Quercetin Improves Postmenopausal Osteoporosis in Rats by Regulating the Intestinal Microbiota and Microbial Metabolism

Abstract

Background: Liuwei Dihuang pills contain quercetin, which has been found to alleviate postmenopausal osteoporosis (PMOP) progression. This study aimed to investigate the effects of quercetin on the intestinal microbiota and microbial metabolism in rats suffering from PMOP. Methods: The Sprague Dawley female rats were randomly divided into four groups (n = 5): sham, ovariectomized (OVX), quercetin-low dose (50 mg/kg/d), and quercetin-high dose (100 mg/kg/d). The optimal dose group (quercetin-high dose group) was used as the quercetin group for follow-up experiments. The histopathological changes in the tibia of rats were observed using hematoxylin-eosin (HE) and Masson staining. The composition and abundance of intestinal microbiota were determined using 16S rRNA sequencing, while metabolite levels were assessed using metabolomics. Pearsons correlation analysis was used to investigate the relationship between microbiota abundance and metabolite levels. Results: The administration of quercetin helped to prevent the degradation of the collagen fiber layer on the surface and the formation of fibrosis of femur tissue caused by OVX. Additionally, treatment with quercetin significantly increased species abundance and evenness in the OVX group. In contrast to the OVX group, quercetin treatment increased Muribaculaceae abundance and decreased the Clostridium sensu stricto 1 abundance. Major differential metabolites, such as pregnenolone, 3-aminobutyric acid, 2-aminoisobutyrate, N-methyl-L-alanine, and aminoisobutanoate, were found between the OVX and quercetin groups. Correlations between the abundance of Muribaculaceae and Clostridia UCG 014 and the major differential metabolites were found, respectively. Furthermore, the amino acid metabolic pathways were found to be the primary pathway for intestinal microbiota. Conclusions: The active ingredient quercetin regulates intestinal microbiota and microbial metabolism, helping to alleviate the symptoms of PMOP in rats.