Differential analysis of gut microbiome in patients with periprosthetic joint infection, aseptic failure, and osteoarthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

Muzhabaier·Kari , LI Yicheng , WANG Fei , GUO Xiaobin , CHEN Quan , ZHANG Xiaogang ,  CAO Li

Department of Orthopedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi Xinjiang, 830054, P. R. China;

Corresponding?author：

CAO Li, Email: xjbone@sina.com

Keywords：

Periprosthetic joint infection; aseptic failure; osteoarthritis; gut microbiota dysbiosis; metagenomics next-generation sequencing

DOI：

10.7507/1002-1892.202601002

Video：

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Objective To explore the differences in gut microbiota diversity and structural characteristics among patients with periprosthetic joint infection (PJI), aseptic failure (AF), and osteoarthritis (OA), and to analyze the association between gut microbiota dysbiosis and the occurrence of PJI, thereby providing a new theoretical basis for elucidating the pathogenesis and treatment strategies of PJI in clinical practice. Methods The study enrolled patients with PJI and AF admitted between February 2024 and December 2024, as well as OA patients admitted in February 2024. A total of 52 PJI patients, 19 AF patients, and 29 OA patients who met the selection criteria were included in the analysis. Significant differences were observed among the three groups in terms of gender, age, surgical site, preoperative C-reactive protein levels, and erythrocyte sedimentation rate (P<0.05), while no significant difference was found in American Society of Anesthesiologists (ASA) classification and body mass index (P>0.05). Among the PJI patients, infection staging was as follows: 9 cases in the acute phase, 28 cases in the delayed phase, and 15 cases in the chronic phase; 23 cases were accompanied by sinus tract formation. Fecal samples were collected at different time points: for the PJI group, samples were obtained preoperatively and on postoperative days (7±1) and (14±1); for the AF group, preoperatively and on postoperative day (7±1); and for the OA group, preoperatively only. Metagenomics next-generation sequencing were employed to analyze gut microbiota α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) and differential bacterial genera (screened using the LEfSe algorithm). Results Analysis of gut microbiota diversity showed that the preoperative α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) in the PJI group were significantly lower than those in AF group and OA group (P<0.05). Compared with the AF group on postoperative day (7±1), the α-diversity indices in the PJI group on postoperative day (7±1) were lower, but the difference was not significant (P>0.05); by postoperative day (14±1), these indices further decreased, and the difference was significant (P<0.05). In the PJI group, no significant difference was observed in any of the indices across different time points postoperatively (P>0.05). Analysis of gut microbiota structural characteristics revealed that the PJI group exhibited characteristic dysbiosis both before and after operation. Preoperatively, the PJI group was characterized by enrichment of Pseudomonadota (relative abundance 13.19%), Enterobacteriaceae (Escherichia 3.26%, Klebsiella 1.90%), and opportunistic pathogens such as Enterococcus faecium (0.43%), while the relative abundances of Firmicutes (51.83%) and Bifidobacterium (0.24%) decreased. Postoperatively, the α-diversity in the PJI group further declined, with increased relative abundances of Escherichia and Klebsiella, and the relative abundance of Firmicutes decreased to 40.24%. LEfSe analysis of preoperative gut microbiota composition between the PJI group and AF group indicated that the AF group was predominated by Firmicutes, Bifidobacterium, and Roseburia preoperatively, with greater postoperative microbial stability compared to the PJI group. Conclusion Patients with PJI exhibited a gut microbiota profile characterized by reduced diversity and enrichment of opportunistic pathogens. Postoperative antibiotic treatment further aggravated this dysbiosis, providing new clinical insights into the role of gut microbiota imbalance in the pathogenesis and progression of PJI.

