Sodium-Coupled Monocarboxylate Absorption in the Airway Epithelium Is Facilitated by the SLC5A8 Co-Transporter

Aim: Amino acids, sugars, short-chain fatty acids (SCFA), vitamins, and other small molecules compose the extracellular metabolome on the airway lumen surface, but how the airway epithelium deals with these molecules has not been deeply studied. Due to the broad spectrum of metabolites transported by SLC5A8 and SLC5A12, we aim to determine if they are functionally expressed and participate in the absorption of Na+, short-chain fatty acids, and monocarboxylates in mouse and human airway epithelium. Methods: Tracheas isolated from male or female mice and human bronchial epithelial cells (HBECs) were used for electrophysiological studies in the Ussing chamber and to detect members of the SLC16 family by RT-PCR and bulk RNAseq. Additionally, cell lines expressing the human and murine SLC5A8 transporter were employed for uptake studies using a fluorescent lactate probe. Results: We showed for the first time that human and murine airway epithelium express a functional SLC5A8 transporter, facilitating the absorption of glucose metabolites and SCFAs. The Na+-coupled monocarboxylate transport was not additive with ENaC-mediated Na+ absorption in mouse trachea. We observed that valproate acts as an inhibitor of the murine but not of the human SLC5A8 transporter. Conclusions: Our results demonstrate that several metabolites derived from bacterial and cellular metabolism can be transported from the airway lumen into the epithelial cells, participating in a homeostatic relation of the tissue with its environment.