Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats

Abstract

Objective: To investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.

Methods: Thirty female Sprague-Dawley rats were divided into three groups: sham-operation (SHAM) group, OVX group and PTH treatment group. After 3 months of treatment, the femurs, serum and feces were acquired for micro-CT, biochemical analysis and 16S rRNA sequencing, respectively. For 16S rRNA sequencing, after raw reads filtrated and chimera sequences removed, the clean reads were obtained. According to these clean reads, the operational taxonomic units (OTUs) were clustered. Venn diagram analysis was conducted to explore common and unique GM among the three groups. The α-diversity analysis including Shannon and Simpson indexes were used to evaluate the richness and diversity of the GM. The β-diversity analysis was performed to estimate the structure of GM. The metabolic function was predicted by Tax4Fun analysis.

Results: With micro-CT and biochemical analysis, significant improvements were found in the PTH group compared with the OVX group. In Venn diagram analysis, more unique OTUs were found in the SHAM and PTH groups than the OVX group. According to the rank abundance curve, the SHAM and PTH groups had similar richness and evenness, which were higher than the OVX group. Simpson and Shannon indexes were higher in the SHAM and PTH groups compared with the OVX group, indicating that the SHAM and PTH groups had higher microbiota complexity than the OVX group. In β-diversity analysis, apparent separation was found in the OVX group from the PTH and SHAM groups, which suggested that osteoporosis is the critical factor influencing the GM composition and PTH treatment and can restore the structure of GM. Compared with the OVX group, treatment with PTH increased the abundances of GM which were reported to increase bone mass, such as Lactobacillus_reuteri, Muribaculaceae, Ruminococcaceae, and Clostridia, and inhibited the relative abundance of Rikenellaceae, which was reported to be potentially related to osteoporosis. GM function analysis showed that PTH could promote butyrate synthesis. In Tax4Fun analysis, the function of butanoate metabolism is more vital in the PTH group than the OVX and SHAM groups, suggesting PTH treatment could regulate microbial metabolic function, including butanoate metabolism.

Conclusion: Intermittent PTH can interact with GM through increasing the abundance of probiotics and reducing the abundance of the pathogenic bacteria to enhance the bone mass.

Keywords: Bone metabolism; Butyrate; Gut microbiota; Parathyroid hormone; Postmenopausal osteoporosis.