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Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model
Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988140/ https://www.ncbi.nlm.nih.gov/pubmed/35399950 http://dx.doi.org/10.3389/fendo.2022.874849 |
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author | Wang, Shanshan Wang, Shengjie Wang, Xiaoning Xu, Yunteng Zhang, Xin Han, Yidan Yan, Hui Liu, Linglong Wang, Lili Ye, Hongzhi Li, Xihai |
author_facet | Wang, Shanshan Wang, Shengjie Wang, Xiaoning Xu, Yunteng Zhang, Xin Han, Yidan Yan, Hui Liu, Linglong Wang, Lili Ye, Hongzhi Li, Xihai |
author_sort | Wang, Shanshan |
collection | PubMed |
description | Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by regulating the bone homeostasis. Thus, we hypothesize that ICA can prevent bone loss by modulating GM and regulating metabolite alterations. The effects of ICA on bone metabolism improvement in ovariectomized (OVX) rats and their relationships with the GM and fecal metabolites were investigated. Micro-computed tomography (micro-CT) and hematoxylin-eosin (HE) staining showed a typical bone boss in OVX group, while ICA or estradiol (E2) administration exhibited positive effects on bone micro-architecture improvement. The GM such as Actinobacteria, Gammaproteobacteria, Erysipelotrichi, Erysipelotrichales, Enterobacteriales, Actinomycetales, Ruminococcus and Oscillospira significantly correlated to serum bone Gla-protein (BGP), receptor activator of nuclear factor-κB (RANK), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate resistant acid phosphatase (TRACP). Further t-test revealed a substantial variation of the GM and fecal metabolites in different treatments. Among them, Lachnoclostridium, Butyricimonas, Rikenella, Paraprevolla, Adlercreutzia, Enterorhabdus, Anaerovorax, Allobaculum, Elusimicrobium, Lactococcus, Globicatella and Lactobacillus were probably the key microbial communities driving the change of bile acid, amino acid and fatty acid, thereby leading to an improvement of PMOP. The significant up-regulation of L-Saccharopine, 1-Aminocyclohexadieneacid and linoleic acid after ICA administration suggested important contributions of amino acid and fatty acid metabolisms in the prevention and treatment of PMOP. Taken together, our study has provided new perspectives to better understand the effects of ICA on PMOP improvement by regulating GM and the associated fecal metabolites. Our findings contribute to develop ICA as a potential therapy for PMOP. |
format | Online Article Text |
id | pubmed-8988140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89881402022-04-08 Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model Wang, Shanshan Wang, Shengjie Wang, Xiaoning Xu, Yunteng Zhang, Xin Han, Yidan Yan, Hui Liu, Linglong Wang, Lili Ye, Hongzhi Li, Xihai Front Endocrinol (Lausanne) Endocrinology Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by regulating the bone homeostasis. Thus, we hypothesize that ICA can prevent bone loss by modulating GM and regulating metabolite alterations. The effects of ICA on bone metabolism improvement in ovariectomized (OVX) rats and their relationships with the GM and fecal metabolites were investigated. Micro-computed tomography (micro-CT) and hematoxylin-eosin (HE) staining showed a typical bone boss in OVX group, while ICA or estradiol (E2) administration exhibited positive effects on bone micro-architecture improvement. The GM such as Actinobacteria, Gammaproteobacteria, Erysipelotrichi, Erysipelotrichales, Enterobacteriales, Actinomycetales, Ruminococcus and Oscillospira significantly correlated to serum bone Gla-protein (BGP), receptor activator of nuclear factor-κB (RANK), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate resistant acid phosphatase (TRACP). Further t-test revealed a substantial variation of the GM and fecal metabolites in different treatments. Among them, Lachnoclostridium, Butyricimonas, Rikenella, Paraprevolla, Adlercreutzia, Enterorhabdus, Anaerovorax, Allobaculum, Elusimicrobium, Lactococcus, Globicatella and Lactobacillus were probably the key microbial communities driving the change of bile acid, amino acid and fatty acid, thereby leading to an improvement of PMOP. The significant up-regulation of L-Saccharopine, 1-Aminocyclohexadieneacid and linoleic acid after ICA administration suggested important contributions of amino acid and fatty acid metabolisms in the prevention and treatment of PMOP. Taken together, our study has provided new perspectives to better understand the effects of ICA on PMOP improvement by regulating GM and the associated fecal metabolites. Our findings contribute to develop ICA as a potential therapy for PMOP. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8988140/ /pubmed/35399950 http://dx.doi.org/10.3389/fendo.2022.874849 Text en Copyright © 2022 Wang, Wang, Wang, Xu, Zhang, Han, Yan, Liu, Wang, Ye and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Wang, Shanshan Wang, Shengjie Wang, Xiaoning Xu, Yunteng Zhang, Xin Han, Yidan Yan, Hui Liu, Linglong Wang, Lili Ye, Hongzhi Li, Xihai Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title | Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title_full | Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title_fullStr | Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title_full_unstemmed | Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title_short | Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model |
title_sort | effects of icariin on modulating gut microbiota and regulating metabolite alterations to prevent bone loss in ovariectomized rat model |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988140/ https://www.ncbi.nlm.nih.gov/pubmed/35399950 http://dx.doi.org/10.3389/fendo.2022.874849 |
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