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Chen Y, Xie Y, Yu X. Progress of research on the gut microbiome and its metabolite short-chain fatty acids in postmenopausal osteoporosis: a literature review. Front Med 2025:10.1007/s11684-025-1129-3. [PMID: 40347368 DOI: 10.1007/s11684-025-1129-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 12/16/2024] [Indexed: 05/12/2025]
Abstract
Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease caused by the decrease in estrogen levels after menopause. It leads to bone loss, microstructural damage, and an increased risk of fractures. Studies have found that the gut microbiota and its metabolites can regulate bone metabolism through the gut-bone axis and the gut-brain axis. As research progresses, PMOP has been found to be associated with gut microbiota dysbiosis and Th17/Treg imbalance. The gut microbiota is closely related to the development and differentiation of Treg and Th17 cells. Among them, the metabolites of the gut microbiota such as short-chain fatty acids (SCFAs) can regulate the differentiation of effector T cells by acting on molecular receptors on immune cells, thereby regulating the bone immune process. The multifaceted relationship among the gut microbiota, SCFAs, Th17/Treg cell-mediated bone immunity, and bone metabolism is eliciting attention from researchers. Through a review of existing literature, we have comprehensively summarized the effects of the gut microbiota and SCFAs on PMOP, especially from the perspective of Th17/Treg balance. Regulating this balance may provide new opportunities for PMOP treatment.
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Affiliation(s)
- Yao Chen
- Department of Internal medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
| | - Ying Xie
- Department of Internal medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
| | - Xijie Yu
- Department of Internal medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.
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Zhang Y, Zhu Y, Li M, Zhang M, Shou D, Tong P. A promising approach to diabetic osteoporosis: oxymatrine's effects on gut microbiota and osteoblasts. Nutr Diabetes 2025; 15:19. [PMID: 40328755 PMCID: PMC12055986 DOI: 10.1038/s41387-025-00374-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 04/25/2025] [Accepted: 04/28/2025] [Indexed: 05/08/2025] Open
Abstract
OBJECTIVES Oxymatrine (OMT), a quinolizidine alkaloid derived from Sophora flavescens Ait., has demonstrated therapeutic potential in type 2 diabetes mellitus (T2DM). This study aimed to investigate its effects on diabetic osteoporosis (DOP) and explore the underlying mechanisms involving gut microbiota and osteogenic regulation. METHODS In a rat model of T2DM, intragastric Oxymatrine was used to study trabecular bone repair through bone microstructure and histopathology analyses. Changes in gut microbiota, especially Gram-negative bacteria releasing lipopolysaccharides (LPS), were assessed via 16S rRNA sequencing. miRNA sequencing on LPS-induced rat osteoblasts, with and without Oxymatrine, explored osteoblast proliferation, mineralization, and the miR-539-5p/OGN/Runx2 pathway. RESULTS The administration of OMT resulted in an enhancement of diabetic osteopathy by reversing trabecular bone loss and modifying the composition of gut microbiota, specifically affecting Gram-negative bacteria that release LPS into the bloodstream. miRNA sequencing revealed that miR-539-5p, which was upregulated in LPS-induced ROBs, was downregulated following OMT treatment. Furthermore, OMT was found to promote osteoblast proliferation and mineralization under conditions of LPS exposure and modulate the miR-539-5p/OGN/Runx2 signaling pathway. CONCLUSIONS OMT improves diabetic osteoporosis by altering gut microbiota, decreasing LPS release, and enhancing osteoblast growth and differentiation through the miR-539-5p/OGN/Runx2 pathway, suggesting its potential as a treatment.
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Affiliation(s)
- Yang Zhang
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yiwen Zhu
- The First Clinical School, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Mengying Li
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Minjie Zhang
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Dan Shou
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Peijian Tong
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- The First Clinical School, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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Ma P, Wang R, Chen H, Zheng J, Yang W, Meng B, Liu Y, Lu Y, Zhao J, Gao H. Fecal microbiota transplantation alleviates lipopolysaccharide-induced osteoporosis by modulating gut microbiota and long non-coding RNA TUG1 expression. Front Cell Infect Microbiol 2025; 15:1535666. [PMID: 40292220 PMCID: PMC12021831 DOI: 10.3389/fcimb.2025.1535666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/28/2025] [Indexed: 04/30/2025] Open
Abstract
Purpose To study whether fecal microbiota transplantation (FMT) can alleviate lipopolysaccharide (LPS)-induced osteoporosis (OP) by regulating the composition and abundance of gut microbiota and the expression level of long non-coding RNA (lncRNA) TUG1. Methods Twenty C57BL/6 mice were selected. Two mice were randomly designated as fecal donors, while the remaining mice were randomly divided into control group, LPS group, and LPS + FMT group. Each group consisted of 6 mice. The mice in the LPS and LPS + FMT groups were intraperitoneally injected with LPS to establish the OP model, and the mice in the LPS + FMT group were treated with donor feces by gavage. Micro-CT was used to scan the femur specimens of mice, and the bone structural parameters of the control and LPS groups were compared to verify the effectiveness of the OP model. HE staining was used to compare the microstructure of femurs in the 3 groups. 16S rRNA gene sequencing was used to analyze the composition and abundance of gut microbiota in mice. Immunofluorescence staining was used to compare the expression levels of Runt-related transcription factor 2 (RUNX2) in the femur of the 3 groups. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to compare the expression levels of lncRNA TUG1 in the intestines and serum of mice in the 3 groups. Results Micro-CT showed that compared with the control group, the mice in the LPS group had more bone loss. The bone mineral density, trabecular number, and trabecular thickness of the control group was higher, and the trabecular separation was smaller. The models were validated effectively. HE staining showed that compared with the control group, the bone trabeculae in the LPS group were thinner and sparse, while that in the LPS + FMT group were dense and clear. The 16s rRNA sequencing showed that the abundance of Bacteroides and Lactobacillus in LPS+FMT group was significantly higher than that in LPS group. Immunofluorescence staining showed that the RUNX2 level in the control group and LPS + FMT group was similar, and both were higher than that in the LPS group. The qRT-PCR results showed that the TUG1 mRNA level in the control group and LPS + FMT group was similar and significantly higher than that in the LPS group. Conclusion FMT can enhance osteoblast levels and improve bone structure by modulating the abundance of gut microbiota in OP mice (such as increasing Bacteroides and Lactobacillus populations) and promoting the expression of lncRNA TUG1, thereby alleviating LPS-induced OP.
