Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

JIANG Shenghu ,  SHEN Bin

Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

SHEN Bin, Email: shenbin_1971@163.com

Keywords：

Osteoarthritis; gut microbiota dysbiosis; low-grade inflammation; metabolic syndrome

DOI：

10.7507/1002-1892.202212037

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To introduce the research progress on the relationship between gut microbiota dysbiosis and osteoarthritis (OA), focus on the possible mechanism of gut microbiota dysbiosis promoting OA, and propose a new therapeutic direction. Methods The domestic and foreign research literature on the relationship between gut microbiota dysbiosis and OA was reviewed. The role of the former in the occurrence and development of OA and the new ideas for the treatment of OA were summarized. Results The gut microbiota dysbiosis promotes the development of OA mainly in three aspects. First, the gut microbiota dysbiosis destroys intestinal permeability and causes low-grade inflammation, which aggravate OA. Secondly, the gut microbiota dysbiosis promotes the development of OA through metabolic syndrome. Thirdly, the gut microbiota dysbiosis is involved in the development of OA by regulating the metabolism and transport of trace elements. Studies have shown that improving gut microbiota dysbiosis by taking probiotics and transplanting fecal microbiota can reduce systemic inflammation and regulate metabolic balance, thus treating OA. Conclusion Gut microbiota dysbiosis is closely related to the development of OA, and improving gut microbiota dysbiosis can be an important idea for OA treatment.

Citation： JIANG Shenghu, SHEN Bin. Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(3): 371-376. doi: 10.7507/1002-1892.202212037 Copy

