Exposure to Grilled Lamb-Borne Carbon Quantum Dots Induces Intrahepatic Cholestasis by Activating the Intestinal...

The by-products of thermally processed foods, carbon quantum dots (CQDs), pose unpredictable risks to human health due to their nanoscale size and abundant surface functional groups that can readily accumulate in organs. Herein, mice were oral-exposed to grilled lamb-derived CQDs (25 mg kg^-1) for 9 weeks. The results indicated that CQDs exposure resulted in liver and intestinal barrier injury, as well as an increase in intestinal microbiota-derived lipopolysaccharide (LPS). CQDs exposure directly and indirectly upregulated the expression of bile acid (BA) synthesis genes (Cyp7a1, Cyp8b1, and Cyp27a1) by activating MyD88 in the intestinal LPS-TLR4 pathway, as well as MyD88 and NFκB, downstream molecules of LPS-TLR4 pathway in the liver, leading to increased BA synthesis. Concurrently, the expression of BA excretion genes Bsep and Mrp2 was downregulated, contributing to cholestasis. With prolonged exposure, the levels of the farnesoid X receptor (FXR) inhibitor tauro-β-muricholic acid increased, while that of agonists chenodeoxycholic acid and taurochenodeoxycholic acid decreased, further exacerbating cholestasis. Supplementation with Lactiplantibacillus plantarum ATCC8014 mitigated cholestasis by reducing the relative abundance of g_Flexispira, increasing the relative abundance of g_Adlercreutzia, and remodeling the intestinal barrier. This study provides substantial evidence for the comprehensive assessment, control, and intervention regarding the hepatotoxicity of foodborne CQDs.