Citation： Muzhabaier·Kari, LI Yicheng, WANG Fei, GUO Xiaobin, CHEN Quan, ZHANG Xiaogang, CAO Li. Differential analysis of gut microbiome in patients with periprosthetic joint infection, aseptic failure, and osteoarthritis. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(4): 548-556. doi: 10.7507/1002-1892.202601002 Copy

1.	Patel R. Periprosthetic joint infection. N Engl J Med, 2023, 388(3): 251-262.
2.	Nelson SB, Pinkney JA, Chen AF, et al. Periprosthetic joint infection: current clinical challenges. Clin Infect Dis, 2023, 77(7): e34-e45.
3.	張克石, 吳婕, 徐超, 等. 人工關節假體周圍感染的診斷標準沿革與技術進展. 中華骨與關節外科雜志, 2024, 17(11): 1007-1014.
4.	國家骨科醫學中心保膝聯盟, 中華醫學會骨科學分會保膝學組, 中國老年保健協會骨關節保護與健康分會, 等. 單髁置換術后假體周圍感染預防中國專家共識. 實用骨科雜志, 2025, 31(1): 1-14.
5.	Kong L, Cao J, Zhang Y, et al. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. Int Wound J, 2017, 14(3): 529-536.
6.	Li J, Liu Z, Wang Z, et al. Risk factors for periprosthetic joint infection following primary total knee arthroplasty: a systematic review and meta-analysis. Front Surg, 2026, 12: 1715571. doi: 10.3389/fsurg.2025.1715571.
7.	Resende VAC, Neto AC, Nunes C, et al. Higher age, female gender, osteoarthritis and blood transfusion protect against periprosthetic joint infection in total hip or knee arthroplasties: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc, 2021, 29(1): 8-43.
8.	Ren X, Ling L, Qi L, et al. Patients’ risk factors for periprosthetic joint infection in primary total hip arthroplasty: a meta-analysis of 40 studies. BMC Musculoskelet Disord, 2021, 22(1): 776. doi: 10.1186/s12891-021-04647-1.
9.	Caballero-Flores G, Pickard JM, Nú?ez G. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat Rev Microbiol, 2023, 21(6): 347-360.
10.	Liang L, Yang Z, Fu X. Ecology of the gut microbiota and colonization resistance: mechanisms and therapeutic implications. FEMS Microbiol Ecol, 2025, 102(1): fiaf124. doi: 10.1093/femsec/fiaf124.
11.	Remily EA, Sax OC, Douglas SJ, et al. Inflammatory bowel disease is associated with increased complications after total knee arthroplasty. Knee, 2023, 40: 313-318.
12.	Chisari E, D’Mello D, Sherman MB, Parvizi J. Inflammatory bowel diseases increase the risk of periprosthetic joint infection. J Bone Joint Surg (Am), 2022, 104(2): 160-165.
13.	Krezalek MA, Hyoju S, Zaborin A, et al. Can methicillin-resistant Staphylococcus aureus silently travel from the gut to the wound and cause postoperative infection? Modeling the “Trojan horse” hypothesis. Ann Surg, 2018, 267(4): 749-758.
14.	Hernandez CJ, Yang X, Ji G, et al. Disruption of the gut microbiome increases the risk of periprosthetic joint infection in mice. Clin Orthop Relat Res, 2019, 477(11): 2588-2598.
15.	Levast B, Benech N, Gasc C, et al. Impact on the gut microbiota of intensive and prolonged antimicrobial therapy in patients with bone and joint infection. Front Med (Lausanne), 2021, 8: 586875. doi: 10.3389/fmed.2021.586875.
16.	Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic hip and knee infection: An evidence-based and validated criteria. J Arthroplasty, 2018, 33(5): 1309-1314.
17.	Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum, 1991, 34(5): 505-514.
18.	Ji B, Aimaiti A, Wang F, et al. Intraoperative direct sonication of implants and soft tissue for the diagnosis of periprosthetic joint infection. J Bone Joint Surg (Am), 2023, 105(11): 855-864.
19.	Li Y, Wang F, Wahafu T, et al. Intraoperative direct sonication versus conventional sonication in the diagnosis of periprosthetic joint infection: comparison of diagnostic accuracy and time to positivity of fluid culture. J Bone Joint Surg (Am), 2025, 107(13): 1439-1449.