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Affiliation(s)
- Pengcheng Ma
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Ruoyi Wang
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Huizhi Chen
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Jiachun Zheng
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Weijie Yang
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Bo Meng
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Yifan Liu
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Yao Lu
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Jing Zhao
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China
| | - Hongwei Gao
- Shandong Public Health Clinical Center, Shandong University, Jinan, China
- School of Mechanical Engineering, Shandong University, Jinan, China
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Zhang X, Zhang J, Shen L, Ni B, Wang C. Association between dietary zinc intake amount and prevalence of osteoporosis in middle-aged and elderly individuals: a cross-sectional study. Ir J Med Sci 2025; 194:553-562. [PMID: 39960598 DOI: 10.1007/s11845-025-03910-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 02/08/2025] [Indexed: 04/26/2025]
Abstract
OBJECTIVES This study was aimed to explore the link between dietary zinc intake amount and prevalence of osteoporosis in middle-aged and elderly individuals. METHODS A total of 31,034 participants included in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were detected, and 7355 participants aged ≥ 45 years with integral data were enrolled. Demographic information and dietary intake data were collected via platform of NHANES, and the odds ratio (OR) and 95% confidence interval (CI) of each dietary zinc intake amount tertile category and each unit increase of zinc were analyzed using logistic regression models. Receiver operating characteristic (ROC) curve was applied to determine the optimal cut-off value of dietary zinc intake amount for revealing the prevalence of osteoporosis. RESULTS Of 7355 participants with a mean age of 62.5 ± 11.2 years, 682 participants with osteoporosis were identified, and the dietary zinc intake amount of the osteoporosis group was significantly lower than that of the non-osteoporosis group (P < 0.001). By taking the lowest tertile category as reference category, a higher dietary zinc intake amount was noticed to be positively linked to lower odds for prevalence of osteoporosis. This tendency was not altered in univariate model (P < 0.001), as well as the adjustments for combination of different covariates (Model 1, Model 2, Model 3, and Model 4, P all < 0.05). CONCLUSION This NHANES-based study revealed that a lower dietary zinc intake amount was positively correlated to the prevalence of osteoporosis in middle-aged and elderly individuals among the US population.
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Affiliation(s)
- Xiang Zhang
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, No.1665, Kongjiang Road, Shanghai, 200092, China
| | - Jing Zhang
- Department of Spinal Unit, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, China
| | - Lei Shen
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, No.1665, Kongjiang Road, Shanghai, 200092, China
| | - Binbin Ni
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, No.1665, Kongjiang Road, Shanghai, 200092, China.
| | - Chenglong Wang
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, No.1665, Kongjiang Road, Shanghai, 200092, China.
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Jha SS, Jeyaraman N, Jeyaraman M, Ramasubramanian S, Muthu S, Santos GS, da Fonseca LF, Lana JF. Cross-talks between osteoporosis and gut microbiome. World J Orthop 2025; 16:102274. [PMID: 40124724 PMCID: PMC11924030 DOI: 10.5312/wjo.v16.i3.102274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/06/2025] [Accepted: 02/06/2025] [Indexed: 03/12/2025] Open
Abstract
The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal, playing a crucial role in various physiological functions. These microbes generally live in harmony with the host; however, when dysbiosis occurs, it can contribute to the pathogenesis of diseases, including osteoporosis. Osteoporosis, a systemic skeletal disease characterized by reduced bone mass and increased fracture risk, has attracted significant research attention concerning the role of gut microbes in its development. Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation, modulation of the gut-brain axis, and regulation of the intestinal barrier and nutrient absorption. These microbes can enhance bone mass by inhibiting osteoclast differentiation, inducing apoptosis, reducing bone resorption, and promoting osteoblast proliferation and maturation. Despite these promising findings, the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation. Notably, gut microbiota has been increasingly studied for their potential in early diagnosis, intervention, and as an adjunct therapy for osteoporosis, suggesting a growing utility in improving bone health. Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.
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Affiliation(s)
- Shiva Shankar Jha
- Department of Orthopaedics, Harishchandra Orthopaedic Research Institute, Patna 880023, Bihar, India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Karur 639004, Tamil Nadu, India
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, São Paulo, Brazil
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Ticinesi A, Siniscalchi C, Meschi T, Nouvenne A. Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies. Osteoporos Int 2025; 36:167-191. [PMID: 39643654 DOI: 10.1007/s00198-024-07320-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 11/12/2024] [Indexed: 12/09/2024]
Abstract
The intestinal microbiome is increasingly regarded as a relevant modulator of the pathophysiology of several age-related conditions, including frailty, sarcopenia, and cognitive decline. Aging is in fact associated with alteration of the equilibrium between symbiotic bacteria and opportunistic pathogens, leading to dysbiosis. The microbiome is able to regulate intestinal permeability and systemic inflammation, has a central role in intestinal amino acid metabolism, and produces a large number of metabolites and byproducts, with either beneficial or detrimental consequences for the host physiology. Recent evidence, from both preclinical animal models and clinical studies, suggests that these microbiome-centered pathways could contribute to bone homeostasis, regulating the balance between osteoblast and osteoclast function. In this systematic review, we provide an overview of the mechanisms involved in the gut-bone axis, with a particular focus on microbiome function and microbiome-derived mediators including short-chain fatty acids. We also review the current evidence linking gut microbiota dysbiosis with osteopenia and osteoporosis, and the results of the intervention studies on pre-, pro-, or post-biotics targeting bone mineral density loss in both animal models and human beings, indicating knowledge gaps and highlighting possible avenues for future research.
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Affiliation(s)
- Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy.
- Microbiome Research Hub, University of Parma, Parma, Italy.
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy.
| | - Carmine Siniscalchi
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
| | - Antonio Nouvenne
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
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An F, Jia X, Shi Y, Xiao X, Yang F, Su J, Peng X, Geng G, Yan C. The ultimate microbial composition for correcting Th17/Treg cell imbalance and lipid metabolism disorders in osteoporosis. Int Immunopharmacol 2025; 144:113613. [PMID: 39571271 DOI: 10.1016/j.intimp.2024.113613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/28/2024] [Accepted: 11/07/2024] [Indexed: 12/15/2024]
Abstract
Osteoporosis is a systemic bone disease characterised by decreased bone mass and a deteriorated bone microstructure, leading to increased bone fragility and fracture risk. Disorders of the intestinal microbiota may be key inducers of osteoporosis. Furthermore, such disorders may contribute to osteoporosis by influencing immune function and lipid metabolism. Therefore, in this review, we aimed to summarise the molecular mechanisms through which the intestinal microbiota affect the onset and development of osteoporosis by regulating Th17/Treg imbalance and lipid metabolism disorders. We also discussed the regulatory mechanisms underlying the effect of intestinal microbiota-related modulators on Th17/Treg imbalance and lipid metabolism disorders in osteoporosis, to explore new molecular targets for its treatment and provide a theoretical basis for clinical management.
