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Updated: Feb 26, 2026

Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease
Published on: February 9, 2016
VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against
Xin Yi1, Shiqing Zhang2,3, Xinpei Gu1
1Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
None:
Enterocytes mediate both nutrient absorption and antimicrobial peptide (AMP) secretion while constantly exposed to osmotic fluctuations. However, the role of volume-regulated anion channel (VRAC), a key osmo-sensitive ion channel, in enterocytes and inflammatory bowel disease (IBD) remains unclear. Here, we show that intestinal epithelial cell (IEC)-specific knockout of LRRC8A, the essential VRAC subunit, exacerbates colitis and inflammation-associated colorectal cancer. VRAC deficiency specifically disrupts enterocyte maturation and zonation, expanding AMP-producing enterocytes while reducing enterocytes responsible for nutrient absorption. Retinoic acid metabolism emerges as the most affected nutrient pathway in VRAC-deficient IECs, with reduced Adh1, Aldh1a2 expression and aldehyde dehydrogenase activity. Supplementation with retinoic acid reversed inflammation caused by VRAC deficiency. Conversely, VRAC deficiency induced gut microbiota dysbiosis, while administration of Lactobacillus species effectively restored microbial balance and alleviated inflammation. This study delineates the role of VRAC in balancing nutrient absorption and antimicrobial defense in enterocytes to safeguard gut homeostasis.
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