20.	紀保超, 阿不都賽米·艾買提, 汪斐, 等. 非接觸式低頻超聲清創技術治療假體周圍感染早期效果的前瞻性單臂臨床研究. 中華外科雜志, 2023, 61(2): 129-137.
21.	謝政. 骨性關節炎患者腸道菌群結構特征及功能分析. 鄭州: 鄭州大學, 2020.
22.	Longo UG, Lalli A, Bandini B, et al. The influence of gut microbiome on periprosthetic joint infections: state-of-the-art. J ISAKOS, 2024, 9(3): 353-361.
23.	Ramasamy BR, Sharma DK, Callary SA, et al. Role of gut microbiota disruption in prosthetic joint infection: a scoping review. Lancet Microbe, 2025, 6(11): 101193. doi: 10.1016/j.lanmic.2025.101193.
24.	Singlitico A, Grassa D, Kaplan R, et al. The hidden connection between gut microbiota and periprosthetic joint infections: a scoping review. J Bone Joint Infect, 2025, 10(2): 85-92.
25.	Chisari E, Cho J, Wouthuyzen-Bakker M, et al. Gut permeability may be associated with periprosthetic joint infection after total hip and knee arthroplasty. Sci Rep, 2022, 12(1): 15094. doi: 10.1038/s41598-022-19034-6.
26.	中國食品科學技術學會益生菌分會. 人體腸道菌群主要特征的專家共識. 中國食品學報, 2024, 24(7): 460-470.
27.	Zheng Y, Zhang Z, Tang P, et al. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front Immunol, 2023, 14: 1143548. doi: 10.3389/fimmu.2023.1143548.
28.	Schlechte J, Zucoloto AZ, Yu IL, et al. Dysbiosis of a microbiota-immune metasystem in critical illness is associated with nosocomial infections. Nat Med, 2023, 29(4): 1017-1027.
29.	Ducarmon QR, Zwittink RD, Hornung BVH, et al. Gut microbiota and colonization resistance against bacterial enteric infection. Microbiol Mol Biol Rev, 2019, 83(3): e00007-19.
30.	劉有才, 李筱蟠, 魏春根, 等. 腸道菌群失調對反復呼吸道感染患兒免疫功能的影響. 吉林醫學, 2022, 43(4): 938-939.
31.	Fernandez Sanchez J, Maknojia AA, King KY. Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease. Blood, 2024, 143(17): 1689-1701.
32.	Zhang D, Chen G, Manwani D, et al. Neutrophil ageing is regulated by the microbiome. Nature, 2015, 525(7570): 528-532.
33.	Deshmukh HS, Liu Y, Menkiti OR, et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med, 2014, 20(5): 524-530.
34.	Wells C, Robertson T, Sheth P, et al. How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation. Heliyon, 2024, 10(12): e32831. doi: 10.1016/j.heliyon.2024.e32831.
35.	Khosravi A, Yá?ez A, Price JG, et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe, 2014, 15(3): 374-381.
36.	Rashid MU, Zaura E, Buijs MJ, et al. Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota. Clin Infect Dis, 2015, 60(Suppl 2): S77-S84.
37.	Stecher B, Maier L, Hardt WD. ‘Blooming’ in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol, 2013, 11(4): 277-284.
38.	Wei Y, Palacios Araya D, Palmer KL. Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics. Nat Rev Microbiol, 2024, 22(11): 705-721.
39.	Heckmann ND, Culler MW, Mont MA, et al. Emerging concepts in periprosthetic joint infection research: the human microbiome. J Arthroplasty, 2025, 40(7): 1821-1826.
40.	劉夢, 張國安, 郭慶偉, 等. 腸道菌群失調與感染性疾病關系的研究進展. 中國病原生物學雜志, 2025, 20(2): 262-266.
41.	Isler B, Welyczko Z, Jorgensen N, et al. Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence. Antimicrob Agents Chemother, 2025, 69(10): e0033825. doi: 10.1128/aac.00338-25.
42.	Hodzhev V, Dzhambazov K, Sapundziev N, et al. High-dose probiotic mix of Lactobacillus spp. , Bifidobacterium spp. , Bacillus coagulans, and Saccharomyces boulardii to prevent antibiotic-associated diarrhea in adults: a multicenter, randomized, double-blind, placebo-controlled trial. Open Forum Infect Dis, 2024, 11(11): ofae615. doi: 10.1093/ofid/ofae615.
43.	Davido B, Merrick B, Kuijper E, et al. How can the gut microbiome be targeted to fight multidrug-resistant organisms? Lancet Microbe, 2025, 6(8): 101063. doi: 10.1016/j.lanmic.2024.10106.

