PMID- 31844916 OWN - NLM STAT- MEDLINE DCOM- 20210611 LR - 20210611 IS - 1432-0827 (Electronic) IS - 0171-967X (Linking) VI - 106 IP - 4 DP - 2020 Apr TI - Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats. PG - 444-454 LID - 10.1007/s00223-019-00647-5 [doi] AB - A plethora of evidence has suggested that gut microbiota is involved in the occurrence and development of postmenopausal osteoporosis (PMO). It has been suggested that neuropeptide Y (NPY) modulates the bone metabolism through Y1 receptor (Y1R), and might be associated with gut microbiota. The present study aims to evaluate the anti-osteoporotic effects of Y1R antagonist and to investigate the potential mechanism by which Y1R antagonist regulates gut microbiota. In this study, eighteen female rats were randomly divided into three groups: the sham surgery (SHAM) group, the ovariectomized (OVX) group, and OVX+BIBO3304 group. After 6 weeks following surgery, Y1R antagonist BIBO3304 was administered to the rats in OVX+BIBO3304 group for 7 days. The bone microstructure and serum biochemical parameters were measured at 12 weeks after operation. The differences in the gut microbiota were analyzed by 16S rDNA gene sequencing. Heat-map and Spearman's correlation analyses were constructed to investigate the correlations between microbiota and bone metabolism-related parameters. The results indicated that OVX+BIBO3304 group showed significantly higher BMD, BV/TV, Tb.Th, Tb.N, Conn.D, and serum Ca(2+) level than those in OVX group. Additionally, Y1R antagonist changed the gut microbiota composition with lower Firmicutes/Bacteroidetes ratio and higher proportions of some probiotics, including Lactobacillus. The correlation analysis showed that the changes of gut microbiota were closely associated with bone microstructure and serum Ca(2+) levels. Our results suggested that Y1R antagonist played an anti-osteoporotic effect and regulated gut microbiota in OVX rats, indicating the potential to utilize Y1R antagonist as a novel treatment for PMO. FAU - Xie, Weixin AU - Xie W AD - Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Han, Yi AU - Han Y AD - Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Li, Fan AU - Li F AD - Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Gu, Xiyao AU - Gu X AD - Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Su, Diansan AU - Su D AD - Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Yu, Weifeng AU - Yu W AD - Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. FAU - Li, Zhanchun AU - Li Z AD - Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. lzctgzyyx@163.com. FAU - Xiao, Jie AU - Xiao J AUID- ORCID: 0000-0001-5416-4754 AD - Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 1630 Dongfang Rd, Shanghai, 200127, China. applexiaomz@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191216 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 0 (Neuropeptide Y) RN - 0 (Receptors, Neuropeptide Y) SB - IM MH - Animals MH - Bone Density/drug effects MH - Gastrointestinal Microbiome/*physiology MH - Humans MH - Neuropeptide Y/*metabolism MH - Osteoporosis/*metabolism MH - Osteoporosis, Postmenopausal/metabolism MH - Ovariectomy/*adverse effects/methods MH - Receptors, Neuropeptide Y/*antagonists & inhibitors OTO - NOTNLM OT - Calcium absorption OT - Gut microbiota OT - Neuropeptide Y OT - Osteoporosis OT - Probiotics EDAT- 2019/12/18 06:00 MHDA- 2021/06/12 06:00 CRDT- 2019/12/18 06:00 PHST- 2019/09/16 00:00 [received] PHST- 2019/12/06 00:00 [accepted] PHST- 2019/12/18 06:00 [pubmed] PHST- 2021/06/12 06:00 [medline] PHST- 2019/12/18 06:00 [entrez] AID - 10.1007/s00223-019-00647-5 [pii] AID - 10.1007/s00223-019-00647-5 [doi] PST - ppublish SO - Calcif Tissue Int. 2020 Apr;106(4):444-454. doi: 10.1007/s00223-019-00647-5. Epub 2019 Dec 16.