Postmenopausal osteoporosis (PMO) is the most common primary osteoporosis. It is due to the decrease of bone strength and the increase of bone fragility caused by estrogen deficiency after menopause. Intestinal flora is closely related to bone metabolism, and bone mineral density of patients with excessive intestinal growth is significantly reduced. Neuropeptide Y (Neuropeptide Y, NPY) can directly play an antibacterial role on the intestinal tract through the Y1 receptor (Y1R). Can NPY play an anti osteoporosis role by regulating the intestinal flora in rats? How does intestinal microflora interact with bone metabolism?
In December 6, 2019, the Li Zhanchun research group and the Xiao Jie research group of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine used the OVX rat model and treated with Y1R antagonist. It was observed that the Y1R antagonist could play an anti osteoporosis role by regulating the intestinal flora. Strong ice technology provides support for 16S rRNA sequencing data analysis in this work. The research results are published in the magazine "Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy the".
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Effects of 1. Y1R antagonist on body weight and serum biochemical indices of OVX rats
Figure 1 showed that compared with group SHAM, the weight of rats in OVX group increased significantly, serum E2 concentration decreased significantly, and showed a lower Ca. 2+ Concentration and higher Pi concentration level. After treatment with Y1R antagonist, In group OVX+BIBO3304, the body weight of rats was significantly reduced, which was the same as that of group SHAM, and Ca 2+ And Pi levels were improved. 。
Fig. 1 Effect of Y1R antagonist on body weight and serum biochemical indices of OVX rats
Two Y1R antagonist improves bone mass and bone microstructure in OVX rats
Histological analysis of the right tibia microCT and HE staining showed that the cancellous bone in the OVX group became thinner and the regular mesh structure was lost. The parameters BMD and BV/Tv decreased significantly and SMI increased. and Group OVX+BIBO3304 rats Y1R After treatment with antagonist, the structure and indicators of cancellous bone were improved. 。
Fig. 2 Y1R antagonist improves bone mass and bone microstructure in OVX rats.
3. Y1R antagonist regulates microbial diversity in OVX rats
Chao1 and Shannon curves were used to analyze the diversity of intestinal flora (map 3a and b). There was no significant difference in microbial species richness (Chao1) and diversity (Shannon) between the three groups. The microbial community structure (beta diversity) was analyzed by PCoA analysis (map 3C, d). The structure of intestinal bacteria in the three groups was clearly separated. Ovarian resection and Y1R antagonist treatment are key factors in the microbial community structure. 。
Fig. 3 regulation of Y1R antagonist on microbial diversity in OVX rats
4. Y1R antagonist changes the composition of intestinal microbial community in OVX rats
Fig. 4a-c describes the microbial composition of three groups at the taxonomy of phylum, genus and genus. Firmicutes And Bacteroides ( Bacteroidetes ) The serum F/B ratio (4.05) in group OVX was significantly higher than that in group SHAM (2.18). After treatment with Y1R antagonist, the F/B ratio (2.61) was significantly improved, and the abundance of lactic acid bacteria also changed (SHAM: 4.4%, OVX: 2.4%, OVX+BIBO3304:3.6%).
Fig. 4 Changes of intestinal flora in OVX rats by Y1R antagonist
Further, PICRUST was used to analyze the correlation of microbial metabolic function between the three groups. It was found that the metabolism of butyric acid in group OVX was stronger than that in group OVX+BIBO3304, and the function of ion channel was lower than that in group OVX+BIBO3304 (Fig. 5a). However, there was no significant difference in butyric acid metabolism and ion channel function between group OVX+BIBO3304 and group SHAM (Fig. 5b). The results showed that Y1R antagonists are involved in regulating microbial metabolism in butyric acid metabolism and ion channels. 。
Fig. 5 prediction of microbial metabolic function and analysis of functional differences
5. correlation between intestinal flora and bone metabolism parameters
Further analysis of the correlation between microbiota and bone metabolism parameters is shown in Figure 6. Firmicutes They were negatively correlated with bone microstructure parameters (BV/TV, BMD, Tb.N and BS/TV) and serum E2 concentration. Bacteroidetes It was positively correlated with bone microstructure parameters and serum E2 concentration. F/B ratio is also negatively correlated with bone microstructural parameters, indicating that this value represents the degree of maladjustment of various biological processes to a certain extent.
Fig. 6 correlation analysis of intestinal flora and bone metabolism parameters
In conclusion, Y1R antagonists may improve the bone microstructure of OVX rats by downregulating the F/B ratio in the intestinal flora and increasing the content of probiotics. At the same time, the study points out that Y1R antagonist may be a new potential strategy for treating PMO.