1. Patel R. Periprosthetic joint infection. N Engl J Med, 2023, 388(3): 251-262.
2. Nelson SB, Pinkney JA, Chen AF, et al. Periprosthetic joint infection: current clinical challenges. Clin Infect Dis, 2023, 77(7): e34-e45.
3. 張克石, 吳婕, 徐超, 等. 人工關節假體周圍感染的診斷標準沿革與技術進展. 中華骨與關節外科雜志, 2024, 17(11): 1007-1014.
4. 國家骨科醫學中心保膝聯盟, 中華醫學會骨科學分會保膝學組, 中國老年保健協會骨關節保護與健康分會, 等. 單髁置換術后假體周圍感染預防中國專家共識. 實用骨科雜志, 2025, 31(1): 1-14.
5. Kong L, Cao J, Zhang Y, et al. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. Int Wound J, 2017, 14(3): 529-536.
6. Li J, Liu Z, Wang Z, et al. Risk factors for periprosthetic joint infection following primary total knee arthroplasty: a systematic review and meta-analysis. Front Surg, 2026, 12: 1715571. doi: 10.3389/fsurg.2025.1715571.
7. Resende VAC, Neto AC, Nunes C, et al. Higher age, female gender, osteoarthritis and blood transfusion protect against periprosthetic joint infection in total hip or knee arthroplasties: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc, 2021, 29(1): 8-43.
8. Ren X, Ling L, Qi L, et al. Patients’ risk factors for periprosthetic joint infection in primary total hip arthroplasty: a meta-analysis of 40 studies. BMC Musculoskelet Disord, 2021, 22(1): 776. doi: 10.1186/s12891-021-04647-1.
9. Caballero-Flores G, Pickard JM, Nú?ez G. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat Rev Microbiol, 2023, 21(6): 347-360.
10. Liang L, Yang Z, Fu X. Ecology of the gut microbiota and colonization resistance: mechanisms and therapeutic implications. FEMS Microbiol Ecol, 2025, 102(1): fiaf124. doi: 10.1093/femsec/fiaf124.
11. Remily EA, Sax OC, Douglas SJ, et al. Inflammatory bowel disease is associated with increased complications after total knee arthroplasty. Knee, 2023, 40: 313-318.
12. Chisari E, D’Mello D, Sherman MB, Parvizi J. Inflammatory bowel diseases increase the risk of periprosthetic joint infection. J Bone Joint Surg (Am), 2022, 104(2): 160-165.
13. Krezalek MA, Hyoju S, Zaborin A, et al. Can methicillin-resistant Staphylococcus aureus silently travel from the gut to the wound and cause postoperative infection? Modeling the “Trojan horse” hypothesis. Ann Surg, 2018, 267(4): 749-758.
14. Hernandez CJ, Yang X, Ji G, et al. Disruption of the gut microbiome increases the risk of periprosthetic joint infection in mice. Clin Orthop Relat Res, 2019, 477(11): 2588-2598.
15. Levast B, Benech N, Gasc C, et al. Impact on the gut microbiota of intensive and prolonged antimicrobial therapy in patients with bone and joint infection. Front Med (Lausanne), 2021, 8: 586875. doi: 10.3389/fmed.2021.586875.
16. Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic hip and knee infection: An evidence-based and validated criteria. J Arthroplasty, 2018, 33(5): 1309-1314.
17. Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum, 1991, 34(5): 505-514.
