Journal Article

Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells

Ma, Zongjun, Yang, Jiaxiao, Wang, Ting, Ma, Junbai, Zhang, Xiaoxia, Liu, Yuanyuan, Shen, Wenke, Li, Yiwei, Wang, Hao

2024

Overview

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, 17 A, 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, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. 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. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Analysis / Animal models / Blood / Bone mass / Bone turnover / Care and treatment / Cell Movement / Correlation analysis / Cytokines / Cytokines - blood / Diagnosis / Digestive system / Disease / Enzyme-linked immunosorbent assay / Epidemiology / Estrogens / Female / Flow cytometry / Fractures / Gastrointestinal Microbiome - immunology / Gastrointestinal tract / Gut microbiota / Health aspects / Helper cells / Homeostasis / Humans / Immune response / Immune system / Inflammation cytokines / Internal Medicine / Intestinal microflora / Intestine / Leukocyte migration / Lipopolysaccharide (LPS) / Lipopolysaccharides / Lymphocytes / Lymphocytes T / Medicine / Medicine & Public Health / Metabolism / Metabolites / Microbiota / Microbiota (Symbiotic organisms) / Middle Aged / Nutrition and metabolism in musculoskeletal disorders / Orthopedics / Osteoporosis / Osteoporosis, Postmenopausal - blood / Osteoporosis, Postmenopausal - immunology / Osteoporosis, Postmenopausal - microbiology / Ovariectomy / Pathogenesis / Physiological aspects / Plasma / Post-menopause / Postmenopausal osteoporosis (PMO) / Postmenopausal women / Postmenopause - immunology / Regulatory T cells (Treg) / Rehabilitation / Rheumatology / rRNA 16S / Sequence analysis / Sports Medicine / T helper cell 17 (Th17) / T-Lymphocytes, Regulatory - immunology / Th17 Cells - immunology / Womens health