Multi-omics joint analysis: Arctii Fructus extract alleviates functional constipation by modulating microbiota-host co-metabolism and suppressing NLRP3 inflammasome activation.

Abstract

Functional constipation (FC) has become a prevalent gastrointestinal disorder worldwide. Arctii Fructus, a plant used for both food and medicine, contains oils, dietary fiber and arctiin as its core components, which have been demonstrated to alleviate constipation. However, its underlying mechanisms remain unclear. This study evaluated the interventive effects of the water extract of Arctii Fructus (WAF) in constipated mice induced by loperamide. Integrated metabolomics and 16S rDNA sequencing revealed that WAF significantly reshaped the gut microbiota structure, regulated the plasma metabolic profile, and inhibited the glycerophospholipid metabolism pathway in constipated mice. MetOrigin analysis further indicated that microbiota-host interactions play a critical role in WAF-mediated constipation relief. Serum pharmacochemical analysis identified five WAF-dependent active components that were absorbed into the bloodstream following microbial transformation. Based on network pharmacology predictions, we proposed that WAF alleviates constipation by suppressing the NLRP3 inflammasome pathway. This mechanism was subsequently validated through assessment of the spleen index, histopathological examination of intestinal tissues, and detection of key protein expression in the NLRP3 signaling pathway. In conclusion, this study systematically elucidates the multi-dimensional mechanisms by which WAF alleviates functional constipation through the gut microbiota-metabolism-inflammation axis. These findings provide a solid scientific foundation for its development as a functional food to improve intestinal health.