Intestinal luminal anion transporters and their interplay with gut microbiome and inflammation

The intestine, as a critical interface between the external environment and the internal body, plays a central role in nutrient absorption, immune regulation, and maintaining homeostasis. The intestinal epithelium, composed of specialized epithelial cells, harbors apical anion transporters that primarily mediate the transport of chloride and bicarbonate ions, essential for maintaining electrolyte balance, pH homeostasis, and fluid absorption/secretion. In addition, the intestine hosts a diverse population of gut microbiota that plays a pivotal role in various physiological processes including nutrient metabolism, immune regulation, and maintenance of intestinal barrier integrity, all of which are critical for host gut homeostasis and health. The anion transporters and gut microbiome are intricately interconnected, where alterations in one can trigger changes in the other, leading to compromised barrier integrity and increasing susceptibility to pathophysiological states including gut inflammation. This review focuses on the interplay of key apical anion transporters including Down-Regulated in Adenoma (DRA, SLC26A3), Putative Anion Transporter-1 (PAT1, SLC26A6), and Cystic Fibrosis Transmembrane Conductance Regulator [CFTR, ATP-binding cassette subfamily C member 7 (ABCC7)] with the gut microbiome, barrier integrity, and their relationship to gut inflammation.