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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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Nami Y, Barghi A, Shahgolzari M, Salehian M, Haghshenas B. Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes. Food Sci Nutr 2025; 13:e4658. [PMID: 39803224 PMCID: PMC11717059 DOI: 10.1002/fsn3.4658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 11/09/2024] [Accepted: 11/25/2024] [Indexed: 01/16/2025] Open
Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. According to the International Society of Sports Nutrition (ISSN), probiotic supplementation can optimize the health, performance, and recovery of athletes at all stages of their careers. Recent research suggests that probiotics can improve immune system functions, reduce gastrointestinal distress, and increase gut permeability in athletes. Additionally, probiotics may provide athletes with secondary health benefits that could positively affect athletic performance through enhanced recovery from fatigue, improved immune function, and maintenance of healthy gastrointestinal tract function. The integration of some probiotic strains into athletes' diets and the consumption of multi-strain compounds may lead to an improvement in performance and can positively affect performance-related aspects such as fatigue, muscle pain, body composition, and cardiorespiratory fitness. In summary, probiotics can be beneficial for athletes at all stages of their careers, from amateur to professional. This paper reviews the progress of research on the role of probiotic supplementation in improving energy metabolism and immune system functions, reducing gastrointestinal distress, and enhancing recovery from fatigue in athletes at different levels.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest and West RegionAgricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)TabrizIran
| | - Anahita Barghi
- Institute of Agricultural Life ScienceDong‐A UniversityBusanSouth Korea
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
- Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Melika Salehian
- Student Research CommitteeKermanshah University of Medical SciencesKermanshahIran
| | - Babak Haghshenas
- Regenerative Medicine Research Center (RMRC), Health Technology InstituteKermanshah University of Medical SciencesKermanshahIran
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Hosain O, Clinkenbeard EL. Adiposity and Mineral Balance in Chronic Kidney Disease. Curr Osteoporos Rep 2024; 22:561-575. [PMID: 39394545 DOI: 10.1007/s11914-024-00884-0] [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] [Accepted: 08/27/2024] [Indexed: 10/13/2024]
Abstract
PURPOSE OF REVIEW Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD. RECENT FINDINGS BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.
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Affiliation(s)
- Ozair Hosain
- Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, 46022, USA
- Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, 46202, USA
| | - Erica L Clinkenbeard
- Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, 46202, USA.
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Chen T, Meng F, Wang N, Hao Y, Fu L. The Characteristics of Gut Microbiota and Its Relation with Diet in Postmenopausal Osteoporosis. Calcif Tissue Int 2024; 115:393-404. [PMID: 39060403 DOI: 10.1007/s00223-024-01260-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: 04/29/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024]
Abstract
The gut microbiome is linked to osteoporosis. Previous clinical studies showed inconsistent results. This study aimed to characterize the gut microbiota feature and reveal its relation with diet in postmenopausal osteoporosis. Fifty-five postmenopausal women with osteoporosis (Op group) and forty-four age-matched postmenopausal women (normal bone mineral density, Con group) were included in this study. Fecal microbiota was collected and analyzed by shallow shotgun sequencing. Food frequency questionnaires were collected from both groups, and Spearman analysis was used to clarify its correlation with gut microbiota. A total of 2671 species from 29 phyla, 292 families, 152 orders, 80 classes were detected in the study. The two groups had no significant difference in the α and β diversity (p > 0.05). At the genus level, Anaerostipes was enriched in Op group (p < 0.05). At species level, Methanobrevibacter smithii, Bifidobacterium animalis, Rhodococcus defluvii, Lactobacillus plantarum, and Carnobacterium mobile were enriched in the Op group, while Bacillus luciferensis, Acetivibrio cellulolyticus, Citrobacter amalonaticus, and Bifidobacterium breve were differentially enriched in the Con group. Food frequency questionnaire showed that postmenopausal women with osteoporosis intaked more red meat, beer, white and red wine (p < 0.05), and the Con group had more yogurt, fruit, and tea consumption. Red meat consumption had a significant negative correlation with Streptosporangiales (p < 0.01) and Actinomadura (p < 0.05). Fruits intake negatively correlated with Nocardiaceae, Rhodococcus, and Rhodococcus defluvii (p < 0.05). More yogurt intake was consistently correlated with a greater abundance of Streptosporangiales. This study suggests that gut microbiota is significantly altered in the postmenopausal osteoporosis population at genus and species levels, and specific dietary intake might relate to these changes.
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Affiliation(s)
- Tinglong Chen
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Fan Meng
- Shanghai Huangpu District Waitan Community Health Service Center, Shanghai, 200011, China
| | - Ning Wang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Yongqiang Hao
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Lingjie Fu
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
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Wu R, Wu J, Jin H, Ma H, Huang H, Xu W, Sun S, Liu X, Dong K, Xie Y, Zeng J, Wang F. Olink and gut microbial metabolomics reveal new biomarkers for the prediction and diagnosis of PMOP. J Bone Miner Metab 2024; 42:503-515. [PMID: 39153113 DOI: 10.1007/s00774-024-01545-z] [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: 03/19/2024] [Accepted: 08/02/2024] [Indexed: 08/19/2024]
Abstract
LNTRODUCTION Postmenopausal osteoporosis (PMOP) can cause postmenopausal women to experience pain and interference. Identifying and exploring potential early diagnostic biomarkers of PMOP is of substantial clinical value and social significance. This study aimed to screen for potential novel diagnostic biomarkers of PMOP through a multiomics approach, providing new directions and ideas for the early prevention and treatment of this disease. MATERIALS AND METHODS Fifteen postmenopausal women with osteoporosis and 12 without were recruited. Clinical information was collected, and various clinical biochemical parameters were tested. Plasma and fecal samples were collected and analyzed using Olink proteomics and gut microbial metabolomics. RESULTS The functions of the differentially abundant metabolites were mainly related to autophagy and arginine and proline metabolism and were involved in immunoinflammatory metabolic processes. Olink showed significant differences in the expression of seven inflammation-related proteins between the two groups. CONCLUSION We demonstrated that metabolic differences between PMOP patients and healthy controls were associated with inflammatory responses and found seven proteins with significant differences. Among these proteins, CDCP1, IL10, and IL-1alpha combined with clinical indicators had high discriminant efficiency in identifying PMOP. This is also the first study to demonstrate noteworthy changes in CDCP1 levels in patients with PMOP.
