Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure

ABSTRACTBackground With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lacto...

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Main Authors: Mengyu Guo, Huanjin Liu, Yinting Yu, Xingyu Zhu, Hui Xie, Chenxu Wei, Chunmei Mei, Yun Shi, Nong Zhou, Kunming Qin, Weidong Li
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2023.2190304
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author Mengyu Guo
Huanjin Liu
Yinting Yu
Xingyu Zhu
Hui Xie
Chenxu Wei
Chunmei Mei
Yun Shi
Nong Zhou
Kunming Qin
Weidong Li
author_facet Mengyu Guo
Huanjin Liu
Yinting Yu
Xingyu Zhu
Hui Xie
Chenxu Wei
Chunmei Mei
Yun Shi
Nong Zhou
Kunming Qin
Weidong Li
author_sort Mengyu Guo
collection DOAJ
description ABSTRACTBackground With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.Results We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.Conclusions Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.
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spelling doaj.art-f21c2983421b4d02b9802390978d27482024-03-28T22:38:20ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2190304Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structureMengyu Guo0Huanjin Liu1Yinting Yu2Xingyu Zhu3Hui Xie4Chenxu Wei5Chunmei Mei6Yun Shi7Nong Zhou8Kunming Qin9Weidong Li10School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Pharmacy, Jiangsu Ocean University, Lianyungang, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaABSTRACTBackground With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.Results We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.Conclusions Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.https://www.tandfonline.com/doi/10.1080/19490976.2023.2190304OsteoporosisOVXLactobacillus rhamnosusTh17/Treggut microbiotagut barrier
spellingShingle Mengyu Guo
Huanjin Liu
Yinting Yu
Xingyu Zhu
Hui Xie
Chenxu Wei
Chunmei Mei
Yun Shi
Nong Zhou
Kunming Qin
Weidong Li
Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
Gut Microbes
Osteoporosis
OVX
Lactobacillus rhamnosus
Th17/Treg
gut microbiota
gut barrier
title Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
title_full Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
title_fullStr Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
title_full_unstemmed Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
title_short Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
title_sort lactobacillus rhamnosus gg ameliorates osteoporosis in ovariectomized rats by regulating the th17 treg balance and gut microbiota structure
topic Osteoporosis
OVX
Lactobacillus rhamnosus
Th17/Treg
gut microbiota
gut barrier
url https://www.tandfonline.com/doi/10.1080/19490976.2023.2190304
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