Anthocyanin-rich lingonberry extract improves intestinal homeostasis based on intestinal stem cells in high-fat-diet-fed mice via gut microbiota-mediated Wnt/PPAR signaling

Abstract

The Western diet impairs physiological health and leads to intestinal dysfunction. Lingonberries have the potential to ameliorate intestinal damage, although the underlying mechanisms are unclear. Here, the modulatory action of lingonberry anthocyanins on intestinal homeostasis in high-fat diet (HFD)-fed mice was investigated from the perspective of the intestinal flora-intestinal stem cells (ISCs) axis. The anthocyanin composition of lingonberry (Vaccinium vitis-idaea L.) extract was determined by high-performance liquid chromatography (HPLC). Anthocyanin-rich lingonberry extract (ARLE) was administered to HFD-fed mice for 9 weeks. Intestinal injury and ISCs fitness were analyzed by qPCR, immunofluorescence, and Western Blot. Moreover, the gut microbiota was analyzed by 16S rRNA sequencing and jejunum was used for RNA sequencing (RNA-Seq). The results showed that ARLE contained a total of 20 anthocyanins, which accounted for 36.0% of the extract. ARLE may balance intestinal homeostasis by enhancing the intestinal barrier and maintaining steady-state proliferation and differentiation of ISCs. RNA-seq revealed that ARLE supplementation improved the immune response and ISCs homeostasis by modulating Wnt/PPAR signaling, and this was potentially related to the gut microbiota. Our findings support that ARLE improved gut homeostasis and attenuated HFD-induced injury by regulating the gut microbiota-ISCs axis via Wnt/PPAR signaling.