophage subsets or dysfunctional programs may represent a major breakthrough in the cirrhosis research field.