The cellular states and fates of shed intestinal cells

The intestinal epithelium is replaced every few days¹. Enterocytes are shed into the gut lumen predominantly from the tips of villi^2,3 and have been believed to rapidly die upon their dissociation from the tissue^4,5. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.