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Affiliation(s)
- Fangyu An
- Teaching Experiment Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China.
| | - Xueru Jia
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Yangyang Shi
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Xiaolong Xiao
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Fan Yang
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Junchang Su
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Xia Peng
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Guangqin Geng
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Chunlu Yan
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China.
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Wei J, Liu Q, Yuen HY, Lam ACH, Jiang Y, Yang Y, Liu Y, Zhao X, Xiao L. Gut-bone axis perturbation: Mechanisms and interventions via gut microbiota as a primary driver of osteoporosis. J Orthop Translat 2025; 50:373-387. [PMID: 40171106 PMCID: PMC11960541 DOI: 10.1016/j.jot.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 09/27/2024] [Accepted: 11/12/2024] [Indexed: 04/03/2025] Open
Abstract
A growing number of studies have highlighted the significance of human gut microbiota (GM) as a potential target for osteoporosis. In this review, we discuss the effect of GM to bone metabolism focusing on two aspects: the local alterations of the human gut permeability that modify how the GM interact with the gut-bone axis (e.g., intestinal leakage, nutrient absorption), and the alterations of the GM itself (e.g., changes in microbiota metabolites, immune secretion, hormones) that modify the events of the gut-bone axis. We then classify these changes as possible therapeutic targets of bone metabolism and highlight some associated promising microbiome-based therapies. We also extend our discussions into combinatorial treatments that incorporate conservative treatments, such as exercise. We anticipate our review can provide an overview of the current pathophysiological and therapeutic paradigms of the gut-bone axis, as well as the prospects of ongoing clinical trials for readers to gain further insights into better microbiome-based treatments to osteoporosis and other bone-degenerative diseases. The translational potential of this article: This paper reviewed the potential links between gut microbiota and osteoporosis, as well as the prospective therapeutic avenues targeting gut microbiota for osteoporosis management, presenting a thorough and comprehensive literature review.
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Affiliation(s)
- Jingyuan Wei
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
- Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Qi Liu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Ho-Yin Yuen
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Avery Chik-Him Lam
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Yuanyuan Jiang
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
| | - Yuhe Yang
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Yaxiong Liu
- Jihua Laboratory, Foshan, Guangdong, 528000, China
| | - Xin Zhao
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Long Xiao
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
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Gao F, Du Y, Liu H, Ding H, Zhang W, Li Z, Shi B. Maternal supplementation with konjac glucomannan and κ-carrageenan promotes sow performance and benefits the gut barrier in offspring. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 19:272-286. [PMID: 39640556 PMCID: PMC11617309 DOI: 10.1016/j.aninu.2024.05.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/18/2024] [Accepted: 05/10/2024] [Indexed: 12/07/2024]
Abstract
This research aims to investigate the effects of dietary konjac glucomannan and κ-carrageenan (SF) on sow performance and suckling piglet gut barrier. Thirty-four sows in late gestation (parity 2-5) were selected at random and grouped into two treatments. The control group (Con group; n = 17) was fed the basal diet; the SF group was fed the same diet supplemented with 0.25% konjac glucomannan + 0.25% κ-carrageenan (SF group; n = 17). The results showed that sows fed the SF diet had a higher feed intake during lactation than the Con group (P < 0.05), and the levels of neuropeptide tyrosine (NPY) (P = 0.006) and acetylcholine enzyme (AChE) (P < 0.05) significantly increased. The fecal microbial analysis indicated that the SF diet had a higher abundance of Subdoligranulum, Holdemanella, and Succinivibrio at the genus level, and the acetate level was significantly increased (P < 0.05). Moreover, SF lowered the level of interleukin-6 (IL-6) in milk (P < 0.05). Regarding suckling piglets, maternal supplementation with SF reduced jejunal IL-6 protein levels in suckling piglets (P < 0.05). In the colon of the piglet, the SF group up-regulated protein levels of occludin (P < 0.05), and the nuclear factor erythroid 2-related factor 2 (Nrf2) (0.05 ≤ P < 0.1), and claudin 4 (CLDN4) (0.05 ≤ P < 0.1) protein levels tended to be up-regulated. Consequently, supplementation of SF in sow diets positively affects lactation feed intake and maternal microflora. Furthermore, the maternal effect improves the jejunum and colon barriers of suckling piglets.
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Affiliation(s)
- Feng Gao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Yongqing Du
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Haiyang Liu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Hongwei Ding
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Wentao Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Zhongyu Li
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
| | - Baoming Shi
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, Heilongjiang, China
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10
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Wang K, Liu X, Huang H, Suo M, Wang J, Liu X, Zhang J, Chen X, Li Z. A new target for treating intervertebral disk degeneration: gut microbes. Front Microbiol 2024; 15:1452774. [PMID: 39678913 PMCID: PMC11638241 DOI: 10.3389/fmicb.2024.1452774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/16/2024] [Indexed: 12/17/2024] Open
Abstract
Intervertebral disk degeneration (IDD) is a common clinical spinal disease and one of the main causes of low back pain (LBP). Generally speaking, IDD is considered a natural degenerative process with age. However, with the deepening of research, people have discovered that IDD is not only related to age, but also has many factors that can induce and accelerate its progression. In addition, the pathogenesis of IDD remains unclear, resulting in limited traditional treatment methods that cannot effectively prevent and treat IDD. Conservative treatment may lead to patients' dependence on drugs, and the pain relief effect is not obvious. Similarly, surgical treatment is highly invasive, with a longer recovery time and a higher recurrence rate. With the deepening of exploration, people have discovered that intestinal microorganisms are an important symbiotic microbial community in the human body and are closely related to the occurrence and development of various diseases. Changes in intestinal microorganisms and their metabolites may affect the body's inflammatory response, immune regulation, and metabolic processes, thereby affecting the health of the intervertebral disk. In this context, the gut microbiota has received considerable attention as a potential target for delaying or treating IDD. This article first introduces the impact of gut microbes on common distal organs, and then focuses on three potential mechanisms by which gut microbes and their metabolites influence IDD. Finally, we also summarized the methods of delaying or treating IDD by interfering with intestinal microorganisms and their metabolites. Further understanding of the potential mechanisms between intestinal microorganisms and IDD will help to formulate reasonable IDD treatment strategies to achieve ideal therapeutic effects.
