Slc9a1 plays a vital role in chitosan oligosaccharide transport across the intestinal mucosa of mice.

The mechanism underlying the intestinal transport of COS is not well understood. Here, transcriptome and proteome analyses were performed to identify potential critical molecules involved in COS transport. Enrichment analyses revealed that the differentially expressed genes in the duodenum of the COS-treated mice were mainly enriched in transmembrane and immune function. In particular, B2 m, Itgb2, and Slc9a1 were upregulated. The Slc9a1 inhibitor decreased the transport efficiency of COS both in MODE-K cells (in vitro) and in mice (in vivo). The transport of FITC-COS in Slc9a1-overexpressing MODE-K cells was significantly higher than that in empty vector-transfected cells (P < 0.01). Molecular docking analysis revealed the possibility of stable binding between COS and Slc9a1 through hydrogen bonding. This finding indicates that Slc9a1 plays a crucial role in COS transport in mice. This provides valuable insights for improving the absorption efficiency of COS as a drug adjuvant.