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Affiliation(s)
- Ruizhe Wu
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Jie Wu
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Hui Jin
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Huaiyu Ma
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Hongxing Huang
- Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Wuji Xu
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Shaoqiu Sun
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Xiaolan Liu
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Kefang Dong
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Yisong Xie
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Jingqi Zeng
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
| | - Fan Wang
- Department of Orthopaedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
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Wang T, Xiong K, He Y, Feng B, Guo L, Gu J, Zhang M, Wang H, Wu X. Chronic pancreatitis-associated metabolic bone diseases: epidemiology, mechanisms, and clinical advances. Am J Physiol Endocrinol Metab 2024; 326:E856-E868. [PMID: 38656128 DOI: 10.1152/ajpendo.00113.2024] [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: 03/19/2024] [Revised: 04/11/2024] [Accepted: 04/17/2024] [Indexed: 04/26/2024]
Abstract
Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.
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Affiliation(s)
- Tianlin Wang
- Department of Emergency, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ke Xiong
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanli He
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Binbin Feng
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - LinBin Guo
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingliang Gu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengrui Zhang
- Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, California, United States
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
| | - Hong Wang
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaohao Wu
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
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Ahire JJ, Kumar V, Rohilla A. Understanding Osteoporosis: Human Bone Density, Genetic Mechanisms, Gut Microbiota, and Future Prospects. Probiotics Antimicrob Proteins 2024; 16:875-883. [PMID: 37874496 DOI: 10.1007/s12602-023-10185-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2023] [Indexed: 10/25/2023]
Abstract
Osteoporosis is a systemic condition of the skeleton that leads to diminished bone mass, a breakdown in the bone tissue's microscopic architecture, and an elevated risk of breaking a bone. The elderly and women particularly after menopause are disproportionately affected, and the condition generally stays undiagnosed until a broken bone causes severe pain and immobility. Causes of osteoporosis include low bone mass, more than normal bone loss, changes in hormone levels (decreased estrogen or testosterone), certain diseases and therapies, and lifestyle factors like smoking and inactivity. The spine, hip, and forearm are particularly vulnerable to osteoporosis-related fractures. The purpose of this article is to present a thorough understanding of osteoporosis, including the disease's connection to bone density in humans, and the major part played by genetic pathways and gut flora. The causes of osteoporosis, the effects of aging on bone density, and why some groups experience a higher incidence of the disease than others are investigated. The paper also includes animal and human experiments investigating the link between gut flora and osteoporosis. Finally, it looks to the future and speculates on possible developments in osteoporosis prevention and therapy.
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Affiliation(s)
- Jayesh J Ahire
- Dr. Reddy's Laboratories Limited, Hyderabad, 500016, India.
| | - Vikram Kumar
- Department of Basic and Applied Sciences, National Institute of Food Technology Entrepreneurship and Management, Sonipat, 131028, India
| | - Alka Rohilla
- Institute of Biology Sciences, Faculty of Science, University of Malaya, 5060, Kuala Lumpur, Malaysia
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Li N, Wang H, Pei H, Wu Y, Li L, Ren Y, Wang S, Ma Y, Luo M, Yuan J, Li L, Qin D. Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis. Front Microbiol 2024; 15:1373013. [PMID: 38835486 PMCID: PMC11148449 DOI: 10.3389/fmicb.2024.1373013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 05/07/2024] [Indexed: 06/06/2024] Open
Abstract
BACKGROUND This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. METHODS We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed. RESULTS A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors. CONCLUSION O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.
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Affiliation(s)
- Ning Li
- First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Haiyang Wang
- First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China
| | - Huan Pei
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Yueying Wu
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Lei Li
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Yu Ren
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Si Wang
- First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Yuan Ma
- The Third People’s Hospital of Yunnan Province, Kunming, China
| | - Miao Luo
- Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China
| | - Jiali Yuan
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
| | - Lvyu Li
- Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China
| | - Dongdong Qin
- Key Laboratory of Integrated Chinese and Western Medicine for Chronic Disease Prevention and Control, Yunnan University of Chinese Medicine, Yunnan Province, Kunming, China
- Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming, China
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Skalny AV, Aschner M, Gritsenko VA, Martins AC, Tizabi Y, Korobeinikova TV, Paoliello MM, Tinkov AA. Modulation of gut microbiota with probiotics as a strategy to counteract endogenous and exogenous neurotoxicity. ADVANCES IN NEUROTOXICOLOGY 2024; 11:133-176. [PMID: 38741946 PMCID: PMC11090489 DOI: 10.1016/bs.ant.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.g., LPS, glucose, Aβ, phospho-tau, α-synuclein) agents. Although the protective mechanisms of probiotic treatments differ between various neurotoxic agents, several key mechanisms at both the intestinal and brain levels seem inherent to all of them. Specifically, probiotic-induced improvement in gut microbiota diversity and taxonomic characteristics results in modulation of gut-derived metabolite production with increased secretion of SFCA. Moreover, modulation of gut microbiota results in inhibition of intestinal absorption of neurotoxic agents and their deposition in brain. Probiotics also maintain gut wall integrity and inhibit intestinal inflammation, thus reducing systemic levels of LPS. Centrally, probiotics ameliorate neurotoxin-induced neuroinflammation by decreasing LPS-induced TLR4/MyD88/NF-κB signaling and prevention of microglia activation. Neuroprotective mechanisms of probiotics also include inhibition of apoptosis and oxidative stress, at least partially by up-regulation of SIRT1 signaling. Moreover, probiotics reduce inhibitory effect of neurotoxic agents on BDNF expression, on neurogenesis, and on synaptic function. They can also reverse altered neurotransmitter metabolism and exert an antiamyloidogenic effect. The latter may be due to up-regulation of ADAM10 activity and down-regulation of presenilin 1 expression. Therefore, in view of the multiple mechanisms invoked for the neuroprotective effect of probiotics, as well as their high tolerance and safety, the use of probiotics should be considered as a therapeutic strategy for ameliorating adverse brain effects of various endogenous and exogenous agents.