18. Ji B, Aimaiti A, Wang F, et al. Intraoperative direct sonication of implants and soft tissue for the diagnosis of periprosthetic joint infection. J Bone Joint Surg (Am), 2023, 105(11): 855-864.
19. Li Y, Wang F, Wahafu T, et al. Intraoperative direct sonication versus conventional sonication in the diagnosis of periprosthetic joint infection: comparison of diagnostic accuracy and time to positivity of fluid culture. J Bone Joint Surg (Am), 2025, 107(13): 1439-1449.
20. 紀保超, 阿不都賽米·艾買提, 汪斐, 等. 非接觸式低頻超聲清創技術治療假體周圍感染早期效果的前瞻性單臂臨床研究. 中華外科雜志, 2023, 61(2): 129-137.
21. 謝政. 骨性關節炎患者腸道菌群結構特征及功能分析. 鄭州: 鄭州大學, 2020.
22. Longo UG, Lalli A, Bandini B, et al. The influence of gut microbiome on periprosthetic joint infections: state-of-the-art. J ISAKOS, 2024, 9(3): 353-361.
23. Ramasamy BR, Sharma DK, Callary SA, et al. Role of gut microbiota disruption in prosthetic joint infection: a scoping review. Lancet Microbe, 2025, 6(11): 101193. doi: 10.1016/j.lanmic.2025.101193.
24. Singlitico A, Grassa D, Kaplan R, et al. The hidden connection between gut microbiota and periprosthetic joint infections: a scoping review. J Bone Joint Infect, 2025, 10(2): 85-92.
25. Chisari E, Cho J, Wouthuyzen-Bakker M, et al. Gut permeability may be associated with periprosthetic joint infection after total hip and knee arthroplasty. Sci Rep, 2022, 12(1): 15094. doi: 10.1038/s41598-022-19034-6.
26. 中國食品科學技術學會益生菌分會. 人體腸道菌群主要特征的專家共識. 中國食品學報, 2024, 24(7): 460-470.
27. Zheng Y, Zhang Z, Tang P, et al. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front Immunol, 2023, 14: 1143548. doi: 10.3389/fimmu.2023.1143548.
28. Schlechte J, Zucoloto AZ, Yu IL, et al. Dysbiosis of a microbiota-immune metasystem in critical illness is associated with nosocomial infections. Nat Med, 2023, 29(4): 1017-1027.
29. Ducarmon QR, Zwittink RD, Hornung BVH, et al. Gut microbiota and colonization resistance against bacterial enteric infection. Microbiol Mol Biol Rev, 2019, 83(3): e00007-19.
30. 劉有才, 李筱蟠, 魏春根, 等. 腸道菌群失調對反復呼吸道感染患兒免疫功能的影響. 吉林醫學, 2022, 43(4): 938-939.
31. Fernandez Sanchez J, Maknojia AA, King KY. Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease. Blood, 2024, 143(17): 1689-1701.
32. Zhang D, Chen G, Manwani D, et al. Neutrophil ageing is regulated by the microbiome. Nature, 2015, 525(7570): 528-532.
33. Deshmukh HS, Liu Y, Menkiti OR, et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med, 2014, 20(5): 524-530.
34. Wells C, Robertson T, Sheth P, et al. How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation. Heliyon, 2024, 10(12): e32831. doi: 10.1016/j.heliyon.2024.e32831.
35. Khosravi A, Yá?ez A, Price JG, et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe, 2014, 15(3): 374-381.
36. Rashid MU, Zaura E, Buijs MJ, et al. Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota. Clin Infect Dis, 2015, 60(Suppl 2): S77-S84.
37. Stecher B, Maier L, Hardt WD. ