Food-Grade Kappa-Carrageenan Induces Liver Injury through the FXR/FGF15 Pathway in Mice

Abstract Food-grade carrageenan (CGN) is widely used as a food additive, but its potential health risks remain controversial. This study investigated the effects of dietary food-grade kappa-CGN (κ-CGN) on liver health in mice. Our findings demonstrated that dietary κ-CGN induced liver inflammation, oxidative stress, and fibrosis. Metabolomic analyses identified elevated circulatory bile acids as a potential contributor to κ-CGN-induced liver injury. 16S rRNA sequencing revealed gut microbiota dysbiosis accompanied by increased proinflammatory cytokine production and altered fecal bile acid profiles. These disruptions dysregulated bile acid metabolism via the intestinal FXR/FGF15 signaling pathway, potentially resulting in the liver injury. Altered short-chain fatty acid profiles were also observed, representing an additional metabolic consequence of dysbiosis induced by κ-CGN. These results highlight the intricate interplay between gut microbiota, bile acid metabolism, and liver health, offering new insights into the metabolic risks associated with dietary exposure of food-grade κ-CGN.