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Affiliation(s)
- Anatoly V. Skalny
- Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Medical Elementology, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russia
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Viktor A. Gritsenko
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Airton C. Martins
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Yousef Tizabi
- Department of Pharmacology, Howard University College of Medicine, Washington, DC, United States
| | - Tatiana V. Korobeinikova
- Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Medical Elementology, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russia
| | - Monica M.B. Paoliello
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Alexey A. Tinkov
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
- Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Yaroslavl, Russia
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10
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Chargo NJ, Kang HJ, Das S, Jin Y, Rockwell C, Cho JY, McCabe LR, Parameswaran N. Korean red ginseng extract prevents bone loss in an oral model of glucocorticoid induced osteoporosis in mice. Front Pharmacol 2024; 15:1268134. [PMID: 38533264 PMCID: PMC10963623 DOI: 10.3389/fphar.2024.1268134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 02/20/2024] [Indexed: 03/28/2024] Open
Abstract
The gut microbiota and barrier function play important roles in bone health. We previously demonstrated that chronic glucocorticoid (GC)-induced bone loss in mice is associated with significant shifts in gut microbiota composition and impaired gut barrier function. Korean Red Ginseng (KRG, Panax Ginseng Meyer, Araliaceae) extract has been shown to prevent glucocorticoid-induced osteoporosis (GIO) in a subcutaneous pellet model in mice, but its effect on gut microbiota and barrier function in this context is not known. The overall goal of this study was to test the effect of KRG extract in a clinically relevant, oral model of GIO and further investigate its role in modulating the gut-bone axis. Growing male mice (CD-1, 8 weeks) were treated with 75 μg/mL corticosterone (∼9 mg/kg/day) or 0.4% ethanol vehicle in the drinking water for 4 weeks. During this 4-week period, mice were treated daily with 500 mg/kg/day KRG extract dissolved in sterile water or an equal amount of sterile water via oral gastric gavage. After 4 weeks of treatment, we assessed bone volume, microbiota composition, gut barrier integrity, and immune cells in the bone marrow (BM) and mesenteric lymph nodes (MLNs). 4 weeks of oral GC treatment caused significant distal femur trabecular bone loss, and this was associated with changes in gut microbiota composition, impaired gut barrier function and altered immune cell composition. Importantly, KRG extract prevented distal femur trabecular bone loss and caused significant alterations in gut microbiota composition but had only modest effects on gut barrier function and immune cell populations. Taken together, these results demonstrate that KRG extract significantly modulates the gut microbiota-bone axis and prevents glucocorticoid-induced bone loss in mice.
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Affiliation(s)
- Nicholas J. Chargo
- Department of Physiology, Michigan State University, East Lansing, MI, United States
- College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
| | - Ho Jun Kang
- Department of Physiology, Michigan State University, East Lansing, MI, United States
| | - Subhashari Das
- Department of Physiology, Michigan State University, East Lansing, MI, United States
| | - Yining Jin
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
| | - Cheryl Rockwell
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
| | - Jae Youl Cho
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea
| | - Laura R. McCabe
- Department of Physiology, Michigan State University, East Lansing, MI, United States
- College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
| | - Narayanan Parameswaran
- Department of Physiology, Michigan State University, East Lansing, MI, United States
- College of Human Medicine, Michigan State University, East Lansing, MI, United States
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11
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Abubaker S, Miri S, Mottawea W, Hammami R. Microbial Extracellular Vesicles in Host-Microbiota Interactions. Results Probl Cell Differ 2024; 73:475-520. [PMID: 39242390 DOI: 10.1007/978-3-031-62036-2_19] [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] [Indexed: 09/09/2024]
Abstract
Extracellular vesicles have emerged as key players in cellular communication, influencing various physiological processes and pathophysiological progression, including digestion, immune response, and tissue repairs. Recently, a class of EVs derived from microbial communities has gained significant attention due to their pivotal role in intercellular communication and their potential as biomarkers and biotherapeutic agents. Microbial EVs are membrane-bound molecules encapsulating bioactive metabolites that modulate host physiological and pathological processes. This chapter discusses the evolving history of microbiota-produced EVs, including their discovery, characterization, current research status, and their diverse mechanisms of interaction with other microbes and hosts. This review also highlights the importance of EVs in health and disease and discusses recent research that shows promising results for the therapeutic potential of EVs.
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Affiliation(s)
- Sarah Abubaker
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Saba Miri
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Walid Mottawea
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Riadh Hammami
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.
- Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
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12
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Roberts JL, Chiedo B, Drissi H. Systemic inflammatory and gut microbiota responses to fracture in young and middle-aged mice. GeroScience 2023; 45:3115-3129. [PMID: 37821753 PMCID: PMC10643610 DOI: 10.1007/s11357-023-00963-7] [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: 07/31/2023] [Accepted: 09/25/2023] [Indexed: 10/13/2023] Open
Abstract
Age is a patient-specific factor that can significantly delay fracture healing and exacerbate systemic sequelae during convalescence. The basis for this difference in healing rates is not well-understood, but heightened inflammation has been suggested to be a significant contributor. In this study, we investigated the systemic cytokine and intestinal microbiome response to closed femur fracture in 3-month-old (young adult) and 15-month-old (middle-aged) female wild-type mice. Middle-aged mice had a serum cytokine profile that was distinct from young mice at days 10, 14, and 18 post-fracture. This was characterized by increased concentrations of IL-17a, IL-10, IL-6, MCP-1, EPO, and TNFα. We also observed changes in the community structure of the gut microbiota in both young and middle-aged mice that was evident as early as day 3 post-fracture. This included an Enterobacteriaceae bloom at day 3 post-fracture in middle-aged mice and an increase in the relative abundance of the Muribaculum genus. Moreover, we observed an increase in the relative abundance of the health-promoting Bifidobacterium genus in young mice after fracture that did not occur in middle-aged mice. There were significant correlations between serum cytokines and specific genera, including a negative correlation between Bifidobacterium and the highly induced cytokine IL-17a. Our study demonstrates that aging exacerbates the inflammatory response to fracture leading to high levels of pro-inflammatory cytokines and disruption of the intestinal microbiota.
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Affiliation(s)
- Joseph L Roberts
- Department of Orthopaedics, Emory University School of Medicine, 21 Ortho Ln, 6th Fl, Office 12, Atlanta, GA, 30329, USA.
- The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA.
- College of Health Solutions, Arizona State University, 850 N 5th St, Office 360J, Phoenix, AZ, 85004, USA.
| | - Brandon Chiedo
- The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA
| | - Hicham Drissi
- Department of Orthopaedics, Emory University School of Medicine, 21 Ortho Ln, 6th Fl, Office 12, Atlanta, GA, 30329, USA.
- The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA.
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13
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Biţă CE, Scorei IR, Vreju AF, Muşetescu AE, Mogoşanu GD, Biţă A, Dinescu VC, Dinescu ŞC, Criveanu C, Bărbulescu AL, Florescu A, Ciurea PL. Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1965. [PMID: 38004014 PMCID: PMC10673453 DOI: 10.3390/medicina59111965] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/20/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023]
Abstract
The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.