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2.	Millerand M, Berenbaum F, Jacques C. Danger signals and inflammaging in osteoarthritis. Clin Exp Rheumatol, 2019, 37 Suppl 120(5): 48-56.
3.	Wei Z, Li F, Pi G. Association between gut microbiota and osteoarthritis: A review of evidence for potential mechanisms and therapeutics. Front Cell Infect Microbiol, 2022, 12: 812596. doi: 10.3389/fcimb.2022.812596.
4.	Chen Y, Zhou J, Wang L. Role and mechanism of gut microbiota in human disease. Front Cell Infect Microbiol, 2021, 11: 625913. doi: 10.3389/fcimb.2021.625913.
5.	Malesza IJ, Malesza M, Walkowiak J, et al. High-Fat, western-style diet, systemic inflammation, and gut microbiota: A narrativereview. Cells, 2021, 10(11): 3164. doi: 10.3390/cells10113164.
6.	Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res, 2020, 30(6): 492-506.
7.	Thomas MS, Blesso CN, Calle MC, et al. Dietary influences on gut microbiota with a focus on metabolic syndrome. Metab Syndr Relat Disord, 2022, 20(8): 429-439.
8.	Xie Y, Zhou W, Zhong Z, et al. Metabolic syndrome, hypertension, and hyperglycemia were positively associated with knee osteoarthritis, while dyslipidemia showed no association with knee osteoarthritis. Clin Rheumatol, 2021, 40(2): 711-724.
9.	Ghosh SS, Wang J, Yannie PJ, et al. Intestinal barrier dysfunction, LPS translocation, and disease development. J Endocr Soc, 2020, 4(2): bvz039. doi: 10.1210/jendso/bvz039.
10.	Li M, Ding J, Stanton C, et al. Bifidobacterium longum subsp. infantis FJSYZ1M3 ameliorates DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying gut microbiota. Food Funct, 2023, 14(1): 354-368.
11.	Hodgkinson K, El Abbar F, Dobranowski P, et al. Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr, 2022, 42(2): 61-75.
12.	Seethaler B, Nguyen NK, Basrai M, et al. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am J Clin Nutr, 2022, 116(4): 928-942.
13.	Boer CG, Radjabzadeh D, Medina-Gomez C, et al. Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun, 2019, 10(1): 4881. doi: 10.1038/s41467-019-12873-4.
14.	Wei J, Zhang C, Zhang Y, et al. Association between gut microbiota and symptomatic hand osteoarthritis: Data from the Xiangya Osteoarthritis Study. Arthritis Rheumatol, 2021, 73(9): 1656-1662.
15.	Huang ZY, Stabler T, Pei FX, et al. Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis Cartilage, 2016, 24(10): 1769-1775.
16.	Collins KH, Paul HA, Reimer RA, et al. Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model. Osteoarthritis Cartilage, 2015, 23(11): 1989-1998.
17.	Hernandez CJ. The microbiome and bone and joint disease. Curr Rheumatol Rep, 2017, 19(12): 77. doi: 10.1007/s11926-017-0705-1.
18.	Guido G, Ausenda G, Iascone V, et al. Gut permeability and osteoarthritis, towards a mechanistic understanding of the pathogenesis: a systematic review. Ann Med, 2021, 53(1): 2380-2390.
19.	Won Y, Yang JI, Park S, et al. Lipopolysaccharide binding protein and CD14, cofactors of Toll-like receptors, are essential for low-grade inflammation-induced exacerbation of cartilage damage in mouse models of posttraumatic osteoarthritis. Arthritis Rheumatol, 2021, 73(8): 1451-1460.
