[Mechanism of Picrorhizae Rhizoma against functional constipation in mice: an exploration based on 16S rDNA and GC-MS].

The study was designed to determine the influences of Picrorhizae Rhizoma on gut microbiota and metabolites in mice with functional constipation(FC). ICR mice were divided into the blank control group, model group, and the low-, middle-, and high-dose Picrorhizae Rhizoma groups. Mice in the model and low-, middle-, and high-dose Picrorhizae Rhizoma groups were modeled with loperamide hydrochloride. After successful modeling, the ones in the low-, middle-, and high-dose Picrorhizae Rhizoma groups were gavaged with Picrorhizae Rhizoma at the corresponding doses for seven days. The first appearance time of tarry stool, the total fecal volume within 3 h, the fecal moisture content, and the intestinal transit rate were observed in each group. The pathological changes in intestinal mucosa were detected by HE staining. The flora dynamics in colon content were measured by 16 S rDNA sequencing, followed by the examination of fecal metabolomic profiles by gas chromatography-mass spectrometry(GC-MS). The results showed that the first appearance time of tarry stool in the model group was prolonged. The total fecal volume within 3 h, the fecal moisture content, and the intestinal transit rate were significantly reduced. The colon tissue showed inflammatory cell infiltration. Gut microflora and fecal metabolites changed dramatically. Picrorhizae Rhizoma alleviated the constipation symptoms, repaired intestinal mucosa, and partially restored the gut microbiota and metabolite compositions in mice with constipation. As demonstrated by intestinal microbiota sequencing, Picrorhizae Rhizoma remarkably reduced the Firmicutes/Bacteroidetes ratio and the relative abundance of Lactobacillus, but increased the relative abundance of Muribaculaceae, Enterorhabdus, and Eggerthellaceae. According to the linear discriminant analysis effect size(LefSe), the dominant bacterial species in the Picrorhizae Rhizoma groups were Muribaculaceae, Dubosiella, and Akkermansia. A total of 43 differential metabolites were detected in the feces of mice, involving the D-glutamine and D-glutamate metabolism, glutathione metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, purine metabolism, and pyrimidine metabolism. All these have demonstrated that Picrorhizae Rhizoma enhanced gastrointestinal motility, protectd gastrointestinal mucosa, and alleviated constipation symptoms possibly by regulating the intestinal microbial communities and metabolites and affecting the related metabolic pathways.