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Affiliation(s)
- Cristina Elena Biţă
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Ion Romulus Scorei
- Department of Biochemistry, BioBoron Research Institute, S.C. Natural Research S.R.L., 31B Dunării Street, 207465 Podari, Romania
| | - Ananu Florentin Vreju
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Anca Emanuela Muşetescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - George Dan Mogoşanu
- Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (G.D.M.); (A.B.)
| | - Andrei Biţă
- Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (G.D.M.); (A.B.)
| | - Venera Cristina Dinescu
- Department of Health Promotion and Occupational Medicine, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania;
| | - Ştefan Cristian Dinescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Cristina Criveanu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Andreea Lili Bărbulescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Alesandra Florescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
| | - Paulina Lucia Ciurea
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania; (C.E.B.); (A.F.V.); (A.E.M.); (Ş.C.D.); (C.C.); (A.L.B.); (A.F.); (P.L.C.)
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14
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Singh S, Sarma DK, Verma V, Nagpal R, Kumar M. From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1546. [PMID: 37763665 PMCID: PMC10532995 DOI: 10.3390/medicina59091546] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023]
Abstract
The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environmental toxins, and more. They can interfere with bone health through several mechanisms, such as hormonal imbalances, disruptions in bone turnover, direct toxicity to osteoblasts, increased osteoclast activity, immune system aging, impaired inflammatory responses, and disturbances in the gut-bone axis. As a consequence, these disturbances can give rise to a range of bone disorders. The regulation of bone's physiological functions involves an intricate network of continuous processes known as bone remodeling, which is influenced by various intrinsic and extrinsic factors within the organism. However, our understanding of the precise cellular and molecular mechanisms governing the complex interactions between environmental factors and the host elements that affect bone health is still in its nascent stages. In light of this, this comprehensive review aims to explore emerging evidence surrounding bone homeostasis, potential risk factors influencing it, and prospective therapeutic interventions for future management of bone-related disorders.
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Affiliation(s)
- Samradhi Singh
- National Institute for Research in Environmental Health, Bhopal 462030, India; (S.S.); (D.K.S.)
| | - Devojit Kumar Sarma
- National Institute for Research in Environmental Health, Bhopal 462030, India; (S.S.); (D.K.S.)
| | - Vinod Verma
- Stem Cell Research Centre, Department of Hematology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow 226014, India
| | - Ravinder Nagpal
- Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL 32302, USA;
| | - Manoj Kumar
- National Institute for Research in Environmental Health, Bhopal 462030, India; (S.S.); (D.K.S.)
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15
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Santangelo A, Corsello A, Spolidoro GCI, Trovato CM, Agostoni C, Orsini A, Milani GP, Peroni DG. The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications. Nutrients 2023; 15:3680. [PMID: 37686712 PMCID: PMC10489661 DOI: 10.3390/nu15173680] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/10/2023] [Accepted: 08/18/2023] [Indexed: 09/10/2023] Open
Abstract
The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.
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Affiliation(s)
- Andrea Santangelo
- Department of Pediatrics, Santa Chiara Hospital, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (A.S.); (A.O.); (D.G.P.)
| | - Antonio Corsello
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; (G.C.I.S.); (C.A.); (G.P.M.)
| | - Giulia Carla Immacolata Spolidoro
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; (G.C.I.S.); (C.A.); (G.P.M.)
| | - Chiara Maria Trovato
- Hepatology Gastroenterology and Nutrition Unit, Bambino Gesù Children Hospital, 00165 Rome, Italy;
| | - Carlo Agostoni
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; (G.C.I.S.); (C.A.); (G.P.M.)
- Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Alessandro Orsini
- Department of Pediatrics, Santa Chiara Hospital, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (A.S.); (A.O.); (D.G.P.)
| | - Gregorio Paolo Milani
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; (G.C.I.S.); (C.A.); (G.P.M.)
- Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Diego Giampietro Peroni
- Department of Pediatrics, Santa Chiara Hospital, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (A.S.); (A.O.); (D.G.P.)
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16
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Zhang RK, Yan K, Chen HF, Zhang Y, Li GJ, Chen XG, Ge LP, Cheng F, Chen ZN, Yao XM. Anti-osteoporotic drugs affect the pathogenesis of gut microbiota and its metabolites: a clinical study. Front Cell Infect Microbiol 2023; 13:1091083. [PMID: 37475958 PMCID: PMC10354646 DOI: 10.3389/fcimb.2023.1091083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 05/22/2023] [Indexed: 07/22/2023] Open
Abstract
Background Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP. Method In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two. Results After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group (P < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin. Conclusion This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.
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Affiliation(s)
- Rui-kun Zhang
- The Third Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Kun Yan
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hai-feng Chen
- The Third Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yang Zhang
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Gui-jin Li
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xiao-gang Chen
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lin-pu Ge
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Feng Cheng
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Zhi-neng Chen
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xin-miao Yao
- Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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17
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Jin ES, Kim JY, Min J, Jeon SR, Choi KH, Khan SA, Moon GS, Jeong JH. Preliminary Study on Effect of Lactiplantibacillus plantarum on Osteoporosis in the Ovariectomized Rat. Food Sci Anim Resour 2023; 43:712-720. [PMID: 37483997 PMCID: PMC10359845 DOI: 10.5851/kosfa.2023.e29] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/14/2023] [Accepted: 06/14/2023] [Indexed: 07/25/2023] Open
Abstract
Osteoporosis is a growing global health concern primarily associated with decreased estrogen in postmenopausal women. Recently, some strains of probiotics were examined for potential anti-osteoporotic effects. This study intended to evaluate the impacts of Lactiplantibacillus plantarum MGE 3038 strain (MGE 3038) in ovariectomized rats. For this purpose, twelve weeks old female Wistar rats (n=21; 250-300 g) were divided into 3 groups; ovariectomy (OVX) group, OVX/MGE 3038 group and Sham group (control). In these groups; two went through respective OVX and one had daily MGE 3038 administration through oral gavage. Prior to 16 weeks after OVX, we collected blood samples and extracted the tibiae. We scanned the extracted tibiae by in-vivo micro-computed tomography (micro-CT) and evaluated pathology by hematoxylin and eosin (H&E) and Masson's trichrome staining. The serum levels of C-telopeptide of type I collagen (CTX), osteocalcin (OC), and the receptor activator of nuclear factor-ĸB ligand (RANKL) were examined. The OVX/MGE 3038 group showed increases in bone mineral density, trabecular bone volume, trabecular number, and trabecular thickness (Tb.Th), and a decrease in trabecular spacing than the OVX group. However, OVX/MGE 3038 group and control group were measurably comparable in Tb.Th. Micro-CT, H&E, and Masson's trichrome findings exhibited increased preservation and maintenance of trabecular bone structure in the OVX/MGE 3038 group in comparison to the OVX group. In serum, the levels of CTX, OC and RANKL were significantly different between the OVX and OVX/MGE 3038 groups. Taken together, L. plantarum MGE 3038 could be helpful for the treatment of osteoporosis.
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Affiliation(s)
- Eun-Sun Jin
- Department of Internal Medicine, College
of Medicine, Kyung Hee University, Seoul 02447, Korea
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
| | - Ji Yeon Kim
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
| | - JoongKee Min
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
| | - Sang Ryong Jeon
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
- Department of Neurological Surgery, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
| | - Kyoung Hyo Choi
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
- Department of Rehabilitation Medicine,
Asan Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
| | - Shehzad Abid Khan
- 4D Convergence Technology Institute, Korea
National University of Transportation, Jeungpyeong 27909,
Korea
| | - Gi-Seong Moon
- 4D Convergence Technology Institute, Korea
National University of Transportation, Jeungpyeong 27909,
Korea
- Department of Biotechnology, Korea
National University of Transportation, Jeungpyeong 27909,
Korea
| | - Je Hoon Jeong
- Laboratory of Stem Cell Therapy, Asan
Medical Center, College of Medicine, University of Ulsan,
Seoul 05505, Korea
- Department of Neurosurgery, Soonchunhyang
University Bucheon Hospital, Bucheon 14584, Korea
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18
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Roberts JL, Golloshi M, Harding DB, Conduah M, Liu G, Drissi H. Bifidobacterium longum supplementation improves age-related delays in fracture repair. Aging Cell 2023; 22:e13786. [PMID: 36704918 PMCID: PMC10086533 DOI: 10.1111/acel.13786] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/23/2022] [Accepted: 01/09/2023] [Indexed: 01/28/2023] Open
Abstract
Age-related delays in bone repair remains an important clinical issue that can prolong pain and suffering. It is now well established that inflammation increases with aging and that this exacerbated inflammatory response can influence skeletal regeneration. Recently, simple dietary supplementation with beneficial probiotic bacteria has been shown to influence fracture repair in young mice. However, the contribution of the gut microbiota to age-related impairments in fracture healing remains unknown. Here, we sought to determine whether supplementation with a single beneficial probiotic species, Bifidobacterium longum (B. longum), would promote fracture repair in aged (18-month-old) female mice. We found that B. longum supplementation accelerated bony callus formation which improved mechanical properties of the fractured limb. We attribute these pro-regenerative effects of B. longum to preservation of intestinal barrier, dampened systemic inflammation, and maintenance of the microbiota community structure. Moreover, B. longum attenuated many of the fracture-induced systemic pathologies. Our study provides evidence that targeting the gut microbiota using simple dietary approaches can improve fracture healing outcomes and minimize systemic pathologies in the context of aging.
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Affiliation(s)
- Joseph L Roberts
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.,Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Mateo Golloshi
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.,Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Derek B Harding
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.,Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Madison Conduah
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.,Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Guanglu Liu
- Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Hicham Drissi
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.,Atlanta VA Health Care System, Decatur, Georgia, USA
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19
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Song M, Zhang X, Hao G, Lin H, Sun S. Clostridium butyricum Can Promote Bone Development by Regulating Lymphocyte Function in Layer Pullets. Int J Mol Sci 2023; 24:ijms24021457. [PMID: 36674973 PMCID: PMC9867449 DOI: 10.3390/ijms24021457] [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: 12/30/2022] [Revised: 01/07/2023] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Bone health problems are a serious threat to laying hens; microbiome-based therapies, which are harmless and inexpensive, may be an effective solution for bone health problems. Here, we examined the impacts of supplementation with Clostridium butyricum (CB) on bone and immune homeostasis in pullets. The results of in vivo experiments showed that feeding the pullets CB was beneficial to the development of the tibia and upregulated the levels of the bone formation marker alkaline phosphatase and the marker gene runt-related transcription factor 2 (RUNX2). For the immune system, CB treatment significantly upregulated IL-10 expression and significantly increased the proportion of T regulatory (Treg) cells in the spleen and peripheral blood lymphocytes. In the in vitro test, adding CB culture supernatant or butyrate to the osteoblast culture system showed no significant effects on osteoblast bone formation, while adding lymphocyte culture supernatant significantly promoted bone formation. In addition, culture supernatants supplemented with treated lymphocytes (pretreated with CB culture supernatants) stimulated higher levels of bone formation. In sum, the addition of CB improved bone health by modulating cytokine expression and the ratio of Treg cells in the immune systems of layer pullets. Additionally, in vitro CB could promote the bone formation of laying hen osteoblasts through the mediation of lymphocytes.
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Affiliation(s)
- Mengze Song
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai’an 271018, China
| | - Xuesong Zhang
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai’an 271018, China
| | - Guijuan Hao
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai’an 271018, China
| | - Hai Lin
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai’an 271018, China
- Correspondence: (H.L.); (S.S.)
| | - Shuhong Sun
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai’an 271018, China
- Correspondence: (H.L.); (S.S.)
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20
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Fraser D, Ganesan SM. Microbiome, alveolar bone, and metabolites: Connecting the dots. FRONTIERS IN DENTAL MEDICINE 2023. [DOI: 10.3389/fdmed.2022.1074339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
The oral microbiome (OM) is a diverse and dynamic collection of species, separated from alveolar bone by the oral mucosa. Pathogenic shifts in the OM (dysbiosis) during periodontitis are associated with an inflammatory response in the oral mucosa that drives alveolar bone resorption. Alveolar bone is also affected by metabolic disorders such as osteoporosis. Accumulating evidence has linked another microbial community, the gut microbiome (GM), to systemic bone metabolism and osteoporosis. Underlying this connection is the biologic activity of metabolites, byproducts of host and bacterial activity. Limited evidence also suggests that metabolites in the oral cavity signal between the OM and immune system, influencing both alveolar bone homeostasis and pathologic bone destruction in periodontitis. While the oral cavity and gut are connected through the gastrointestinal tract, dissimilar roles for known metabolites between these two niches exemplify the difficulty in translating knowledge on gut-derived metabolites and bone metabolism to alveolar bone. Integrated metabolomic, transcriptomic, and metagenomic approaches hold promise for resolving these challenges and identifying novel metabolites which impact alveolar bone health. Further interrogation through mechanistic testing in pre-clinical models and carefully controlled clinical studies have potential to lead toward translation of these discoveries into meaningful therapies.
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21
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Ibrahim I, Syamala S, Ayariga JA, Xu J, Robertson BK, Meenakshisundaram S, Ajayi OS. Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids. Metabolites 2022; 12:1247. [PMID: 36557285 PMCID: PMC9781427 DOI: 10.3390/metabo12121247] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/30/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
The gut microbiome is a collection of microorganisms and parasites in the gastrointestinal tract. Many factors can affect this community's composition, such as age, sex, diet, medications, and environmental triggers. The relationship between the human host and the gut microbiota is crucial for the organism's survival and development, whereas the disruption of this relationship can lead to various inflammatory diseases. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are used to treat muscle spasticity associated with multiple sclerosis. It is now clear that these compounds also benefit patients with neuroinflammation. CBD and THC are used in the treatment of inflammation. The gut is a significant source of nutrients, including vitamins B and K, which are gut microbiota products. While these vitamins play a crucial role in brain and bone development and function, the influence of gut microbiota on the gut-brain and gut-bone axes extends further and continues to receive increasing scientific scrutiny. The gut microbiota has been demonstrated to be vital for optimal brain functions and stress suppression. Additionally, several studies have revealed the role of gut microbiota in developing and maintaining skeletal integrity and bone mineral density. It can also influence the development and maintenance of bone matrix. The presence of the gut microbiota can influence the actions of specific T regulatory cells, which can lead to the development of bone formation and proliferation. In addition, its metabolites can prevent bone loss. The gut microbiota can help maintain the bone's equilibrium and prevent the development of metabolic diseases, such as osteoporosis. In this review, the dual functions gut microbiota plays in regulating the gut-bone axis and gut-brain axis and the impact of CBD on these roles are discussed.
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Affiliation(s)
- Iddrisu Ibrahim
- The Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Soumyakrishnan Syamala
- Departments of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Joseph Atia Ayariga
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Junhuan Xu
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Boakai K. Robertson
- The Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Sreepriya Meenakshisundaram
- Department of Microbiology and Biotechnology, JB Campus, Bangalore University, Bangalore 560 056, Karnataka, India
| | - Olufemi S. Ajayi
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
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22
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Effect of Administration of Azithromycin and/or Probiotic Bacteria on Bones of Estrogen-Deficient Rats. Pharmaceuticals (Basel) 2022; 15:ph15080915. [PMID: 35893739 PMCID: PMC9331654 DOI: 10.3390/ph15080915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/08/2022] [Accepted: 07/19/2022] [Indexed: 02/04/2023] Open
Abstract
The gut microbiota plays an important role in maintaining homeostasis, including that of the skeletal system. Antibiotics may affect the skeletal system directly or indirectly by influencing the microbiota. Probiotic bacteria have been reported to favorably affect bones in conditions of estrogen deficiency. The aim of this study was to investigate the effects of azithromycin (AZM) administered alone or with probiotic bacteria (Lactobacillus rhamnosus; LR) on bones in estrogen-deficient rats. The experiments were carried out on mature rats divided into five groups: non-ovariectomized (NOVX) control rats, ovariectomized (OVX) control rats, and OVX rats treated with: LR, AZM, or AZM with LR. The drugs were administered for 4 weeks. Serum biochemical parameters, bone mineralization, histomorphometric parameters, and mechanical properties were examined. Estrogen deficiency increased bone turnover and worsened cancellous bone microarchitecture and mechanical properties. The administration of LR or AZM slightly favorably affected some skeletal parameters of estrogen-deficient rats. The administration of AZM with LR did not lead to the addition of the effects observed for the separate treatments, indicating that the effects could be microbiota-mediated.
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23
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Yan Q, Cai L, Guo W. New Advances in Improving Bone Health Based on Specific Gut Microbiota. Front Cell Infect Microbiol 2022; 12:821429. [PMID: 35860378 PMCID: PMC9289272 DOI: 10.3389/fcimb.2022.821429] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 06/01/2022] [Indexed: 12/31/2022] Open
Abstract
The gut microbiota has been shown to play an important role in the pathogenesis of various diseases, including metabolic diseases, cardiovascular diseases, and cancer. Recent studies suggest that the gut microbiota is also closely associated with bone metabolism. However, given the high diversity of the gut microbiota, the effects of different taxa and compositions on bone are poorly understood. Previous studies demonstrated that the mechanisms underlying the effects of the gut microbiota on bone mainly include its modulation of nutrient absorption, intestinal permeability, metabolites (such as short-chain amino acids), immune responses, and hormones or neurotransmitters (such as 5-hydroxytryptamine). Several studies found that external interventions, such as dietary changes, improved bone health and altered the composition of the gut microbiota. This review summarises the beneficial gut bacteria and explores how dietary, natural, and physical factors alter the diversity and composition of the gut microbiota to improve bone health, thereby providing potential new insight into the prevention of osteoporosis.
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Uchida-Fukuhara Y, Hattori T, Fu S, Kondo S, Kuwahara M, Fukuhara D, Islam MM, Kataoka K, Ekuni D, Kubota S, Morita M, Iikegame M, Okamura H. Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction. Microorganisms 2022; 10:microorganisms10051000. [PMID: 35630443 PMCID: PMC9147398 DOI: 10.3390/microorganisms10051000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023] Open
Abstract
To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses’ whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.
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Affiliation(s)
- Yoko Uchida-Fukuhara
- Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (M.I.); (H.O.)
- Correspondence: ; Tel.: +81-86-235-6632; Fax: +81-86-235-6634
| | - Takako Hattori
- Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (T.H.); (S.F.); (S.K.); (M.K.); (S.K.)
| | - Shanqi Fu
- Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (T.H.); (S.F.); (S.K.); (M.K.); (S.K.)
| | - Sei Kondo
- Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (T.H.); (S.F.); (S.K.); (M.K.); (S.K.)
| | - Miho Kuwahara
- Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (T.H.); (S.F.); (S.K.); (M.K.); (S.K.)
| | - Daiki Fukuhara
- Department of Preventive Dentistry, Okayama University Hospital, Okayama 700-0914, Japan;
| | - Md Monirul Islam
- Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (M.M.I.); (K.K.); (D.E.); (M.M.)
| | - Kota Kataoka
- Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (M.M.I.); (K.K.); (D.E.); (M.M.)
| | - Daisuke Ekuni
- Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (M.M.I.); (K.K.); (D.E.); (M.M.)
| | - Satoshi Kubota
- Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (T.H.); (S.F.); (S.K.); (M.K.); (S.K.)
| | - Manabu Morita
- Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (M.M.I.); (K.K.); (D.E.); (M.M.)
| | - Mika Iikegame
- Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (M.I.); (H.O.)
| | - Hirohiko Okamura
- Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (M.I.); (H.O.)
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25
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Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health. Int J Mol Sci 2022; 23:ijms23094748. [PMID: 35563140 PMCID: PMC9102566 DOI: 10.3390/ijms23094748] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/07/2023] Open
Abstract
Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present two new zebrafish transgenic lines containing the coding sequences for fluorescent proteins inserted into the endogenous genes for sp7 and col10a1a with larvae displaying fluorescence in developing osteoblasts and the bone extracellular matrix (mineralized or non-mineralized), respectively. Furthermore, we use these transgenic lines to show that exposure to two different probiotics, Bacillus subtilis and Lactococcus lactis, leads to an increase in osteoblast formation and bone matrix growth and mineralization. Gene expression analysis revealed the effect of the probiotics, particularly Bacillus subtilis, in modulating several skeletal development genes, such as runx2, sp7, spp1 and col10a1a, further supporting their ability to improve bone health. Bacillus subtilis was the more potent probiotic able to significantly reverse the inhibition of bone matrix formation when larvae were exposed to a BMP inhibitor (LDN212854).
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26
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Wang Y, Gao X, Lv J, Zeng Y, Li Q, Wang L, Zhang Y, Gao W, Wang J. Gut Microbiome Signature Are Correlated With Bone Mineral Density Alterations in the Chinese Elders. Front Cell Infect Microbiol 2022; 12:827575. [PMID: 35433497 PMCID: PMC9008261 DOI: 10.3389/fcimb.2022.827575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 03/10/2022] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Osteoporosis (OP), clinically featured with a low bone mineral density (BMD) and high risk of bone fracture, has become a major risk factor of disability and death in the elders, especially in postmenopausal women. The gut microbiome (GM) is thought to be implicated in bone metabolism. Herein, we clarified the composition signature and gene functional profile of GM in older people with normal and low BMD. DESIGN AND METHODS A total of 455 participants underwent the BMD measurement and biochemical detection. GM analysis was further performed on 113 cases of postmenopausal women and men aged over 50, including both 16S rRNA and metagenomic sequencing. RESULTS Generally, the BMD value was significantly lower in the older age groups, especially in the postmenopausal women. Consistently, we observed obvious vitamin D deficiency or insufficiency in females (compared to the male, P < 0.0001). The results from 16S rRNA sequencing revealed higher numbers of OTUs and diversity indexes in females than in males. The abundance in composition of Firmicutes and Clostridiales were correlated with the BMD values in females. LEfSe analysis discovered several enriched bacteria taxons in OP and normal control (NC) subgroups. A positive correlation between the number of genes and BMD values was observed in females based on metagenomic sequencing analysis. Furthermore, we identified the connecting modules among the GM composition - gene functional signature - BMD value/T score in both females and males. CONCLUSIONS This study provides evidences upon which to understand the mechanisms of the effects of GM on bone health, consequently revealing the physiology status and potential diagnostic/therapeutic targets based on GM for OP and postmenopausal osteoporosis (PMOP). Besides, the status of vitamin D deficiency or insufficiency need to be concerned and improved in the Chinese people.
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Affiliation(s)
- Yangyang Wang
- School of Electronics and Information, Northwestern Polytechnical University, Xi’an, China
| | - Xiaoguang Gao
- School of Electronics and Information, Northwestern Polytechnical University, Xi’an, China
| | - Jing Lv
- Clinical Laboratory of Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yuhong Zeng
- Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Qingmei Li
- Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Liping Wang
- Department of Cardiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yuanyuan Zhang
- Department of Cardiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Wenjie Gao
- Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jihan Wang
- Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an, China
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27
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Tesei D, Jewczynko A, Lynch AM, Urbaniak C. Understanding the Complexities and Changes of the Astronaut Microbiome for Successful Long-Duration Space Missions. Life (Basel) 2022; 12:life12040495. [PMID: 35454986 PMCID: PMC9031868 DOI: 10.3390/life12040495] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/17/2022] [Accepted: 03/24/2022] [Indexed: 12/12/2022] Open
Abstract
During space missions, astronauts are faced with a variety of challenges that are unique to spaceflight and that have been known to cause physiological changes in humans over a period of time. Several of these changes occur at the microbiome level, a complex ensemble of microbial communities residing in various anatomic sites of the human body, with a pivotal role in regulating the health and behavior of the host. The microbiome is essential for day-to-day physiological activities, and alterations in microbiome composition and function have been linked to various human diseases. For these reasons, understanding the impact of spaceflight and space conditions on the microbiome of astronauts is important to assess significant health risks that can emerge during long-term missions and to develop countermeasures. Here, we review various conditions that are caused by long-term space exploration and discuss the role of the microbiome in promoting or ameliorating these conditions, as well as space-related factors that impact microbiome composition. The topics explored pertain to microgravity, radiation, immunity, bone health, cognitive function, gender differences and pharmacomicrobiomics. Connections are made between the trifecta of spaceflight, the host and the microbiome, and the significance of these interactions for successful long-term space missions.