20.	Lu J, Zhang H, Pan J, et al. Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways. Arthritis Res Ther, 2021, 23(1): 142. doi: 10.1186/s13075-021-02512-z.
21.	Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage, 2020, 28(5): 555-561.
22.	Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 2021, 19(1): 55-71.
23.	Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier. Gut, 2016, 65(2): 330-339.
24.	Liu SY, Zhu WT, Chen BW, et al. Bidirectional association between metabolic syndrome and osteoarthritis: a meta-analysis of observational studies. Diabetol Metab Syndr, 2020, 12: 38. doi: 10.1186/s13098-020-00547-x.
25.	Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic syndrome: Updates on pathophysiology and management in 2021. Int J Mol Sci, 2022, 23(2): 786. doi: 10.3390/ijms23020786.
26.	Croci S, D’Apolito LI, Gasperi V, et al. Dietary strategies for management of metabolic syndrome: Role of gut microbiota metabolites. Nutrients, 2021, 13(5): 1389. doi: 10.3390/nu13051389.
27.	Wang PX, Deng XR, Zhang CH, et al. Gut microbiota and metabolic syndrome. Chin Med J (Engl), 2020, 133(7): 808-816.
28.	Lemieux I, Després JP. Metabolic syndrome: Past, present and future. Nutrients, 2020, 12(11): 3501. doi: 10.3390/nu12113501.
29.	Xie C, Chen Q. Adipokines: new therapeutic target for osteoarthritis? Curr Rheumatol Rep, 2019, 21(12): 71. doi: 10.1007/s11926-019-0868-z.
30.	Feng X, Xiao J, Bai L. Role of adiponectin in osteoarthritis. Front Cell Dev Biol, 2022, 10: 992764. doi: 10.3389/fcell.2022.992764.
31.	Ait Eldjoudi D, Cordero Barreal A, Gonzalez-Rodríguez M, et al. Leptin in osteoarthritis and rheumatoid arthritis: Player or bystander? Int J Mol Sci, 2022, 23(5): 2859. doi: 10.3390/ijms23052859.
32.	Żaneta C, Danuta KB, Natalia ŁA, et al. Concentration of selected elements in the infrapatellar fat pad of patients with a history of total knee arthroplasty. Int J Environ Res Public Health, 2019, 16(10): 1734. doi: 10.3390/ijerph16101734.
33.	Nugzar O, Zandman-Goddard G, Oz H, et al. The role of ferritin and adiponectin as predictors of cartilage damage assessed by arthroscopy in patients with symptomatic knee osteoarthritis. Best Pract Res Clin Rheumatol, 2018, 32(5): 662-668.
34.	Sun K, Guo Z, Hou L, et al. Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential. Ageing Res Rev, 2021, 72: 101481. doi: 10.1016/j.arr.2021.101481.
35.	Yao X, Sun K, Yu S, et al. Chondrocyte ferroptosis contribute to the progression of osteoarthritis. J Orthop Translat, 2020, 27: 33-43.
36.	Kot K, Kosik-Bogacka D, Ziętek P, et al. Impact of varied factors on iron, nickel, molybdenum and vanadium concentrations in the knee joint. Int J Environ Res Public Health, 2020, 17(3): 813. doi: 10.3390/ijerph17030813.
37.	Zhou J, Liu C, Sun Y, et al. Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis. Osteoarthritis Cartilage, 2021, 29(7): 1029-1035.
38.	Frangos T, Maret W. Zinc and cadmium in the aetiology and pathogenesis of osteoarthritis and rheumatoid arthritis. Nutrients, 2020, 13(1): 53. doi: 10.3390/nu13010053.
39.	Li G, Cheng T, Yu X. The impact of trace elements on osteoarthritis. Front Med (Lausanne), 2021, 8: 771297.doi: 10.3389/fmed.2021.771297.
40.	Qi T, Weng J, Yu F, et al. Insights into the role of magnesium ions in affecting osteogenic differentiation of mesenchymal stem cells. Biol Trace Elem Res, 2021, 199(2): 559-567.
41.	Kuang X, Chiou J, Lo K, et al. Magnesium in joint health and osteoarthritis. Nutr Res, 2021, 90: 24-35.
42.	Shmagel A, Onizuka N, Langsetmo L, et al. Low magnesium intake is associated with increased knee pain in subjects with radiographic knee osteoarthritis: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage, 2018, 26(5): 651-658.
43.	Bielik V, Kolisek M. Bioaccessibility and bioavailability of minerals in relation to a healthy gut microbiome. Int J Mol Sci, 2021, 22(13): 6803. doi: 10.3390/ijms22136803.
44.	Cai X, Chen X, Yin N, et al. Estimation of the bioaccessibility and bioavailability of Fe, Mn, Cu, and Zn in Chinese vegetables using the in vitro digestion/Caco-2 cell model: the influence of gut microbiota. Food Funct, 2017, 8(12): 4592-4600.
45.	Celis AI, Relman DA. Competitors versus collaborators: Micronutrient processing by pathogenic and commensal human-associated gut bacteria. Mol Cell, 2020, 78(4): 570-576.
46.	Jang S, Lee K, Ju JH. Recent updates of diagnosis, pathophysiology, and treatment on osteoarthritis of the knee. Int J Mol Sci, 2021, 22(5): 2619. doi: 10.3390/ijms22052619.
47.	Cho Y, Jeong S, Kim H, et al. Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions. Exp Mol Med, 2021, 53(11): 1689-1696.
48.	Ghouri A, Conaghan PG. Update on novel pharmacological therapies for osteoarthritis. Ther Adv Musculoskelet Dis, 2019, 11: 1759720X19864492. doi: 10.1177/1759720X19864492. eCollection 2019.
49.	Jhun J, Cho KH, Lee DH, et al. Oral administration of lactobacillus rhamnosus ameliorates the progression of osteoarthritis by inhibiting joint pain and inflammation. Cells, 2021, 10(5): 1057. doi: 10.3390/cells10051057.
50.	Arora V, Singh G, O-Sullivan I, et al. Gut-microbiota modulation: The impact of thegut-microbiotaon osteoarthritis. Gene, 2021, 785: 145619. doi: 10.1016/j.gene.2021.145619.
51.	Kalinkovich A, Livshits G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies. Semin Arthritis Rheum, 2019, 49(3): 474-484.
52.	Lee SH, Kwon JY, Jhun J, et al. Lactobacillus acidophilus ameliorates pain and cartilage degradation in experimental osteoarthritis. Immunol Lett, 2018, 203: 6-14.
53.	Lei M, Guo C, Wang D, et al. The effect of probiotic lactobacillus casei shirota on knee osteoarthritis: a randomised double-blind, placebo-controlled clinical trial. Benef Microbes, 2017, 8(5): 697-703.
54.	Li K, Liu A, Zong W, et al. Moderate exercise ameliorates osteoarthritis by reducing lipopolysaccharides from gut microbiota in mice. Saudi J Biol Sci, 2021, 28(1): 40-49.
55.	Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr, 2011, 94(1): 58-65.
56.	Antushevich H. Fecal microbiota transplantation in disease therapy. Clin Chim Acta, 2020, 503: 90-98.
57.	Huang Z, Chen J, Li B, et al. Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice. Ann Rheum Dis, 2020, 79(5): 646-656.
58.	Khoruts A, Staley C, Sadowsky MJ. Faecal microbiota transplantation for clostridioides difficile: mechanisms and pharmacology. Nat Rev Gastroenterol Hepatol, 2021, 18(1): 67-80.
59.	de Groot P, Scheithauer T, Bakker GJ, et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut, 2020, 69(3): 502-512.

1. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019, 393(10182): 1745-1759.
2. Millerand M, Berenbaum F, Jacques C. Danger signals and inflammaging in osteoarthritis. Clin Exp Rheumatol, 2019, 37 Suppl 120(5): 48-56.
3. Wei Z, Li F, Pi G. Association between gut microbiota and osteoarthritis: A review of evidence for potential mechanisms and therapeutics. Front Cell Infect Microbiol, 2022, 12: 812596. doi: 10.3389/fcimb.2022.812596.
4. Chen Y, Zhou J, Wang L. Role and mechanism of gut microbiota in human disease. Front Cell Infect Microbiol, 2021, 11: 625913. doi: 10.3389/fcimb.2021.625913.
5. Malesza IJ, Malesza M, Walkowiak J, et al. High-Fat, western-style diet, systemic inflammation, and gut microbiota: A narrativereview. Cells, 2021, 10(11): 3164. doi: 10.3390/cells10113164.
6. Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res, 2020, 30(6): 492-506.
7. Thomas MS, Blesso CN, Calle MC, et al. Dietary influences on gut microbiota with a focus on metabolic syndrome. Metab Syndr Relat Disord, 2022, 20(8): 429-439.
8. Xie Y, Zhou W, Zhong Z, et al. Metabolic syndrome, hypertension, and hyperglycemia were positively associated with knee osteoarthritis, while dyslipidemia showed no association with knee osteoarthritis. Clin Rheumatol, 2021, 40(2): 711-724.
9. Ghosh SS, Wang J, Yannie PJ, et al. Intestinal barrier dysfunction, LPS translocation, and disease development. J Endocr Soc, 2020, 4(2): bvz039. doi: 10.1210/jendso/bvz039.
10. Li M, Ding J, Stanton C, et al. Bifidobacterium longum subsp. infantis FJSYZ1M3 ameliorates DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying gut microbiota. Food Funct, 2023, 14(1): 354-368.
11. Hodgkinson K, El Abbar F, Dobranowski P, et al. Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr, 2022, 42(2): 61-75.
12. Seethaler B, Nguyen NK, Basrai M, et al. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am J Clin Nutr, 2022, 116(4): 928-942.
13. Boer CG, Radjabzadeh D, Medina-Gomez C, et al. Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun, 2019, 10(1): 4881. doi: 10.1038/s41467-019-12873-4.
14. Wei J, Zhang C, Zhang Y, et al. Association between gut microbiota and symptomatic hand osteoarthritis: Data from the Xiangya Osteoarthritis Study. Arthritis Rheumatol, 2021, 73(9): 1656-1662.
15. Huang ZY, Stabler T, Pei FX, et al. Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis Cartilage, 2016, 24(10): 1769-1775.
16. Collins KH, Paul HA, Reimer RA, et al. Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model. Osteoarthritis Cartilage, 2015, 23(11): 1989-1998.
17. Hernandez CJ. The microbiome and bone and joint disease. Curr Rheumatol Rep, 2017, 19(12): 77. doi: 10.1007/s11926-017-0705-1.
18. Guido G, Ausenda G, Iascone V, et al. Gut permeability and osteoarthritis, towards a mechanistic understanding of the pathogenesis: a systematic review. Ann Med, 2021, 53(1): 2380-2390.
19. Won Y, Yang JI, Park S, et al. Lipopolysaccharide binding protein and CD14, cofactors of Toll-like receptors, are essential for low-grade inflammation-induced exacerbation of cartilage damage in mouse models of posttraumatic osteoarthritis. Arthritis Rheumatol, 2021, 73(8): 1451-1460.
20. Lu J, Zhang H, Pan J, et al. Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways. Arthritis Res Ther, 2021, 23(1): 142. doi: 10.1186/s13075-021-02512-z.
21. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage, 2020, 28(5): 555-561.
22. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 2021, 19(1): 55-71.
23. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier. Gut, 2016, 65(2): 330-339.
24. Liu SY, Zhu WT, Chen BW, et al. Bidirectional association between metabolic syndrome and osteoarthritis: a meta-analysis of observational studies. Diabetol Metab Syndr, 2020, 12: 38. doi: 10.1186/s13098-020-00547-x.
25. Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic syndrome: Updates on pathophysiology and management in 2021. Int J Mol Sci, 2022, 23(2): 786. doi: 10.3390/ijms23020786.
26. Croci S, D’Apolito LI, Gasperi V, et al. Dietary strategies for management of metabolic syndrome: Role of gut microbiota metabolites. Nutrients, 2021, 13(5): 1389. doi: 10.3390/nu13051389.
27. Wang PX, Deng XR, Zhang CH, et al. Gut microbiota and metabolic syndrome. Chin Med J (Engl), 2020, 133(7): 808-816.
28. Lemieux I, Després JP. Metabolic syndrome: Past, present and future. Nutrients, 2020, 12(11): 3501. doi: 10.3390/nu12113501.
29. Xie C, Chen Q. Adipokines: new therapeutic target for osteoarthritis? Curr Rheumatol Rep, 2019, 21(12): 71. doi: 10.1007/s11926-019-0868-z.
30. Feng X, Xiao J, Bai L. Role of adiponectin in osteoarthritis. Front Cell Dev Biol, 2022, 10: 992764. doi: 10.3389/fcell.2022.992764.
31. Ait Eldjoudi D, Cordero Barreal A, Gonzalez-Rodríguez M, et al. Leptin in osteoarthritis and rheumatoid arthritis: Player or bystander? Int J Mol Sci, 2022, 23(5): 2859. doi: 10.3390/ijms23052859.
32. Żaneta C, Danuta KB, Natalia ŁA, et al. Concentration of selected elements in the infrapatellar fat pad of patients with a history of total knee arthroplasty. Int J Environ Res Public Health, 2019, 16(10): 1734. doi: 10.3390/ijerph16101734.
33. Nugzar O, Zandman-Goddard G, Oz H, et al. The role of ferritin and adiponectin as predictors of cartilage damage assessed by arthroscopy in patients with symptomatic knee osteoarthritis. Best Pract Res Clin Rheumatol, 2018, 32(5): 662-668.
34. Sun K, Guo Z, Hou L, et al. Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential. Ageing Res Rev, 2021, 72: 101481. doi: 10.1016/j.arr.2021.101481.
35. Yao X, Sun K, Yu S, et al. Chondrocyte ferroptosis contribute to the progression of osteoarthritis. J Orthop Translat, 2020, 27: 33-43.
36. Kot K, Kosik-Bogacka D, Ziętek P, et al. Impact of varied factors on iron, nickel, molybdenum and vanadium concentrations in the knee joint. Int J Environ Res Public Health, 2020, 17(3): 813. doi: 10.3390/ijerph17030813.
37. Zhou J, Liu C, Sun Y, et al. Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis. Osteoarthritis Cartilage, 2021, 29(7): 1029-1035.
38. Frangos T, Maret W. Zinc and cadmium in the aetiology and pathogenesis of osteoarthritis and rheumatoid arthritis. Nutrients, 2020, 13(1): 53. doi: 10.3390/nu13010053.
39. Li G, Cheng T, Yu X. The impact of trace elements on osteoarthritis. Front Med (Lausanne), 2021, 8: 771297.doi: 10.3389/fmed.2021.771297.
40. Qi T, Weng J, Yu F, et al. Insights into the role of magnesium ions in affecting osteogenic differentiation of mesenchymal stem cells. Biol Trace Elem Res, 2021, 199(2): 559-567.
41. Kuang X, Chiou J, Lo K, et al. Magnesium in joint health and osteoarthritis. Nutr Res, 2021, 90: 24-35.
42. Shmagel A, Onizuka N, Langsetmo L, et al. Low magnesium intake is associated with increased knee pain in subjects with radiographic knee osteoarthritis: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage, 2018, 26(5): 651-658.
43. Bielik V, Kolisek M. Bioaccessibility and bioavailability of minerals in relation to a healthy gut microbiome. Int J Mol Sci, 2021, 22(13): 6803. doi: 10.3390/ijms22136803.
44. Cai X, Chen X, Yin N, et al. Estimation of the bioaccessibility and bioavailability of Fe, Mn, Cu, and Zn in Chinese vegetables using the in vitro digestion/Caco-2 cell model: the influence of gut microbiota. Food Funct, 2017, 8(12): 4592-4600.
45. Celis AI, Relman DA. Competitors versus collaborators: Micronutrient processing by pathogenic and commensal human-associated gut bacteria. Mol Cell, 2020, 78(4): 570-576.
46. Jang S, Lee K, Ju JH. Recent updates of diagnosis, pathophysiology, and treatment on osteoarthritis of the knee. Int J Mol Sci, 2021, 22(5): 2619. doi: 10.3390/ijms22052619.
47. Cho Y, Jeong S, Kim H, et al. Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions. Exp Mol Med, 2021, 53(11): 1689-1696.
48. Ghouri A, Conaghan PG. Update on novel pharmacological therapies for osteoarthritis. Ther Adv Musculoskelet Dis, 2019, 11: 1759720X19864492. doi: 10.1177/1759720X19864492. eCollection 2019.
49. Jhun J, Cho KH, Lee DH, et al. Oral administration of lactobacillus rhamnosus ameliorates the progression of osteoarthritis by inhibiting joint pain and inflammation. Cells, 2021, 10(5): 1057. doi: 10.3390/cells10051057.
50. Arora V, Singh G, O-Sullivan I, et al. Gut-microbiota modulation: The impact of thegut-microbiotaon osteoarthritis. Gene, 2021, 785: 145619. doi: 10.1016/j.gene.2021.145619.
51. Kalinkovich A, Livshits G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies. Semin Arthritis Rheum, 2019, 49(3): 474-484.
52. Lee SH, Kwon JY, Jhun J, et al. Lactobacillus acidophilus ameliorates pain and cartilage degradation in experimental osteoarthritis. Immunol Lett, 2018, 203: 6-14.
53. Lei M, Guo C, Wang D, et al. The effect of probiotic lactobacillus casei shirota on knee osteoarthritis: a randomised double-blind, placebo-controlled clinical trial. Benef Microbes, 2017, 8(5): 697-703.
54. Li K, Liu A, Zong W, et al. Moderate exercise ameliorates osteoarthritis by reducing lipopolysaccharides from gut microbiota in mice. Saudi J Biol Sci, 2021, 28(1): 40-49.
55. Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr, 2011, 94(1): 58-65.
56. Antushevich H. Fecal microbiota transplantation in disease therapy. Clin Chim Acta, 2020, 503: 90-98.
57. Huang Z, Chen J, Li B, et al. Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice. Ann Rheum Dis, 2020, 79(5): 646-656.
58. Khoruts A, Staley C, Sadowsky MJ. Faecal microbiota transplantation for clostridioides difficile: mechanisms and pharmacology. Nat Rev Gastroenterol Hepatol, 2021, 18(1): 67-80.
59. de Groot P, Scheithauer T, Bakker GJ, et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut, 2020, 69(3): 502-512.

Chinese Journal of Reparative and Reconstructive Surgery

Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis

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