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Ticinesi A, Siniscalchi C, Meschi T, Nouvenne A. Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies. Osteoporos Int 2025; 36:167-191. [PMID: 39643654 DOI: 10.1007/s00198-024-07320-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 11/12/2024] [Indexed: 12/09/2024]
Abstract
The intestinal microbiome is increasingly regarded as a relevant modulator of the pathophysiology of several age-related conditions, including frailty, sarcopenia, and cognitive decline. Aging is in fact associated with alteration of the equilibrium between symbiotic bacteria and opportunistic pathogens, leading to dysbiosis. The microbiome is able to regulate intestinal permeability and systemic inflammation, has a central role in intestinal amino acid metabolism, and produces a large number of metabolites and byproducts, with either beneficial or detrimental consequences for the host physiology. Recent evidence, from both preclinical animal models and clinical studies, suggests that these microbiome-centered pathways could contribute to bone homeostasis, regulating the balance between osteoblast and osteoclast function. In this systematic review, we provide an overview of the mechanisms involved in the gut-bone axis, with a particular focus on microbiome function and microbiome-derived mediators including short-chain fatty acids. We also review the current evidence linking gut microbiota dysbiosis with osteopenia and osteoporosis, and the results of the intervention studies on pre-, pro-, or post-biotics targeting bone mineral density loss in both animal models and human beings, indicating knowledge gaps and highlighting possible avenues for future research.
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Affiliation(s)
- Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy.
- Microbiome Research Hub, University of Parma, Parma, Italy.
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy.
| | - Carmine Siniscalchi
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
| | - Antonio Nouvenne
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Continuity of Care and Multicomplexity, Parma University-Hospital, Parma, Italy
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Beauchemin ET, Hunter C, Maurice CF. Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria. mSphere 2025; 10:e0082524. [PMID: 39723822 PMCID: PMC11774032 DOI: 10.1128/msphere.00825-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 11/15/2024] [Indexed: 12/28/2024] Open
Abstract
The bacteria living in the human gut are essential for host health. Though the composition and metabolism of these bacteria are well described in both healthy hosts and those with intestinal disease, less is known about the metabolic activity of the gut bacteria prior to, and during, disease development-especially regarding gut bacterial replication. Here, we use a recently developed single-cell technique alongside existing metagenomics-based tools to identify, track, and quantify replicating gut bacteria both ex vivo and in situ in the dextran sodium sulfate (DSS) mouse model of colitis. We show that the proportion of replicating gut bacteria decreases when mice have the highest levels of inflammation and returns to baseline levels as mice begin recovering. In addition, we report significant alterations in the composition of the replicating gut bacterial community ex vivo during colitis development. On the taxa level, we observe significant changes in the abundance of taxa such as the mucus-degrading Akkermansia and the poorly described Erysipelatoclostridium genus. We further demonstrate that many taxa exhibit variable replication rates in situ during colitis, including Akkermansia muciniphila. Lastly, we show that colitis development is positively correlated with increases in the presence and abundance of bacteria in situ which are predicted to be fast replicators. This could suggest that taxa with the potential to replicate quickly may have an advantage during intestinal inflammation. These data support the need for additional research using activity-based approaches to further characterize the gut bacterial response to intestinal inflammation and its consequences for both the host and the gut microbial community.IMPORTANCEIt is well known that the bacteria living inside the gut are important for human health. Indeed, the type of bacteria that are present and their metabolism are different in healthy people versus those with intestinal disease. However, less is known about how these gut bacteria are replicating, especially as someone begins to develop intestinal disease. This is particularly important as it is thought that metabolically active gut bacteria may be more relevant to health. Here, we begin to address this gap using several complementary approaches to characterize the replicating gut bacteria in a mouse model of intestinal inflammation. We reveal which gut bacteria are replicating, and how quickly, as mice develop and recover from inflammation. This work can serve as a model for future research to identify how actively growing gut bacteria may be impacting health, or why these particular bacteria tend to thrive during intestinal inflammation.
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Affiliation(s)
- Eve T. Beauchemin
- Department of Microbiology & Immunology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Claire Hunter
- Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, England, United Kingdom
| | - Corinne F. Maurice
- Department of Microbiology & Immunology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
- McGill Centre for Microbiome Research, Montreal, Quebec, Canada
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Huang B, Yin T, Fu S, Liu L, Yang C, Zhou L, Liu X, Zhuang H, Cao Z, Hua Z. Inflammation-oriented montmorillonite adjuvant enhanced oral delivery of anti-TNF-α nanobody against inflammatory bowel disease. Proc Natl Acad Sci U S A 2024; 121:e2320482121. [PMID: 39226349 PMCID: PMC11406300 DOI: 10.1073/pnas.2320482121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 07/02/2024] [Indexed: 09/05/2024] Open
Abstract
Oral delivery of proteins faces challenges due to the harsh conditions of the gastrointestinal (GI) tract, including gastric acid and intestinal enzyme degradation. Permeation enhancers are limited in their ability to deliver proteins with high molecular weight and can potentially cause toxicity by opening tight junctions. To overcome these challenges, we propose the use of montmorillonite (MMT) as an adjuvant that possesses both inflammation-oriented abilities and the ability to regulate gut microbiota. This adjuvant can be used as a universal protein oral delivery technology by fusing with advantageous binding amino acid sequences. We demonstrated that anti-TNF-α nanobody (VII) can be intercalated into the MMT interlayer space. The carboxylate groups (-COOH) of aspartic acid (D) and glutamic acid (E) interact with the MMT surface through electrostatic interactions with sodium ions (Na+). The amino groups (NH2) of asparagine (N) and glutamine (Q) are primarily attracted to the MMT layers through hydrogen bonding with oxygen atoms on the surface. This binding mechanism protects VII from degradation and ensures its release in the intestinal tract, as well as retaining biological activity, leading to significantly enhanced therapeutic effects on colitis. Furthermore, VII@MMT increases the abundance of short-chain fatty acids (SCFAs)-producing strains, including Clostridia, Prevotellaceae, Alloprevotella, Oscillospiraceae, Clostridia_vadinBB60_group, and Ruminococcaceae, therefore enhance the production of SCFAs and butyrate, inducing regulatory T cells (Tregs) production to modulate local and systemic immune homeostasis. Overall, the MMT adjuvant provides a promising universal strategy for protein oral delivery by rational designed protein.