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Affiliation(s)
- Donatella Tesei
- Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria;
| | - Anna Jewczynko
- Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada;
| | - Anne M. Lynch
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
- Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Camilla Urbaniak
- ZIN Technologies Inc., Middleburg Heights, OH 44130, USA
- NASA Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA
- Correspondence:
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28
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Lack of berberine effect on bone mechanical properties in rats with experimentally induced diabetes. Pharmacotherapy 2022; 146:112562. [DOI: 10.1016/j.biopha.2021.112562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/08/2021] [Accepted: 12/19/2021] [Indexed: 11/20/2022]
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29
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Li L, Shi Y, Zhao N, Liu Z, Zhao Z, Song Z, Zheng S, Yan M, Leng Z, Chen S, Shang G, Kou H, Liu H. A patient with Turner syndrome received the percutaneous vertebroplasty seven times: a case report and literature review. Eur J Med Res 2021; 26:139. [PMID: 34876225 PMCID: PMC8650291 DOI: 10.1186/s40001-021-00617-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 11/21/2021] [Indexed: 12/19/2022] Open
Abstract
Background Turner syndrome (TS) is characterized as the complete or partial absence of one X chromosome and is an extremely rare disease affecting approximately 1:2500 live female births. Though the prevalence of osteoporosis among women with TS is estimated to be around 55–64% and they suffer more frequently from fractures than normal, few reports concerning TS patients with osteoporosis are able to be seen due to tiny number of patients. Case presentation Here, we report a rare case of TS with osteoporosis, who has undergone percutaneous vertebroplasty (PVP) seven times because of several vertebral compression fractures (VCFs). G-banded karyotype analysis was performed and the result was 45,X[43]/47,XXX[17], indicating that the patient was a mosaicism of TS karyotype and Trisomy X syndrome karyotype. TS is the underlying cause of low level of estrogen for this patient. The interaction of aging, estrogen deficiency and intestinal dysbacteriosis leads to her severe osteoporosis and multi-segmental VCFs. The aim of this report is to provide recommendations regarding the management of TS patients with osteoporosis by reviewing the clinical presentation of TS, the influence of estrogen deficiency in osteoporosis, etc. Conclusions Early diagnosis and hormone replacement treatment are essential for TS patients to prevent osteoporosis and reduce the risk of fractures. This is a rare case report describing TS patient with severe osteoporosis and VCFs.
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Affiliation(s)
- Longyu Li
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Yifang Shi
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Nan Zhao
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Zhengpei Liu
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Zhe Zhao
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Zongmian Song
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Sailei Zheng
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Miaoheng Yan
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Zikuan Leng
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Songfeng Chen
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Guowei Shang
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Hongwei Kou
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China
| | - Hongjian Liu
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China.
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30
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Makarenko OA, Zaderei OV, Maikova HV. Efficacy of using a complex of minerals and vitamins for prevention of complications in bone tissue and the digestive tract in rats with hypothyroidism. REGULATORY MECHANISMS IN BIOSYSTEMS 2021. [DOI: 10.15421/022160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Significant consequences of hypothyroidism are impairments in all types of metabolism, including bone metabolism, pathological changes in the digestive tract and the development of deficiency of vitamins, macro-and micronutrients.The relevance of the study is due to the widespread occurrence of hypothyroidism and the feasibility of developing effective methods for the prevention of the pathology and its complications. The study was aimed at the condition of bone tissue and digestive tract in rats with hypothyroidism, as well as the effectiveness of preventive addition of a complex of vitamins and minerals. The studies were performed on rats with hypothyroidism that was caused using thyrostatic mercazolyl for 50 days, administered orally. Prophylaxis was performed by adding a prophylactic complex of vitamins P, C, D and minerals Ca, Mg, Cu, Se, Mn to the daily diet. In the bone tissue of rats, the indicators of destruction (elastase and acid phosphatase activity) and mineralization (alkaline phosphatase activity, calcium content) as well as the antioxidant state (activities of catalase, glutathione reductase, malonic dialdehyde content) were studied. In the gums and mucous membranes of the digestive tract of rats, we determined indicators of antioxidant status (catalase activity, malonic dialdehydecontent), inflammation (activities of elastase, acid phosphatase) and dysbiosis (activities of urease activity, lysozyme). In the bone tissue of rats with hypothyroidism, activation of destruction processes, reduction of calcium levels, activation of lipid peroxidation and antioxidant enzymes were found. Hypothyroidism also led to pathological disorders in the gums of rats and gastric mucosa, small and large intestine, namely – the development of inflammation, increased membrane permeability, activation of lipid peroxidation, increased contamination with opportunistic bacteria against the background of reduced antioxidant protection. In general, preventive use of the complex contributed to the normalization of the studied parameters in the gums, mucous membranes of the stomach, intestines, as well as remodeling processes and antioxidant-prooxidative state in the bone tissue of animals with hypothyroidism. In the conditions of hypothyroidism, the proposed complex of vitamins and minerals provided notable antioxidant, anti-inflammatory and antidysbiotic effects in the tissues of the gastrointestinal tract, thus overcoming the calcium deficiency in the blood and stopping the destructive and oxidative processes in the bone tissue of animals with hypothyroidism.
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Fabisik M, Tureckova J, Pavliuchenko N, Kralova J, Balounova J, Vicikova K, Skopcova T, Spoutil F, Pokorna J, Angelisova P, Malissen B, Prochazka J, Sedlacek R, Brdicka T. Regulation of Inflammatory Response by Transmembrane Adaptor Protein LST1. Front Immunol 2021; 12:618332. [PMID: 33986741 PMCID: PMC8111073 DOI: 10.3389/fimmu.2021.618332] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 04/08/2021] [Indexed: 12/17/2022] Open
Abstract
LST1 is a small adaptor protein expressed in leukocytes of myeloid lineage. Due to the binding to protein tyrosine phosphatases SHP1 and SHP2 it was thought to have negative regulatory function in leukocyte signaling. It was also shown to be involved in cytoskeleton regulation and generation of tunneling nanotubes. LST1 gene is located in MHCIII locus close to many immunologically relevant genes. In addition, its expression increases under inflammatory conditions such as viral infection, rheumatoid arthritis and inflammatory bowel disease and its deficiency was shown to result in slightly increased sensitivity to influenza infection in mice. However, little else is known about its role in the immune system homeostasis and immune response. Here we show that similar to humans, LST1 is expressed in mice in the cells of the myeloid lineage. In vivo, its deficiency results in alterations in multiple leukocyte subset abundance in steady state and under inflammatory conditions. Moreover, LST1-deficient mice show significant level of resistance to dextran sodium sulphate (DSS) induced acute colitis, a model of inflammatory bowel disease. These data demonstrate that LST1 regulates leukocyte abundance in lymphoid organs and inflammatory response in the gut.
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Affiliation(s)
- Matej Fabisik
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.,Faculty of Science, Charles University, Prague, Czechia
| | - Jolana Tureckova
- Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia.,Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Nataliia Pavliuchenko
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.,Faculty of Science, Charles University, Prague, Czechia
| | - Jarmila Kralova
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
| | - Jana Balounova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Kristina Vicikova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Tereza Skopcova
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
| | - Frantisek Spoutil
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Jana Pokorna
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
| | - Pavla Angelisova
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
| | - Bernard Malissen
- Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, Marseille, France
| | - Jan Prochazka
- Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia.,Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Radislav Sedlacek
- Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia.,Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czechia
| | - Tomas Brdicka
- Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
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