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Affiliation(s)
- Kaizhong Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Xiangyan Liu
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Huagui Huang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Moran Suo
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Jinzuo Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Xin Liu
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Jing Zhang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
| | - Xin Chen
- Musculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhonghai Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning, China
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11
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Sevcikova A, Martiniakova M, Omelka R, Stevurkova V, Ciernikova S. The Link Between the Gut Microbiome and Bone Metastasis. Int J Mol Sci 2024; 25:12086. [PMID: 39596154 PMCID: PMC11593804 DOI: 10.3390/ijms252212086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/08/2024] [Accepted: 11/09/2024] [Indexed: 11/28/2024] Open
Abstract
The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.
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Affiliation(s)
- Aneta Sevcikova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, 845 05 Bratislava, Slovakia; (A.S.); (V.S.)
| | - Monika Martiniakova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia;
| | - Radoslav Omelka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia;
| | - Viola Stevurkova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, 845 05 Bratislava, Slovakia; (A.S.); (V.S.)
| | - Sona Ciernikova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, 845 05 Bratislava, Slovakia; (A.S.); (V.S.)
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12
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Huang K, Cai H. The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations - A narrative review. Exp Gerontol 2024; 197:112614. [PMID: 39442896 DOI: 10.1016/j.exger.2024.112614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 10/10/2024] [Accepted: 10/18/2024] [Indexed: 10/25/2024]
Abstract
This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms.
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Affiliation(s)
- Kai Huang
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
| | - Haili Cai
- The 903rd Hospital of People's Liberation Army, Hangzhou 310013, China.
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13
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Li W, Sheng R, Cao M, Rui Y. Exploring the Relationship Between Gut Microbiota and Sarcopenia Based on Gut-Muscle Axis. Food Sci Nutr 2024; 12:8779-8792. [PMID: 39619957 PMCID: PMC11606894 DOI: 10.1002/fsn3.4550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/18/2024] [Accepted: 10/05/2024] [Indexed: 01/04/2025] Open
Abstract
Sarcopenia, as a disease characterized by progressive decline of quality, strength, and function of muscles, has posed an increasingly significant threat to the health of middle-aged and elderly individuals in recent years. With the continuous deepening of studies, the concept of gut-muscle axis has attracted widespread attention worldwide, and the occurrence and development of sarcopenia are believed to be closely related to the composition and functional alterations of gut microbiota. In this review, combined with existing literatures and clinical reports, we have summarized the role and impacts of gut microbiota on the muscle, the relevance between gut microbiota and sarcopenia, potential mechanisms of gut microbiota in the modulation of sarcopenia, potential methods to alleviate sarcopenia by modulating gut microbiota, and relevant advances and perspectives, thus contributing to adding more novel knowledge to this research direction and providing certain reference for future related studies.
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Affiliation(s)
- Wei Li
- Department of Spinal Surgery Unit 1Hanzhong Central Hospital of Shaanxi ProvinceHanzhongShaanxiChina
- Department of OrthopaedicsTianjin Hospital of NingqiangHanzhongShaanxiChina
| | - Ren‐Wang Sheng
- Department of Orthopaedics, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- School of MedicineSoutheast UniversityNanjingJiangsuChina
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- Orthopaedic Trauma Institute (OTI)Southeast UniversityNanjingJiangsuChina
| | - Mu‐Min Cao
- Department of Orthopaedics, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- School of MedicineSoutheast UniversityNanjingJiangsuChina
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- Orthopaedic Trauma Institute (OTI)Southeast UniversityNanjingJiangsuChina
| | - Yun‐Feng Rui
- Department of Orthopaedics, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- School of MedicineSoutheast UniversityNanjingJiangsuChina
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingJiangsuChina
- Orthopaedic Trauma Institute (OTI)Southeast UniversityNanjingJiangsuChina
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14
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Hao L, Yan Y, Huang G, Li H. From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management. Front Cell Infect Microbiol 2024; 14:1416739. [PMID: 39386168 PMCID: PMC11461468 DOI: 10.3389/fcimb.2024.1416739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 09/06/2024] [Indexed: 10/12/2024] Open
Abstract
Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice.
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Affiliation(s)
- Linjie Hao
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yuzhu Yan
- Clinical Laboratory of Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Guilin Huang
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Hui Li
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
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15
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Cao Y, Gao Y, Huang J. Perturbations in gut microbiota composition in osteoporosis: a systematic review and meta-analysis. J Bone Miner Metab 2024; 42:551-563. [PMID: 38864923 DOI: 10.1007/s00774-024-01517-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 05/08/2024] [Indexed: 06/13/2024]
Abstract
INTRODUCTION Osteoporosis (OP) is a chronic bone metabolic disease, which causes a great social and economic burden. The gut microbiota (GM) has become a recent topic of interest in the role of many disease states. Changes in the GM are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial. We performed a mate-analysis to explore and compare the alterations of GM in OP patients. MATERIALS AND METHODS According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, CBM, and Wanfang. In addition, we applied the Stata 17.0 software for data analysis. Bias controls were evaluated with the Newcastle-Ottawa scale (NOS), funnel plot analysis, and Egger's and Begg's tests. RESULTS This research ultimately considered 16 studies, which included the fecal GM data of 2340 people (664 with OP and 1676 healthy controls). The pooled estimate showed an increase of borderline significance on ACE index in patients with OP compared with control participants (SMD = 1.05; 95% CI 0.00-2.10; P = 0.05). There were no significant differences in Chao1, Shannon and Simpson indices. At the phylum level, no significant differences were observed between the OP patients and HCs in the overall analysis. At the genus level, the relative abundance of Blautia presented a decrease of borderline significance between OP and the control group (SMD = - 0.32, 95% CI - 0.65 to - 0.00, P = 0.05). CONCLUSION This systematic review and meta-analysis suggests that patients with OP may exhibit dysbiosis in their gut microbiota, characterized by a reduction in certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacterial populations.
