SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs

Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression, but the absorption mechanism remains unknown. Here, we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs. SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs. Notably, we identified the stomach as the primary site for dietary microRNA absorption, which is dramatically attenuated in the stomachs of SIDT1-deficient mice. Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent. Furthermore, oral administration of plant-derived miR2911 retards liver fibrosis, and this protective effect was abolished in SIDT1-deficient mice. Our findings reveal a major mechanism underlying the absorption of dietary microRNAs, uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.

Automated summary

The study reveals that SIDT1 expressed on gastric pit cells is necessary for the absorption of dietary microRNAs, and deficiency in SIDT1 leads to reduced absorption. The stomach is identified as the primary site for dietary microRNA absorption, and the process relies on SIDT1 and low pH. Oral administration of plant-derived miR2911 can delay liver fibrosis, but this effect is nullified in SIDT1-deficient mice.