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Affiliation(s)
- Baolian Huang
- School of Biopharmacy, China Pharmaceutical University, Nanjing211198, People’s Republic of China
| | - Te Yin
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
| | - Shuilian Fu
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
| | - Lina Liu
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
| | - Chen Yang
- School of Biopharmacy, China Pharmaceutical University, Nanjing211198, People’s Republic of China
| | - Lulu Zhou
- School of Biopharmacy, China Pharmaceutical University, Nanjing211198, People’s Republic of China
| | - Xing Liu
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
| | - Hongqin Zhuang
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
| | - Zhiting Cao
- School of Biopharmacy, China Pharmaceutical University, Nanjing211198, People’s Republic of China
| | - Zichun Hua
- School of Biopharmacy, China Pharmaceutical University, Nanjing211198, People’s Republic of China
- The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People’s Republic of China
- Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou213164, People’s Republic of China
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Bao X, Ju T, Tollenaar S, Sergi C, Willing BP, Wu J. Ovomucin and its hydrolysates differentially influenced colitis severity in Citrobacter rodentium-infected mice. Food Funct 2024; 15:8496-8509. [PMID: 39056151 DOI: 10.1039/d4fo01813c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Egg white protein ovomucin and its hydrolysates were previously reported to exhibit anti-inflammatory and anti-adhesive activities. However, their potential to regulate pathogen colonization and disease severity has not been fully characterized. To investigate the effects of ovomucin (OVM) and its hydrolysates including ovomucin-Protex 26L (OP) and -pepsin/pancreatin (OPP) on host resistance to pathogen infection, a well-documented colitis model in mice for attaching and effacing E. coli pathogens, Citrobacter rodentium, was used in the current study. C57Bl/6J female mice were fed on a basal diet supplemented with OVM or its hydrolysates for 3 weeks prior to the C. rodentium challenge, with the dietary treatments continued for seven days. Body weight was not affected throughout the experimental period. OP supplementation resulted in lower (P < 0.05) pathogen loads at 7 dpi. Attenuated colitis severity was observed in mice that received OVM and OP, as indicated by reduced colonic pathological scores and pro-inflammatory responses compared with the infected control group. In contrast, OPP consumption resulted in enhanced C. rodentium colonization and disease severity. Notably, reduced microbial diversity indices of the gut microbiota were observed in the OPP-supplemented mice compared with the OVM- and OP-supplemented groups. This study showed the potential of OVM and OP to alleviate the severity of colitis induced by infection while also suggesting the opposite outcome of OPP in mitigating enteric infection.
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Affiliation(s)
- Xiaoyu Bao
- Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada.
| | - Tingting Ju
- Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada.
- Department of Animal Sciences, Purdue University, West Lafayette, IN, USA
| | - Stephanie Tollenaar
- Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada.
| | - Consolato Sergi
- Division of Anatomic Pathology, Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada
| | - Benjamin P Willing
- Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada.
| | - Jianping Wu
- Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada.
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Cao F, Zhang H, Xu B, Li C. Genetic association between gut microbiota and the risk of Guillain-Barré syndrome. J Affect Disord 2024; 357:171-178. [PMID: 38703912 DOI: 10.1016/j.jad.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 04/23/2024] [Accepted: 05/01/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Guillain-Barré Syndrome (GBS) is an autoimmune disease that typically develops after a previous gastrointestinal (GI) infection. However, the exact association between Gut Microbiota (GM) and GBS still remains unknown due to various challenges. This study aimed to investigate the potential causal association between GM and GBS by using a two-sample Mendelian Randomization (TSMR) analysis. METHODS Utilizing the largest available genome-wide association study (GWAS) meta-analysis from the MiBioGen consortium (n = 13,266) as a foundation, we conducted a TSMR to decipher the causal relationship between GM and GBS. Various analytical methods were employed, including the inverse variance weighted (IVW), MR-PRESSO, MR-Egger, and weighted median. The heterogeneity of instrumental variables (IVs) was assessed using Cochran's Q statistics. RESULTS The analysis identified three microbial taxa with a significantly increased risk association for GBS, including Ruminococcus gnavus group (OR = 1.40, 95 % CI: 1.07-1.83), Ruminococcus gauvreauii group (OR = 1.51, 95 % CI: 1.02-2.25), and Ruminococcaceae UCG009 (OR = 1.42, 95 % CI: 1.02-1.97), while Eubacterium brachy group (OR = 1.44, 95 % CI: 1.10-1.87) and Romboutsia (OR = 1.67, 95 % CI: 1.12-2.47) showed a suggestively causal association. On the other hand, Ruminococcaceae UCG004 (OR = 0.61, 95 % CI: 0.41-0.91) had a protective effect on GBS, while Bacilli (OR = 0.60, 95 % CI: 0.38-0.96), Gamma proteobacteria (OR = 0.63, 95 % CI: 0.41-0.98) and Lachnospiraceae UCG001 (OR = 0.69, 95 % CI: 0.49-0.96) showed a suggestively protective association for GBS. CONCLUSION The MR analysis suggests a potential causal relationship between specific GM taxa and the risk of GBS. However, further extensive research involving diversified populations is imperative to validate these findings.
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Affiliation(s)
- Fangzheng Cao
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China; The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Houwen Zhang
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China; The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Xu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China; Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Chunrong Li
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
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Saeki C, Saito M, Tsubota A. Association of chronic liver disease with bone diseases and muscle weakness. J Bone Miner Metab 2024; 42:399-412. [PMID: 38302761 DOI: 10.1007/s00774-023-01488-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 11/16/2023] [Indexed: 02/03/2024]
Abstract
The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Mitsuru Saito
- Department of Orthopedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
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Ma Q, Wen X, Xu G. The causal association of specific gut microbiota on the risk of membranous nephropathy: a Mendelian randomization study. Int Urol Nephrol 2024; 56:2021-2030. [PMID: 38180581 DOI: 10.1007/s11255-023-03926-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 12/18/2023] [Indexed: 01/06/2024]
Abstract
PURPOSE Gut microbiota transplantation has been reported to improve the renal function of membranous nephropathy (MN). However, whether there is a causal effect of gut microbiota on MN remained unclear. METHODS We performed two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used as the main approach to evaluate the causal relationship between gut microbiota and MN. Additional methods including MR-Egger regression, weighted median, and MR-weighted mode were also conducted. Cochrane's Q test, MR-Egger regression, and MR-PRESSO were employed to detect heterogeneity and pleiotropy, respectively. RESULTS A total of 196 gut microbiota were examined. After IVW and sensitivity analysis, eight gut bacteria taxa were observed causal effects on the risk of MN. Specifically, Genus. Oscillibacter was a protective factor (OR: 0.57; 95% CI 0.328-0.979; P = 0.042), while Class. Melainabacteria (OR: 1.51; 95% CI 1.004-2.277; P = 0.048), Genus. Butyricicoccus (OR: 2.16; 95% CI 1.005-4.621; P = 0.048), Genus. Catenibacterium (OR: 1.49; 95% CI 1.043-2.134; P = 0.028), Genus.Ruminiclostridium5 (OR: 1.74; 95% CI 1.053-2.862; P = 0.030), Genus. Ruminococcaceae UCG-003 (OR: 1.73; 95% CI 1.110-2.692; P = 0.015), Order. Bacillales (OR: 1.52; 95% CI 1.135-2.025; P = 0.0048) and Order. Gastranaerophilales (OR: 1.45; 95% CI 1.010-2.085; P = 0.044) were risk factors. Heterogeneity was not significant for most single-nucleotide polymorphisms, and no statistical difference in pleiotropy. CONCLUSIONS This study first indicated the causal association between specific gut microbiota and MN, which would be of great significance to guide clinical prevention and treatment in MN.
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Affiliation(s)
- Qiqi Ma
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Xiaoli Wen
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, 330006, People's Republic of China.
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Cheng X, Cheng B, Jin R, Zheng H, Zhou J, Shan S. The role of circulating metabolites and gut microbiome in hypertrophic scar: a two-sample Mendelian randomization study. Arch Dermatol Res 2024; 316:315. [PMID: 38822918 DOI: 10.1007/s00403-024-03116-8] [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: 04/02/2024] [Revised: 04/02/2024] [Accepted: 04/26/2024] [Indexed: 06/03/2024]
Abstract
Hypertrophic scarring is a fibro-proliferative disorder caused by abnormal cutaneous wound healing. Circulating metabolites and the gut microbiome may be involved in the formation of these scars, but high-quality evidence of causality is lacking. To assess whether circulating metabolites and the gut microbiome contain genetically predicted modifiable risk factors for hypertrophic scar formation. Two-sample Mendelian randomization (MR) was performed using MR-Egger, inverse-variance weighting (IVW), Mendelian Randomization Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median methods. Based on the genome-wide significance level, genetically predicted uridine (P = 0.015, odds ratio [OR] = 1903.514, 95% confidence interval [CI] 4.280-846,616.433) and isovalerylcarnitine (P = 0.039, OR = 7.765, 95% CI 1.106-54.512) were positively correlated with hypertrophic scar risk, while N-acetylalanine (P = 0.013, OR = 7.98E-10, 95% CI 5.19E-17-0.012) and glycochenodeoxycholate (P = 0.021, OR = 0.021 95% CI 0.003-0.628) were negatively correlated. Gastranaerophilales and two unknown gut microbe species (P = 0.031, OR = 0.378, 95% CI 0.156-0.914) were associated with an decreased risk of hypertrophic scarring. Circulating metabolites and gut microbiome components may have either positive or negative causal effects on hypertrophic scar formation. The study provides new insights into strategies for diagnosing and limiting hypertrophic scarring.
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Affiliation(s)
- Xinwei Cheng
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Bin Cheng
- Department of Burns and Plastic Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, Guangdong, China
| | - Rui Jin
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Hongkun Zheng
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Jia Zhou
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
| | - Shengzhou Shan
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
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Xiao H, Wang Y, Chen Y, Chen R, Yang C, Geng B, Xia Y. Gut-bone axis research: unveiling the impact of gut microbiota on postmenopausal osteoporosis and osteoclasts through Mendelian randomization. Front Endocrinol (Lausanne) 2024; 15:1419566. [PMID: 38883609 PMCID: PMC11176613 DOI: 10.3389/fendo.2024.1419566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 05/17/2024] [Indexed: 06/18/2024] Open
Abstract
Background Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention. Methods We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287. Results The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis. Conclusion This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.
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Affiliation(s)
- Hefang Xiao
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Yaobin Wang
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Yi Chen
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Rongjin Chen
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Chenhui Yang
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Bin Geng
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
| | - Yayi Xia
- Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China
- Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, China
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Wang J, Liu S, Ma J, Dong X, Long S, Piao X. Growth performance, serum parameters, inflammatory responses, intestinal morphology and microbiota of weaned piglets fed 18% crude protein diets with different ratios of standardized ileal digestible isoleucine to lysine. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 16:313-325. [PMID: 38362516 PMCID: PMC10867559 DOI: 10.1016/j.aninu.2023.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 11/24/2023] [Accepted: 11/30/2023] [Indexed: 02/17/2024]
Abstract
The present study was to explore the Ile requirement of piglets fed 18% crude protein (CP) diets. Two hundred and fifty 28-day-old Duroc × Landrace × Yorkshire piglets (8.37 ± 1.92 kg) were randomly divided into 5 dietary treatments (10 piglets per replicate, 5 barrows and 5 gilts per replicate) with 45%, 50%, 55%, 60%, 65% standardized ileal digestible (SID) Ile-to-Lys ratios, and the SID Lys was formulated to 1.19%. The experimental design consisted of two phases (d 1 to 14 and d 15 to 28). Results showed that average daily gain (ADG) had a tendency to quadratically increase as the SID Ile-to-Lys ratio increased (P = 0.09), and the optimum SID Ile-to-Lys ratios required to maximize ADG were 48.33% and 54.63% for broken-line linear model and quadratic polynomial model, respectively. Different SID Ile-to-Lys ratios had no significant effects on average daily feed intake and gain-to-feed ratio. Dry matter (P < 0.01), CP (P = 0.01), ether extract (P = 0.04), gross energy (P < 0.01) and organic matter (P < 0.01) digestibility increased quadratically. Serum total cholesterol levels decreased linearly (P = 0.01) and quadratically (P < 0.01); aspartate aminotransferase (P < 0.01), interleukin-1β (P = 0.01), and tumor necrosis factor-α (P < 0.01) levels decreased quadratically; immunoglobulin G (P = 0.03) and immunoglobulin M (P = 0.01) concentrations increased quadratically. Serum Ser levels decreased linearly (P < 0.01) and quadratically (P = 0.01); Glu (P = 0.02), Arg (P = 0.05), and Thr (P = 0.03) levels decreased quadratically; Gly (P < 0.01) and Leu (P = 0.01) levels decreased linearly; Ile (P < 0.01) concentration increased linearly. Duodenal villus height (P < 0.01) and villus height to crypt depth ratio (P < 0.01) increased quadratically. The deficiency or excess of Ile decreased short chain fatty acid-producing bacteria abundance and increased pathogenic bacteria abundance. Overall, taking ADG as the effect index, the optimum SID Ile-to-Lys ratios of piglets offered 18% CP diets were 48.33% and 54.63% based on two different statistical models, respectively, and the deficiency or excess of lle negatively affected piglet growth rates and health status.
