Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis

Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroend...

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Autores principales: Chen, Zhijie, Lv, Mengyuan, Liang, Jing, Yang, Kai, Li, Fan, Zhou, Zhi, Qiu, Minglong, Chen, Haoyi, Cai, Zhengwei, Cui, Wenguo, Li, Zhanchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667841/
https://www.ncbi.nlm.nih.gov/pubmed/37857552
http://dx.doi.org/10.1002/advs.202303015
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author Chen, Zhijie
Lv, Mengyuan
Liang, Jing
Yang, Kai
Li, Fan
Zhou, Zhi
Qiu, Minglong
Chen, Haoyi
Cai, Zhengwei
Cui, Wenguo
Li, Zhanchun
author_facet Chen, Zhijie
Lv, Mengyuan
Liang, Jing
Yang, Kai
Li, Fan
Zhou, Zhi
Qiu, Minglong
Chen, Haoyi
Cai, Zhengwei
Cui, Wenguo
Li, Zhanchun
author_sort Chen, Zhijie
collection PubMed
description Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain‐gut‐bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up‐regulated the expressions of pyroptosis‐related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY‐mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY‐mediated brain‐gut‐bone axis and it might be a novel emerging target to treat PMO.
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spelling pubmed-106678412023-10-19 Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis Chen, Zhijie Lv, Mengyuan Liang, Jing Yang, Kai Li, Fan Zhou, Zhi Qiu, Minglong Chen, Haoyi Cai, Zhengwei Cui, Wenguo Li, Zhanchun Adv Sci (Weinh) Research Articles Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain‐gut‐bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up‐regulated the expressions of pyroptosis‐related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY‐mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY‐mediated brain‐gut‐bone axis and it might be a novel emerging target to treat PMO. John Wiley and Sons Inc. 2023-10-19 /pmc/articles/PMC10667841/ /pubmed/37857552 http://dx.doi.org/10.1002/advs.202303015 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Chen, Zhijie
Lv, Mengyuan
Liang, Jing
Yang, Kai
Li, Fan
Zhou, Zhi
Qiu, Minglong
Chen, Haoyi
Cai, Zhengwei
Cui, Wenguo
Li, Zhanchun
Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title_full Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title_fullStr Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title_full_unstemmed Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title_short Neuropeptide Y‐Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis
title_sort neuropeptide y‐mediated gut microbiota alterations aggravate postmenopausal osteoporosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667841/
https://www.ncbi.nlm.nih.gov/pubmed/37857552
http://dx.doi.org/10.1002/advs.202303015
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