Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells
Author:
Ma Zongjun1, Liu Yuanyuan2, Shen Wenke2, Yang Jiaxiao2, Wang Ting2, Li Yiwei2, Ma Junbai2, Zhang Xiaoxia2, Wang Hao2
Affiliation:
1. General Hospital of Ningxia Medical University 2. Ningxia Medical University
Abstract
Abstract
Background
Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO.
Methods
A total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants.
Results
The results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, negative regulatory Treg cells and associated IL-10 concentration in peripheral circulation in steoporosis group, but other chronic systemic proinflammatory cytokines and Th17 cells were opposited. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation.
Conclusions
Collectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO.
Publisher
Research Square Platform LLC
Reference42 articles.
1. Pathophysiology of osteoporosis: new mechanistic insights;Armas LA;Endocrinol Metab Clin North Am,2012 2. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis;Fischer V;Semin Cell Dev Biol,2022 3. Menopausal osteoporosis: screening, prevention and treatment;Yong EL;Singap Med J,2021 4. Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes;Tomizawa N;Sci Rep,2020 5. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD, Wang. Nature. 2010;464:59–65. J. A human gut microbial gene catalogue established by metagenomic sequencing.
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