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Affiliation(s)
- Yun Cao
- Department of Traditional Chinese Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Yemei Gao
- Department of Traditional Chinese Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Jiaqin Huang
- Department of Traditional Chinese Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
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16
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Gvozdenović N, Šarac I, Ćorić A, Karan S, Nikolić S, Ždrale I, Milešević J. Impact of Vitamin D Status and Nutrition on the Occurrence of Long Bone Fractures Due to Falls in Elderly Subjects in the Vojvodina Region of Serbia. Nutrients 2024; 16:2702. [PMID: 39203838 PMCID: PMC11356805 DOI: 10.3390/nu16162702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 09/03/2024] Open
Abstract
Bone fractures are a significant public health issue among elderly subjects. This study examines the impact of diet and vitamin D status on the risk of long bone fractures due to falls in elderly subjects in Vojvodina, Serbia. Conducted at the University Clinical Center of Vojvodina in autumn/winter 2022-2023, the study included 210 subjects >65 years: 105 (F: 80/M: 15) with long bone fractures due to falls and 105 (F: 80/M: 15) controls. Groups were similar regarding age and BMI. Dietary intakes (by two 24-h recalls) and serum vitamin D levels were analyzed. The fracture group had a significantly lower median daily vitamin D intake (1.4 μg/day vs. 5.8 μg/day), intake of calcium, energy, proteins, fats, fibers, dairy products, eggs, fish, edible fats/oils, and a higher intake of sweets (p < 0.001 for all). Serum vitamin D levels were significantly lower in the fracture group (40.0 nmol/L vs. 76.0 nmol/L, p < 0.001). Logistic regression identified serum vitamin D as the most important protective factor against fractures, and ROC curve analysis indicated that serum vitamin D levels > 50.5 nmol/L decreased fracture risk. Nutritional improvements (increased intake of vitamin D and protein sources such as fish, eggs, and dairy), increased sun exposure, and routine vitamin D supplementation during winter are advised.
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Affiliation(s)
- Nemanja Gvozdenović
- Faculty of Medicine, University of Novi Sad, 21137 Novi Sad, Serbia; (N.G.); (A.Ć.); (S.K.); (S.N.); (I.Ž.)
- Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of Vojvodina, 21137 Novi Sad, Serbia
| | - Ivana Šarac
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia;
| | - Andrijana Ćorić
- Faculty of Medicine, University of Novi Sad, 21137 Novi Sad, Serbia; (N.G.); (A.Ć.); (S.K.); (S.N.); (I.Ž.)
| | - Saša Karan
- Faculty of Medicine, University of Novi Sad, 21137 Novi Sad, Serbia; (N.G.); (A.Ć.); (S.K.); (S.N.); (I.Ž.)
- Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of Vojvodina, 21137 Novi Sad, Serbia
| | - Stanislava Nikolić
- Faculty of Medicine, University of Novi Sad, 21137 Novi Sad, Serbia; (N.G.); (A.Ć.); (S.K.); (S.N.); (I.Ž.)
- Center of Laboratory Medicine, University Clinical Center of Vojvodina, 21137 Novi Sad, Serbia
| | - Isidora Ždrale
- Faculty of Medicine, University of Novi Sad, 21137 Novi Sad, Serbia; (N.G.); (A.Ć.); (S.K.); (S.N.); (I.Ž.)
| | - Jelena Milešević
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia;
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17
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Feng R, Wang Q, Yu T, Hu H, Wu G, Duan X, Jiang R, Xu Y, Huang Y. Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis. Int Immunopharmacol 2024; 136:112341. [PMID: 38810309 DOI: 10.1016/j.intimp.2024.112341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis. METHODS In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed. RESULTS Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1β, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss. CONCLUSIONS Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.
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Affiliation(s)
- Ruibing Feng
- Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China
| | - Qing Wang
- School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China
| | - Tiantian Yu
- Hubei University of Traditional Chinese Medicine, Wuhan, Hubei Province 430060, PR China
| | - Hao Hu
- Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China; School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China; Hubei University of Traditional Chinese Medicine, Wuhan, Hubei Province 430060, PR China
| | - Gang Wu
- Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China; School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China; Hubei University of Traditional Chinese Medicine, Wuhan, Hubei Province 430060, PR China
| | - Xiaofeng Duan
- Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China
| | - Ruixuan Jiang
- Hubei University of Traditional Chinese Medicine, Wuhan, Hubei Province 430060, PR China
| | - Yifan Xu
- School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China
| | - Yong Huang
- Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China; School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China; Hubei University of Traditional Chinese Medicine, Wuhan, Hubei Province 430060, PR China.
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18
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Srikrishnaraj A, Lanting BA, Burton JP, Teeter MG. The Microbial Revolution in the World of Joint Replacement Surgery. JB JS Open Access 2024; 9:e23.00153. [PMID: 38638595 PMCID: PMC11023614 DOI: 10.2106/jbjs.oa.23.00153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/20/2024] Open
Abstract
Background The prevalence of revision surgery due to aseptic loosening and periprosthetic joint infection (PJI) following total hip and knee arthroplasty is growing. Strategies to prevent the need for revision surgery and its associated health-care costs and patient morbidity are needed. Therapies that modulate the gut microbiota to influence bone health and systemic inflammation are a novel area of research. Methods A literature review of preclinical and clinical peer-reviewed articles relating to the role of the gut microbiota in bone health and PJI was performed. Results There is evidence that the gut microbiota plays a role in maintaining bone mineral density, which can contribute to osseointegration, osteolysis, aseptic loosening, and periprosthetic fractures. Similarly, the gut microbiota influences gut permeability and the potential for bacterial translocation to the bloodstream, increasing susceptibility to PJI. Conclusions Emerging evidence supports the role of the gut microbiota in the development of complications such as aseptic loosening and PJI after total hip or knee arthroplasty. There is a potential for microbial therapies such as probiotics or fecal microbial transplantation to moderate the risk of developing these complications. However, further investigation is required. Clinical Relevance Modulation of the gut microbiota may influence patient outcomes following total joint arthroplasty.
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Affiliation(s)
- Arjuna Srikrishnaraj
- Department of Surgery, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Brent A. Lanting
- Department of Surgery, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
- Bone and Joint Institute, Western University, London, Ontario, Canada
| | - Jeremy P. Burton
- Department of Surgery, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
- Bone and Joint Institute, Western University, London, Ontario, Canada
| | - Matthew G. Teeter
- Department of Surgery, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
- Bone and Joint Institute, Western University, London, Ontario, Canada
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19
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Zhang YW, Wu Y, Liu XF, Chen X, Su JC. Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis. Ageing Res Rev 2024; 94:102196. [PMID: 38218463 DOI: 10.1016/j.arr.2024.102196] [Citation(s) in RCA: 30] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 12/24/2023] [Accepted: 01/09/2024] [Indexed: 01/15/2024]
Abstract
Osteoporosis is a systemic skeletal disease characterized by decreased bone mass, destruction of bone microstructure, raised bone fragility, and enhanced risk of fractures. The correlation between gut microbiota and bone metabolism has gradually become a widespread research hotspot in recent years, and successive studies have revealed that the alterations of gut microbiota and its-related metabolites are related to the occurrence and progression of osteoporosis. Moreover, several emerging studies on the relationship between gut microbiota-related metabolites and bone metabolism are also underway, and extensive research evidence has indicated an inseparable connection between them. Combined with latest literatures and based on inextricable connection of gut-bone axis, this review is aimed to summarize the relation, potential mechanisms, application strategies, clinical application prospects, and existing challenges of gut microbiota and its-related metabolites on osteoporosis, thus updating the knowledge in this research field and providing certain reference for future researches.