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Affiliation(s)
- Jian Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Sujie Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Jiayu Ma
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Xiaoli Dong
- CJ International Trading Co., Ltd, Shanghai 201107, China
| | - Shenfei Long
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Xiangshu Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
- Beijing Jingwa Agricultural Science and Technology Innovation Center, Beijing, 101206, China
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Skoracka K, Hryhorowicz S, Tovoli F, Raiteri A, Rychter AM, Słomski R, Dobrowolska A, Granito A, Krela-Kaźmierczak I. Genetic, Immunological, Dietary, Gut Microbiota, and Environmental Determinants of Osteoporosis in the Course of Celiac Disease: Which Factor Plays the First Violin in This Orchestra? Calcif Tissue Int 2024; 114:98-109. [PMID: 38049681 PMCID: PMC10803478 DOI: 10.1007/s00223-023-01155-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 10/24/2023] [Indexed: 12/06/2023]
Abstract
Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The worldwide prevalence of CD is estimated to be 0.7-1.4% of the general population. Etiopathology of this disease is multifactorial, with genetic determinants being a major contributing player to CD susceptibility. Its manifestation embraces different organs, including the musculoskeletal apparat. Patients with CD have increased risk of bone disorders. According to data, bone disorders - osteopenia and osteoporosis - can affect up to 70% of patients with CD at diagnosis, and it decreases after the initiation of a gluten-free diet. Gluten consumption in patients with CD triggers an inflammatory reaction followed by tissue damage, and both; local and systemic inflammation can increase the risk of bone mass deterioration. Other theory assumes shortages of vitamin D and an impaired calcium absorption mechanism leading to secondary hyperparathyroidism. Taking into account the increasing prevalence of CD and osteoporosis, we broadly discuss genetic, immunological, dietary, gut microbiota, and environmental factors that could increase the risk of osteoporosis in CD. Furthermore, we discuss lifestyle and pharmacological preventing and treatment measures.
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Affiliation(s)
- Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 49 Przybyszewski Street, 60-355, Poznan, Poland.
- Doctoral School, Poznan University of Medical Sciences, Fredry St. 10, 61-701, Poznan, Poland.
| | - Szymon Hryhorowicz
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alberto Raiteri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 49 Przybyszewski Street, 60-355, Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, Fredry St. 10, 61-701, Poznan, Poland
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 49 Przybyszewski Street, 60-355, Poznan, Poland
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 49 Przybyszewski Street, 60-355, Poznan, Poland
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Liang X, Wang Z, Shu Q, Huang X, Wang J, Wu J, Liu N, Xie N. A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for primary sclerosing cholangitis. Eur J Gastroenterol Hepatol 2024; 36:147-154. [PMID: 38131422 DOI: 10.1097/meg.0000000000002666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
BACKGROUND Previous studies indicate that gut microbiota correlates to primary sclerosing cholangitis (PSC), but the causation is still unclear. We sought to reveal the causal relationship between gut microbiota and PSC with a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS The large-scale genome-wide association study (GWAS) summary statistics and a bidirectional two-sample MR study were used to assess the causality between gut microbiota and PSC. Multiple sensitivity analyses were used to identify the robustness of our results. RESULTS Three microbial taxa causally correlated to PSC. Genus Ruminococcaceae UCG002 (OR: 1.855, 95% CI: 1.068-3.220, P = 0.028) increased the risk of PSC. Class Betaproteobacteria (OR: 0.360, 95% CI: 0.171-0.758, P = 0.007), and genus Ruminiclostridium6 (OR: 0.474, 95% CI: 0.219-0.820, P = 0.011) had protective effects on PSC. In addition, we found the causal relationship of PSC with higher abundance of genus Dialister (beta: 0.059, 95% CI: 0.017-0.102, P = 0.006), genus Veillonella (beta: 0.065, 95% CI: 0.016-0.113, P = 0.009), class Melainabacteria (beta: 0.073, 95% CI: 0.012-0.133, P = 0.019), and order Gastranaerophilales (beta: 0.072, 95% CI: 0.011-0.113, P = 0.133). CONCLUSION Our study reveals the causality between gut microbiota and PSC, providing new insights into the pathological mechanisms of PSC and facilitating the development of novel biomarkers and disease-modifying therapeutics for PSC from the perspective of gut microbiota.
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Affiliation(s)
- Xiru Liang
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
| | - Ziwei Wang
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
| | - Qiuai Shu
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
| | - Xindi Huang
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
| | - Jinhai Wang
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
| | - Jian Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University
| | - Na Liu
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Ning Xie
- Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Shen C, Chen Z, Zhang W, Chen X, Zheng B, Shi C. Preliminary study of the effect of gut microbiota on the development of prostatitis. BMC Med Genomics 2024; 17:35. [PMID: 38273299 PMCID: PMC10809527 DOI: 10.1186/s12920-024-01812-y] [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: 08/25/2023] [Accepted: 01/19/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Dysbacteriosis of intestinal tract may cause systemic inflammation, making distant anatomical locations more susceptible to illness. Recent research has demonstrated that the microbiome can affect both prostatitis and the inflammation of the prostate that is linked to prostate cancer. It is still unclear, though, whether this relationship indicates causation. We conducted a Mendelian randomization investigation on two samples to fully uncover gut microbiota's potential genetic causal role in prostatitis. METHOD Prostatitis (1859 prostatitis cases and 72,799 controls) was utilized as the outcome, while SNPs highly linked with 196 microbial taxa (18 340 people) were chosen as instrumental factors. Random effects, inverse variance weighting, weighted medians, and MR-Egger were used to analyze causal effects. The Cochran's Q test, funnel plot, leave-one-out analysis, and MR-Egger intercept test were all used in the sensitivity analysis. RESULTS A causal effect in lowering the incidence of prostatitis is anticipated for five gut microorganisms (Methanobacteria, Methanobacteriaceae, Erysipelatoclostridium, Parasutterella, and Slackia; P < 0.05). Four gut bacteria, including Faecalibacterium, LachnospiraceaeUCG004, Sutterella, and Gastranaerophilales, are predicted to play a causal role in increasing the risk of prostatitis (P < 0.05). There were no discernible estimates of pleiotropy or heterogeneity. CONCLUSION Our investigation established the genetic links between nine gut microorganisms and prostatitis, which may offer fresh perspectives and a theoretical framework for the future prevention and management of prostatitis.
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Affiliation(s)
- Cheng Shen
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China
- Medical Research Center, Affiliated Hospital 2 of Nantong University, Nantong, China
| | - Zhan Chen
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China
- Medical Research Center, Affiliated Hospital 2 of Nantong University, Nantong, China
| | - Wei Zhang
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China
| | - Xinfeng Chen
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China
| | - Bing Zheng
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China.
| | - Chunmei Shi
- Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, China.
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Zhao D, Li G, Bai W, Teng J, Yan B, Han C. Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study. Front Immunol 2023; 14:1269069. [PMID: 38162659 PMCID: PMC10755900 DOI: 10.3389/fimmu.2023.1269069] [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: 07/29/2023] [Accepted: 11/30/2023] [Indexed: 01/03/2024] Open
Abstract
Background Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive. Methods We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness. Results A causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017-1.082, P=0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783-1.129, P=0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leave-one-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings. Conclusion This study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.
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Affiliation(s)
- Diqian Zhao
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Guobi Li
- Department of Pediatric Orthopedics, Affiliated Hospital of Shandong Traditional Chinese Medicine University, Jinan, China
| | - Wenzhe Bai
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jiawen Teng
- Department of Micro Orthopedics, Affiliated Hospital of Shandong Traditional Chinese Medicine University, Jinan, China
| | - Bing Yan
- Department of Joint Oncology Orthopedics, Affiliated Hospital of Shandong Traditional Chinese Medicine University, Jinan, China
| | - Cong Han
- Nephropathy Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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15
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Jiang L, Li JC, Tang BS, Guo JF. Associations between gut microbiota and Parkinson disease: A bidirectional Mendelian randomization analysis. Eur J Neurol 2023; 30:3471-3477. [PMID: 37159496 DOI: 10.1111/ene.15848] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/21/2023] [Accepted: 04/24/2023] [Indexed: 05/11/2023]
Abstract
BACKGROUND AND PURPOSE Parkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in humans. METHODS We performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases). RESULTS Twelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval [CI] = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition. CONCLUSIONS These results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.
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Affiliation(s)
- Li Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Jin-Chen Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Bioinformatics Center and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Bei-Sha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Bioinformatics Center and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Ji-Feng Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Bioinformatics Center and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Nitzan Z, Staun-Ram E, Volkowich A, Miller A. Multiple Sclerosis-Associated Gut Microbiome in the Israeli Diverse Populations: Associations with Ethnicity, Gender, Disability Status, Vitamin D Levels, and Mediterranean Diet. Int J Mol Sci 2023; 24:15024. [PMID: 37834472 PMCID: PMC10573818 DOI: 10.3390/ijms241915024] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/19/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Microbiome dysbiosis is increasingly being recognized as implicated in immune-mediated disorders including multiple sclerosis (MS). The microbiome is modulated by genetic and environmental factors including lifestyle, diet, and drug intake. This study aimed to characterize the MS-associated gut microbiome in the Israeli populations and to identify associations with demographic, dietary, and clinical features. The microbiota from 57 treatment-naive patients with MS (PwMS) and 43 age- and gender-matched healthy controls (HCs) was sequenced and abundance compared. Associations between differential microbes with demographic or clinical characteristics, as well as diet and nutrient intake, were assessed. While there was no difference in α- or β-diversity of the microbiome, we identified 40 microbes from different taxonomic levels that differ in abundance between PwMS and HCs, including Barnesiella, Collinsella, Egerthella, Mitsuokella, Olsenella Romboutsia, and Succinivibrio, all enhanced in PwMS, while several members of Lacnospira were reduced. Additional MS-differential microbes specific to ethnicity were identified. Several MS-specific microbial patterns were associated with gender, vitamin D level, Mediterranean diet, nutrient intake, or disability status. Thus, PwMS have altered microbiota composition, with distinctive patterns related to geographic locations and population. Microbiome dysbiosis seem to be implicated in disease progression, gender-related differences, and vitamin D-mediated immunological effects recognized in MS. Dietary interventions may be beneficial in restoring a "healthy microbiota" as part of applying comprehensive personalized therapeutic strategies for PwMS.
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Affiliation(s)
- Zehavit Nitzan
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel (E.S.-R.)
| | - Elsebeth Staun-Ram
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel (E.S.-R.)
- Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
| | - Anat Volkowich
- Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
| | - Ariel Miller
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel (E.S.-R.)
- Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
- Department of Neurology, Lady Davis Carmel Medical Center, Haifa 3436212, Israel
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Xu X, Xu Z, Yang B, Yi K, He F, Sun A, Li J, Luo Y, Wang J. Assessing the Effects of Dietary Cadmium Exposure on the Gastrointestinal Tract of Beef Cattle via Microbiota and Transcriptome Profile. Animals (Basel) 2023; 13:3104. [PMID: 37835710 PMCID: PMC10571678 DOI: 10.3390/ani13193104] [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: 09/16/2023] [Revised: 09/28/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
Cadmium (Cd) is an environmental pollutant, widely existing in soil, and can be absorbed and accumulated by plants. Hunan Province exhibits the worst cadmium contamination of farmland in China. Ruminants possess an abundant microbial population in the rumen, which enables them to tolerate various poisonous plants. To investigate whether the rumen microbiota could respond to Cd and mitigate the toxicity of Cd-accumulated maize to ruminants, 6-month-old cattle were fed with 85.82% (fresh basis) normal whole-plant maize silage diet (CON, n = 10) or Cd-accumulated whole-plant maize silage diet (CAM, n = 10) for 107 days. When compared to the CON cattle, CAM cattle showed significantly higher gain-to-feed ratio and an increased total bacterial population in the rumen, but a decreased total bacterial population in the colon. CAM cattle had higher relative abundance of Prevotella and Lachnospiraceae ND3007 group in the rumen, and Lachnospiraceae NK4A136 group and Clostridia vadinBB60 group in the colon. Notably, microbial correlations were enhanced in all segments of CAM cattle, especially Peptostreptococcaceae in the jejunum. Transcriptome analysis revealed down-regulation of several immune-related genes in the rumen of CAM cattle, and differentially expressed genes in the rumen were mostly involved in immune regulation. These findings indicated that feeding Cd-accumulated maize diet with a Cd concentration of 6.74 mg/kg dry matter (DM) could stimulate SCFA-related bacteria in the rumen, induce hormesis to promote weight gain, and improve energy utilization of cattle.
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Affiliation(s)
- Xinxin Xu
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (X.X.); (Z.X.); (B.Y.)
| | - Zebang Xu
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (X.X.); (Z.X.); (B.Y.)
| | - Bin Yang
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (X.X.); (Z.X.); (B.Y.)
- School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China
| | - Kangle Yi
- Hunan Institute of Animal and Veterinary Science, Changsha 410131, China; (K.Y.); (F.H.); (A.S.); (J.L.)
| | - Fang He
- Hunan Institute of Animal and Veterinary Science, Changsha 410131, China; (K.Y.); (F.H.); (A.S.); (J.L.)
| | - Ao Sun
- Hunan Institute of Animal and Veterinary Science, Changsha 410131, China; (K.Y.); (F.H.); (A.S.); (J.L.)
| | - Jianbo Li
- Hunan Institute of Animal and Veterinary Science, Changsha 410131, China; (K.Y.); (F.H.); (A.S.); (J.L.)
| | - Yang Luo
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (X.X.); (Z.X.); (B.Y.)
- Hunan Institute of Animal and Veterinary Science, Changsha 410131, China; (K.Y.); (F.H.); (A.S.); (J.L.)
| | - Jiakun Wang
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (X.X.); (Z.X.); (B.Y.)
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Zhang F, Xiong Y, Wu K, Wang L, Ji Y, Zhang B. Genetic Insights into Intestinal Microbiota and Risk of Infertility: A Mendelian Randomization Study. Microorganisms 2023; 11:2319. [PMID: 37764164 PMCID: PMC10538041 DOI: 10.3390/microorganisms11092319] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/05/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND The interaction between intestinal microbiota and infertility is less researched. This study was performed to investigate the causal association between gut microbiota and infertility. METHODS In this two-sample Mendelian randomization (MR) study, genetic variants of intestinal microbiota were obtained from the MiBioGen consortium, which included 18,340 individuals. Inverse variance weighting (IVW), MR-Egger, weighted median, maximum likelihood, MR Robust adjusted profile score, MR Pleiotropy residual sum, and outlier (MR-PRESSO) methods were used to explore the causal links between intestinal microbiota and infertility. The MR-Egger intercept term and the global test from the MR-PRESSO estimator were used to assess the horizontal pleiotropy. The Cochran Q test was applied to evaluate the heterogeneity of instrumental variables (IVs). RESULTS As indicated by the IVW estimator, significantly protective effects of the Family XIII AD3011 group (OR = 0.87) and Ruminococcaceae NK4A214 group (OR = 0.85) were identified for female fertility, while Betaproteobacteria (OR = 1.18), Burkholderiales (OR = 1.18), Candidatus Soleaferrea (OR = 1.12), and Lentisphaerae (OR = 1.11) showed adverse effects on female fertility. Meanwhile, Bacteroidaceae (OR = 0.57), Bacteroides (OR = 0.57), and Ruminococcaceae NK4A214 group (OR = 0.61) revealed protective effects on male fertility, and a causal association between Anaerotruncus (OR = 1.81) and male infertility was detected. The effect sizes and directions remained consistent in the other five methods except for Candidatus Soleaferrea. No heterogeneity or pleiotropy were identified by Cochran's Q test, MR-Egger, and global test (all p > 0.05). CONCLUSIONS This two-sample MR study revealed that genetically proxied intestinal microbiota had potentially causal effects on infertility. In all, the Ruminococcaceae NK4A214 group displayed protective effects against both male and female infertility. Further investigations are needed to establish the biological mechanisms linking gut microbiota and infertility.
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Affiliation(s)
- Fuxun Zhang
- Department of Urology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
| | - Yang Xiong
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kan Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Linmeng Wang
- Department of Urology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
| | - Yunhua Ji
- Department of Urology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
| | - Bo Zhang
- Department of Urology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
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Xue Y, Zhang L, Chen Y, Wang H, Xie J. Gut microbiota and atopic dermatitis: a two-sample Mendelian randomization study. Front Med (Lausanne) 2023; 10:1174331. [PMID: 37425302 PMCID: PMC10323683 DOI: 10.3389/fmed.2023.1174331] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Background Accumulating evidence suggests that alterations in gut microbiota composition and diversity are associated with Atopic dermatitis (AD). But until now, the causal association between them has been unclear. Methods We employed a two-sample Mendelian Randomization (MR) study to estimate the potential causality of gut microbiota on AD risk. The summary statistics related to the gut microbiota were obtained from a large-scale genome-wide genotype and 16S fecal microbiome dataset from 18,340 individuals (24 cohorts) analyzed by the MiBioGen Consortium, comprising 211 gut microbiota. AD data were also derived from strictly defined AD data collected by FinnGen biobank analysis, which included 218,467 European ancestors (5,321 AD patients and 213,146 controls). The inverse variance weighted method (IVW), weighted median (WME), and MR-Egger were used to determine the changes of AD pathogenic bacterial taxa, followed by sensitivity analysis including horizontal pleiotropy analysis, Cochran's Q test, and the leave-one-out method to assess the reliability of the results. In addition, MR Steiger's test was used to test the suppositional relationship between exposure and outcome. Results A total of 2,289 SNPs (p < 1 × 10-5) were included, including 5 taxa and 17 bacterial characteristics (1 phylum, 3 classes, 1 order, 4 families, and 8 genera), after excluding the IVs with linkage disequilibrium (LD). Combining the analysis of the results of the IVW models, there were 6 biological taxa (2 families, and 4 genera) of the intestinal flora positively associated with the risk of AD and 7 biological taxa (1 phylum, 2 classes, 1 order, 1 family, and 2 genera) of the intestinal flora negatively associated. The IVW analysis results showed that Tenericutes, Mollicutes, Clostridia, Bifidobacteriaceae, Bifidobacteriales, Bifidobacterium, and Christensenellaceae R 7 group were negatively correlated with the risk of AD, while Clostridiaceae 1, Bacteroidaceae, Bacteroides, Anaerotruncus, the unknown genus, and Lachnospiraceae UCG001 showed the opposite trend. And the results of the sensitivity analysis were robust. MR Steiger's test showed a potential causal relationship between the above intestinal flora and AD, but not vice versa. Conclusion The present MR analysis genetically suggests a causal relationship between changes in the abundance of the gut microbiota and AD risk, thus not only providing support for gut microecological therapy of AD but also laying the groundwork for further exploration of the mechanisms by which the gut microbiota contributes to the pathogenesis of AD.
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Affiliation(s)
- Yan Xue
- The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, Chengdu, China
| | - Linzhu Zhang
- The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, Chengdu, China
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yajun Chen
- The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, Chengdu, China
- North Sichuan Medical College, Nanchong, Sichuan, China
| | - Han Wang
- The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, Chengdu, China
| | - Jiang Xie
- The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, Chengdu, China
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Zhang J, Zhao Q, Qin Y, Si W, Zhang H, Zhang J. The Effect of Epimedium Isopentenyl Flavonoids on the Broiler Gut Health Using Microbiomic and Metabolomic Analyses. Int J Mol Sci 2023; 24:ijms24087646. [PMID: 37108810 PMCID: PMC10141048 DOI: 10.3390/ijms24087646] [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: 02/26/2023] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 04/29/2023] Open
Abstract
Epimedium (EM), also known as barrenwort, is a traditional medicinal plant rich in isopentenyl flavonols, which have beneficial biological activities and can improve human and animal health, but its mechanism is still unclear. In this study, ultra-high-performance liquid chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF/MS) and ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) were used to analyse the main components of EM, and isopentenyl flavonols such as Epimedin A, B, and C as well as Icariin were the major components of EM. Meanwhile, broilers were selected as model animals to illuminate the mechanism of Epimedium isopentenyl flavonols (EMIE) on gut health. The results showed that supplementation with 200 mg/kg EM improved the immune response, increased cecum short-chain fatty acids (SCFAs) and lactate concentrations, and improved nutrient digestibility in broilers. In addition, 16S rRNA sequencing showed that EMIE altered the composition of cecal microbiome, increasing the relative abundance of beneficial bacteria (Candidatus Soleaferrea and Lachbospiraceae NC2004 group and Butyricioccus) and reducing that of harmful bacteria (UBA1819, Negativibacillus, and Eisenbergiella). Metabolomic analysis identified 48 differential metabolites, of which Erosnin and Tyrosyl-Tryptophan were identified as core biomarkers. Erosnin and tyrosyl-tryptophan are potential biomarkers to evaluate the effects of EMIE. This shows that EMIE may regulate the cecum microbiota through Butyricicoccus, with changes in the relative abundance of the genera Eisenbergiella and Un. Peptostreptococcaceae affecting the serum metabolite levels of the host. EMIE is an excellent health product, and dietary isopentenyl flavonols, as bioactive components, can improve health by altering the microbiota structure and the plasma metabolite profiles. This study provides the scientific basis for the future application of EM in diets.
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Affiliation(s)
- Jiaqi Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Qingyu Zhao
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yuchang Qin
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Wei Si
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Huiyan Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Junmin Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China
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Ren Z, Xu Z, Amakye WK, Liu W, Zhao Z, Gao L, Wang M, Ren J. Hericium erinaceus mycelium-Derived Polysaccharide Alleviates Ulcerative Colitis and Modulates Gut Microbiota in Cynomolgus Monkeys. Mol Nutr Food Res 2023; 67:e2200450. [PMID: 36443636 DOI: 10.1002/mnfr.202200450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/25/2022] [Indexed: 11/30/2022]
Abstract
SCOPE Ulcerative colitis (UC) is rapidly increasing worldwide but prolong use of available corticosteroids treatment is associated with numerous adverse effects. There is the urgent need to develop novel therapeutic options. However, this requires the use of suitable disease models, but current models are generated with chemical agents mainly in rodents, which are unable to recapitulate the human occurrence. The aim of this study is to validate the occurrence of spontaneous UC in cynomolgus monkeys and explore the potential of Hericium erinaceus mycelium-derived polysaccharide in reversing UC pathologies. METHODS AND RESULTS Postmortem bowel evaluation and biochemical analysis including inflammatory markers and fecal occult blood testing (FOBT) as well as nutrition status parameters, confirm the non-artificial induced spontaneous occurrence of UC in cynomolgus monkeys. Subsequently, H. erinaceus mycelium-derived polysaccharide supplementation significantly attenuates UC pathologies, improves nutritional status, reduces the incidence of diarrhea, and reduces inflammation in UC monkeys. Importantly, the polysaccharides administration enhances intestinal function and reshapes the gut microbiota. CONCLUSION The study confirms the spontaneous UC monkeys can closely mimic the occurrence of UC in humans. Moreover, H. erinaceus mycelium-derived polysaccharide can effectively restore UC in monkeys, which show the prospects as precision nutritional supplement for the management of UC.
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Affiliation(s)
- Zhengyu Ren
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China.,State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, 999078, China
| | - Zhenzhen Xu
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China
| | - William Kwame Amakye
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China
| | - Wei Liu
- Guangzhou Huazhen Biosciences Co., Ltd., Guangzhou, Guangdong, 510900, China
| | - Zikuan Zhao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China
| | - Li Gao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China
| | - Min Wang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China
| | - Jiaoyan Ren
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510640, China.,China-Singapore International Joint Research Institute, Guangzhou, Guangdong, 510555, China
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22
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Qiao X, Zhang K, Li X, Lv Z, Wei W, Zhou R, Yan L, Pan Y, Yang S, Sun X, Li P, Xu C, Feng Y, Tian Z. Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis. Front Cell Infect Microbiol 2022; 12:1018897. [PMID: 36590590 PMCID: PMC9798431 DOI: 10.3389/fcimb.2022.1018897] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
Background Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis. Methods DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed. Results In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss. Conclusions The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.
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Affiliation(s)
- Xiaochen Qiao
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
- Department of Orthopedics, JinZhong Hospital Affiliated to Shanxi Medical University, Jinzhong, Shanxi, China
| | - Kun Zhang
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Xiaoyan Li
- Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhi Lv
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Wenhao Wei
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Ruhao Zhou
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Lei Yan
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Yongchun Pan
- Department of Orthopedics, Third People’s Hospital of Datong City, Datong, Shanxi, China
| | - Sen Yang
- Department of Orthopedics, The Second People’s Hospital of Changzhi, Changzhi, Shanxi, China
| | - Xiaojuan Sun
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Pengcui Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Chaojian Xu
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Yi Feng
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Zhi Tian
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
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Li ZJ, Gou HZ, Zhang YL, Song XJ, Zhang L. Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value. World J Gastroenterol 2022; 28:6213-6229. [PMID: 36504550 PMCID: PMC9730442 DOI: 10.3748/wjg.v28.i44.6213] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/31/2022] [Accepted: 11/10/2022] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.
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Affiliation(s)
- Zhen-Jiao Li
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hong-Zhong Gou
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yu-Lin Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Xiao-Jing Song
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Lei Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
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Hu Y, Jin X, Gao F, Lin T, Zhu H, Hou X, Yin Y, Kan S, Chen D. Selenium-enriched Bifidobacterium longum DD98 effectively ameliorates dextran sulfate sodium-induced ulcerative colitis in mice. Front Microbiol 2022; 13:955112. [PMID: 35992694 PMCID: PMC9389208 DOI: 10.3389/fmicb.2022.955112] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
The pathogenesis of ulcerative colitis (UC) is complicated with impaired intestinal epithelial barrier and imbalanced gut microbiota. Both selenium and probiotics have shown effects in regulating intestinal flora and ameliorating UC. The objective of this study is to investigate the alleviating effects of Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanism. After treatment of B. longum DD98, Se-B. longum DD98, and sulfasalazine for 3 weeks, the disease severity of UC mice was decreased, with colon lengthened and pathological phenotype improved. The expression of pro-inflammatory cytokines and oxidative stress parameters were also decreased. Thus, Se-B. longum DD98 showed a stronger effect on relieving the aforementioned symptoms caused by DSS-induced colitis. Exploration of the potential mechanism demonstrated that Se-B. longum DD98 showed higher activities to suppress the inflammatory response by inhibiting the activation of the toll-like receptor 4 (TLR4), compared to B. longum DD98 and sulfasalazine. Se-B. longum DD98 also significantly improved the intestinal barrier integrity by increasing the expression of tight junction proteins including ZO-1 and occludin. 16S rDNA sequencing analyses showed that Se-B. longum DD98 improved the diversity of the intestinal flora and promoted the abundance of health-benefiting taxa including Lachnospiraceae, Lactobacillaceae, and Prevotellaceae in family level. In conclusion, compared to B. longum DD98 and sulfasalazine, Se-B. longum DD98 showed stronger therapeutic effects on DSS-induced colitis in mice and might be a promising candidate for the treatment of UC.
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Affiliation(s)
- Yongjia Hu
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai, China
| | - Xueli Jin
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Fei Gao
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Ting Lin
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Zhu
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Hou
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Yin
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Shidong Kan
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Daijie Chen
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Daijie Chen,
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Milletich PL, Ahrens AP, Russell JT, Petrone JR, Berryman MA, Agardh D, Ludvigsson JF, Triplett EW, Ludvigsson J. Gut microbiome markers in subgroups of HLA class II genotyped infants signal future celiac disease in the general population: ABIS study. Front Cell Infect Microbiol 2022; 12:920735. [PMID: 35959362 PMCID: PMC9357981 DOI: 10.3389/fcimb.2022.920735] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 06/24/2022] [Indexed: 12/12/2022] Open
Abstract
Although gut microbiome dysbiosis has been illustrated in celiac disease (CD), there are disagreements about what constitutes these microbial signatures and the timeline by which they precede diagnosis is largely unknown. The study of high-genetic-risk patients or those already with CD limits our knowledge of dysbiosis that may occur early in life in a generalized population. To explore early gut microbial imbalances correlated with future celiac disease (fCD), we analyzed the stool of 1478 infants aged one year, 26 of whom later acquired CD, with a mean age of diagnosis of 10.96 ± 5.6 years. With a novel iterative control-matching algorithm using the prospective general population cohort, All Babies In Southeast Sweden, we found nine core microbes with prevalence differences and seven differentially abundant bacteria between fCD infants and controls. The differences were validated using 100 separate, iterative permutations of matched controls, which suggests the bacterial signatures are significant in fCD even when accounting for the inherent variability in a general population. This work is the first to our knowledge to demonstrate that gut microbial differences in prevalence and abundance exist in infants aged one year up to 19 years before a diagnosis of CD in a general population.
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Affiliation(s)
- Patricia L. Milletich
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
| | - Angelica P. Ahrens
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
| | - Jordan T. Russell
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
| | - Joseph R. Petrone
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
| | - Meghan A. Berryman
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
| | - Daniel Agardh
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| | - Eric W. Triplett
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States
- *Correspondence: Eric W. Triplett,
| | - Johnny Ludvigsson
- Crown Princess Victoria’s Children’s Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Sobh MM, Abdalbary M, Elnagar S, Nagy E, Elshabrawy N, Abdelsalam M, Asadipooya K, El-Husseini A. Secondary Osteoporosis and Metabolic Bone Diseases. J Clin Med 2022; 11:2382. [PMID: 35566509 PMCID: PMC9102221 DOI: 10.3390/jcm11092382] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/17/2022] [Accepted: 04/20/2022] [Indexed: 02/04/2023] Open
Abstract
Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis.
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Affiliation(s)
- Mahmoud M. Sobh
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Mohamed Abdalbary
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY 40506, USA
| | - Sherouk Elnagar
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Eman Nagy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Nehal Elshabrawy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Mostafa Abdelsalam
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Kamyar Asadipooya
- Division of Endocrinology, University of Kentucky, Lexington, KY 40506, USA;
| | - Amr El-Husseini
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY 40506, USA
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