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Affiliation(s)
- Yuan-Wei Zhang
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Organoid Research Center, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China
| | - Yan Wu
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Organoid Research Center, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China
| | - Xiang-Fei Liu
- Department of Orthopaedics, Shanghai Zhongye Hospital, Shanghai 200941, China.
| | - Xiao Chen
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China.
| | - Jia-Can Su
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Organoid Research Center, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China.
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20
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Zhang YW, Song PR, Wang SC, Liu H, Shi ZM, Su JC. Diets intervene osteoporosis via gut-bone axis. Gut Microbes 2024; 16:2295432. [PMID: 38174650 PMCID: PMC10773645 DOI: 10.1080/19490976.2023.2295432] [Citation(s) in RCA: 40] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024] Open
Abstract
Osteoporosis is a systemic skeletal disease that seriously endangers the health of middle-aged and older adults. Recently, with the continuous deepening of research, an increasing number of studies have revealed gut microbiota as a potential target for osteoporosis, and the research concept of the gut-bone axis has gradually emerged. Additionally, the intake of dietary nutrients and the adoption of dietary patterns may affect the gut microbiota, and alterations in the gut microbiota might also influence the metabolic status of the host, thus adjusting bone metabolism. Based on the gut-bone axis, dietary intake can also participate in the modulation of bone metabolism by altering abundance, diversity, and composition of gut microbiota. Herein, combined with emerging literatures and relevant studies, this review is aimed to summarize the impacts of different dietary components and patterns on osteoporosis by acting on gut microbiota, as well as underlying mechanisms and proper dietary recommendations.
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Affiliation(s)
- Yuan-Wei Zhang
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- Organoid Research Center, Shanghai University, Shanghai, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
| | - Pei-Ran Song
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- Organoid Research Center, Shanghai University, Shanghai, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
| | - Si-Cheng Wang
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- Organoid Research Center, Shanghai University, Shanghai, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
| | - Han Liu
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- Organoid Research Center, Shanghai University, Shanghai, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
| | - Zhong-Min Shi
- Department of Orthopaedics, Sixth People’s Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jia-Can Su
- Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- Organoid Research Center, Shanghai University, Shanghai, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
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21
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Ruggiero C, Baroni M, Xenos D, Parretti L, Macchione IG, Bubba V, Laudisio A, Pedone C, Ferracci M, Magierski R, Boccardi V, Antonelli-Incalzi R, Mecocci P. Dementia, osteoporosis and fragility fractures: Intricate epidemiological relationships, plausible biological connections, and twisted clinical practices. Ageing Res Rev 2024; 93:102130. [PMID: 38030092 DOI: 10.1016/j.arr.2023.102130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/06/2023] [Accepted: 11/14/2023] [Indexed: 12/01/2023]
Abstract
Dementia, osteoporosis, and fragility fractures are chronic diseases, often co-existing in older adults. These conditions pose severe morbidity, long-term disability, and mortality, with relevant socioeconomic implications. While in the research arena, the discussion remains on whether dementia is the cause or the consequence of fragility fractures, healthcare professionals need a better understanding of the interplay between such conditions from epidemiological and physiological standpoints. With this review, we summarized the available literature surrounding the relationship between cognitive impairment, dementia, and both low bone mineral density (BMD) and fragility fractures. Given the strength of the bi-directional associations and their impact on the quality of life, we shed light on the biological connections between brain and bone systems, presenting the main mediators, including gut microbioma, and pathological pathways leading to the dysregulation of bone and brain metabolism. Ultimately, we synthesized the evidence about the impact of available pharmacological treatments for the prevention of fragility fractures on cognitive functions and individuals' outcomes when dementia coexists. Vice versa, the effects of symptomatic treatments for dementia on the risk of falls and fragility fractures are explored. Combining evidence alongside clinical practice, we discuss challenges and opportunities related to the management of older adults affected by cognitive impairment or dementia and at high risk for fragility fracture prevention, which leads to not only an improvement in patient health-related outcomes and survival but also a reduction in healthcare cost and socio-economic burden.
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Affiliation(s)
- C Ruggiero
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy.
| | - M Baroni
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - D Xenos
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - L Parretti
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - I G Macchione
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - V Bubba
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - A Laudisio
- Department of Medicine, Unit of Geriatrics, Campus Bio-Medico di Roma University, Rome, Italy
| | - C Pedone
- Department of Medicine, Unit of Geriatrics, Campus Bio-Medico di Roma University, Rome, Italy
| | - M Ferracci
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - R Magierski
- Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland
| | - V Boccardi
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
| | - R Antonelli-Incalzi
- Department of Medicine, Unit of Geriatrics, Campus Bio-Medico di Roma University, Rome, Italy
| | - P Mecocci
- Department of Medicine, Section of Gerontology and Geriatrics, University of Perugia, Italy
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22
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Xia WH, Yang CL. Self-reported sleep characteristics are linked to type 2 diabetes in middle-aged and elderly individuals: a cross-sectional study based on NHANES. Ir J Med Sci 2023; 192:2769-2776. [PMID: 36976264 DOI: 10.1007/s11845-023-03352-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023]
Abstract
OBJECTIVE This study was aimed to evaluate the link between sleep characteristics and type 2 diabetes of middle-aged and elderly individuals. METHODS Twenty thousand four hundred ninety-seven individuals enrolled in National Health and Nutritional Examination Survey (NHANES) form periods of 2005-2008 were included in this study, and 3965 individuals aged 45 years and older with complete data were detected. Variables related to sleep characteristics were analyzed by univariate analysis to identify the risk factors of type 2 diabetes, the logistic regression model was used to test for the tendency across the sections of sleep duration, and the link between sleep duration and risk of type 2 diabetes was manifested as odds ratio (OR) and 95% confidence interval (CI). RESULTS Six hundred ninety-four individuals with type 2 diabetes were identified and enrolled in the type 2 diabetes group, while the remaining individuals (n = 3271) were enrolled in the non-type 2 diabetes group. Individuals in the type 2 diabetes group (63.9 ± 10.2) were older than those in the non-type 2 diabetes group (61.2 ± 11.5, P < 0.001). Factors of taking longer time to fall asleep (P < 0.001), sleeping less (≤ 4 h) or more (≥ 9 h) (P < 0.001), having trouble in falling asleep (P = 0.001), frequent snoring (P < 0.001), frequent sleep apnea (P < 0.001), frequent nighttime awakenings (P = 0.004), and frequent excessive daytime sleepiness (P < 0.001) were linked to the risk of type 2 diabetes. CONCLUSION Our study revealed that sleep characteristics were closely linked to type 2 diabetes in middle-aged and elderly individuals, and a longer sleep duration might have protective effects against type 2 diabetes, but it should be constrained within 9 h/night.
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Affiliation(s)
- Wen-Han Xia
- Department of Intensive Care Unit, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi, China
| | - Chun-Li Yang
- Department of Intensive Care Unit, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi, China.
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23
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Hu S, Wan X, Zhu H, Yang H. Structural Characterization and Anti-Osteoporosis Effects of a Novel Sialoglycopeptide from Tuna Eggs. Mar Drugs 2023; 21:573. [PMID: 37999397 PMCID: PMC10672638 DOI: 10.3390/md21110573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/25/2023] Open
Abstract
Several sialoglycopeptides were isolated from several fish eggs and exerted anti-osteoporosis effects. However, few papers have explored sialoglycopeptide from tuna eggs (T-ES). Here, a novel T-ES was prepared through extraction with KCl solution and subsequent enzymolysis. Pure T-ES was obtained through DEAE-Sepharose ion exchange chromatography and sephacryl S-300 gel filtration chromatography. The T-ES was composed of 14.07% protein, 73.54% hexose, and 8.28% Neu5Ac, with a molecular weight of 9481 Da. The backbone carbohydrate in the T-ES was →4)-β-D-GlcN-(1→3)-α-D-GalN-(1→3)-β-D-Glc-(1→2)-α-D-Gal-(1→2)-α-D-Gal-(1→3)-α-D-Man-(1→, with two branches of β-D-GlcN-(1→ and α-D-GalN-(1→ linking at o-4 in →2,4)-α-D-Gal-(1→. Neu5Ac in the T-ES was linked to the branch of α-D-GlcN-(1→. A peptide chain, Ala-Asp-Asn-Lys-Ser*-Met-Ile that was connected to the carbohydrate chain through O-glycosylation at the -OH of serine. Furthermore, in vitro data revealed that T-ES could remarkably enhance bone density, bone biomechanical properties, and bone microstructure in SAMP mice. The T-ES elevated serum osteogenesis-related markers and reduced bone resorption-related markers in serum and urine. The present study's results demonstrated that T-ES, a novel sialoglycopeptide, showed significant anti-osteoporosis effects, which will accelerate the utilization of T-ES as an alternative marine drug or functional food for anti-osteoporosis.
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Affiliation(s)
- Shiwei Hu
- National Engineering Research Center for Maine Aquaculture, Zhejiang Ocean University, Zhoushan 316022, China; (S.H.); (X.W.); (H.Z.)
| | - Xiaofeng Wan
- National Engineering Research Center for Maine Aquaculture, Zhejiang Ocean University, Zhoushan 316022, China; (S.H.); (X.W.); (H.Z.)
| | - Hongli Zhu
- National Engineering Research Center for Maine Aquaculture, Zhejiang Ocean University, Zhoushan 316022, China; (S.H.); (X.W.); (H.Z.)
| | - Huicheng Yang
- Zhejiang Marine Development Research Institute, Zhoushan 316021, China
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24
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Zhivodernikov IV, Kirichenko TV, Markina YV, Postnov AY, Markin AM. Molecular and Cellular Mechanisms of Osteoporosis. Int J Mol Sci 2023; 24:15772. [PMID: 37958752 PMCID: PMC10648156 DOI: 10.3390/ijms242115772] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/26/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, oxidative stress, cellular senescence, and epigenetic factors in the development of bone resorption due to osteoclastogenesis, and decreased mineralization of bone tissue and bone formation due to reduced function of osteoblasts caused by apoptosis and age-depended differentiation of osteoblast precursors into adipocytes. The current review was conducted to describe the basic mechanisms of the development of osteoporosis at molecular and cellular levels and to elucidate the most promising therapeutic strategies of pathogenetic therapy of osteoporosis based on articles cited in PubMed up to September 2023.
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Affiliation(s)
| | | | - Yuliya V. Markina
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia; (I.V.Z.); (T.V.K.); (A.Y.P.); (A.M.M.)
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25
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Morimoto T, Kobayashi T, Kakiuchi T, Esaki M, Tsukamoto M, Yoshihara T, Hirata H, Yabuki S, Mawatari M. Gut-spine axis: a possible correlation between gut microbiota and spinal degenerative diseases. Front Microbiol 2023; 14:1290858. [PMID: 37965563 PMCID: PMC10641865 DOI: 10.3389/fmicb.2023.1290858] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/10/2023] [Indexed: 11/16/2023] Open
Abstract
As society ages, the number of patients with spinal degenerative diseases (SDD) is increasing, posing a major socioeconomic problem for patients and their families. SDD refers to a generic term for degenerative diseases of spinal structures, including osteoporosis (bone), facet osteoarthritis (joint), intervertebral disk degeneration (disk), lumbar spinal canal stenosis (yellow ligament), and spinal sarcopenia (muscle). We propose the term "gut-spine axis" for the first time, given the influence of gut microbiota (GM) on the metabolic, immune, and endocrine environment in hosts through various potential mechanisms. A close cross-talk is noted between the aforementioned spinal components and degenerative diseases. This review outlines the nature and role of GM, highlighting GM abnormalities associated with the degeneration of spinal components. It also summarizes the evidence linking GM to various SDD. The gut-spine axis perspective can provide novel insights into the pathogenesis and treatment of SDD.
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Affiliation(s)
- Tadatsugu Morimoto
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
| | - Takaomi Kobayashi
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
| | - Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Masatsugu Tsukamoto
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
| | - Tomohito Yoshihara
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
| | - Hirohito Hirata
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
| | - Shoji Yabuki
- Fukushima Medical University School of Health Sciences, Fukushima, Japan
| | - Masaaki Mawatari
- Department of Orthopedic Surgery, Faculty of Medicine, Saga University, Saga, Japan
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26
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Zhang S, Ni W. High systemic immune-inflammation index is relevant to osteoporosis among middle-aged and older people: A cross-sectional study. Immun Inflamm Dis 2023; 11:e992. [PMID: 37647432 PMCID: PMC10465993 DOI: 10.1002/iid3.992] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 08/08/2023] [Accepted: 08/11/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND As one of novel inflammatory indexes proposed in recent years, systemic immune-inflammation index (SII) can comprehensively reflect the inflammatory and immune state of the body. This study aims to explore the relationship between SII and osteoporosis among middle-aged and older people. MATERIALS AND METHODS Our study includes 20,497 individuals from National Health and Nutrition Examination Survey (NHANES) 2005-2008, and target study population are confined to people aged 45 years and above. SII is calculated as platelet count × neutrophil count/lymphocyte count. Multivariate logistic regression analysis is used to explore the link between SII and osteoporosis, and receiver operating characteristics curve is used to screen optimal cut-off value of SII for indicating the occurrence of osteoporosis. RESULTS A total of 435 people with osteoporosis are screened among 4625 middle-aged and older people, and individuals in osteoporosis group have higher SII than those in nonosteoporosis group (p = .024). Logistic regression analysis indicates that with the enhancement of SII, prevalence of osteoporosis in each tertile category also increases (p < .001). This tendency is also not changed in univariate model (p < .001), as well as the adjustments for different parameters. Moreover, we also identify that SII of 530.09 is the optimal cut-off value for indicating the occurrence of osteoporosis among middle-aged and older people. CONCLUSIONS This present NHANES-based study noticed that higher SII is positively linked to osteoporosis among middle-aged and older people, and SII should not exceed 530.09 for them to obtain a potentially lower risk of osteoporosis.
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Affiliation(s)
- Suli Zhang
- Department of Operating RoomWujin Hospital Affiliated to Jiangsu University (Wujin People's Hospital)ChangzhouJiangsuChina
- Department of NursingWujin Hospital Affiliated to Jiangsu University (Wujin People's Hospital)ChangzhouJiangsuChina
- Wujin Clinical College of Xuzhou Medical UniversityChangzhouJiangsuChina
| | - Wenyan Ni
- Department of Operating RoomWujin Hospital Affiliated to Jiangsu University (Wujin People's Hospital)ChangzhouJiangsuChina
- Department of NursingWujin Hospital Affiliated to Jiangsu University (Wujin People's Hospital)ChangzhouJiangsuChina
- Wujin Clinical College of Xuzhou Medical UniversityChangzhouJiangsuChina
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27
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Zhang YW, Cao MM, Li YJ, Sheng RW, Zhang RL, Wu MT, Chi JY, Zhou RX, Rui YF. The Preventive Effects of Probiotic Prevotella histicola on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis. Microorganisms 2023; 11:950. [PMID: 37110373 PMCID: PMC10146713 DOI: 10.3390/microorganisms11040950] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/27/2023] [Accepted: 03/30/2023] [Indexed: 04/29/2023] Open
Abstract
It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of Prevotella histicola (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.
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Affiliation(s)
- Yuan-Wei Zhang
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- School of Medicine, Southeast University, Nanjing 210009, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Mu-Min Cao
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- School of Medicine, Southeast University, Nanjing 210009, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Ying-Juan Li
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Ren-Wang Sheng
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- School of Medicine, Southeast University, Nanjing 210009, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Ruo-Lan Zhang
- School of Medicine, Southeast University, Nanjing 210009, China
| | - Meng-Ting Wu
- School of Medicine, Southeast University, Nanjing 210009, China
| | - Jia-Yu Chi
- School of Medicine, Southeast University, Nanjing 210009, China
| | - Rui-Xin Zhou
- School of Medicine, Southeast University, Nanjing 210009, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
- School of Medicine, Southeast University, Nanjing 210009, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
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28
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Zhou RX, Zhang YW, Cao MM, Liu CH, Rui YF, Li YJ. Linking the relation between gut microbiota and glucocorticoid-induced osteoporosis. J Bone Miner Metab 2023; 41:145-162. [PMID: 36912997 PMCID: PMC10010237 DOI: 10.1007/s00774-023-01415-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/27/2023] [Indexed: 03/14/2023]
Abstract
Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.
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Affiliation(s)
- Rui-Xin Zhou
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Yuan-Wei Zhang
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing , Jiangsu, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
| | - Mu-Min Cao
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing , Jiangsu, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
| | - Cun-Hao Liu
- School of Architecture, Southeast University, Nanjing, Jiangsu, China
| | - Yun-Feng Rui
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing , Jiangsu, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
| | - Ying-Juan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China.
- School of Medicine, Southeast University, Nanjing, Jiangsu, China.
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29
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Wu Y, Yang Y, Wang L, Chen Y, Han X, Sun L, Chen H, Chen Q. Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism. Front Endocrinol (Lausanne) 2023; 14:1109296. [PMID: 36967748 PMCID: PMC10034056 DOI: 10.3389/fendo.2023.1109296] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 02/14/2023] [Indexed: 03/11/2023] Open
Abstract
Osteoporosis is a systemic multifactorial bone disease characterized by low bone quality and density and bone microstructure damage, increasing bone fragility and fracture vulnerability. Increased osteoclast differentiation and activity are important factors contributing to bone loss, which is a common pathological manifestation of bone diseases such as osteoporosis. TNF-a/NF-κB is an inflammatory signaling pathway with a key regulatory role in regulating osteoclast formation, and the classical pathway RANKL/RANK/OPG assists osteoclast formation. Activation of this inflammatory pathway promotes the formation of osteoclasts and accelerates the process of osteoporosis. Recent studies and emerging evidence have consistently demonstrated the potential of probiotics to modulate bone health. Secretions of Bifidobacterium, a genus of probiotic bacteria in the phylum Actinobacteria, such as short-chain fatty acids, equol, and exopolysaccharides, have indicated beneficial effects on bone health. This review discusses the molecular mechanisms of the TNF-a/NF-κB inflammatory pathway in regulating osteoclast formation and describes the secretions produced by Bifidobacterium and their potential effects on bone health through this pathway, opening up new directions for future research.
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Affiliation(s)
- Yue Wu
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yunjiao Yang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lan Wang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yiding Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuke Han
- College of Acupuncture & Tuina, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Lisha Sun
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huizhen Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiu Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Qiu Chen,
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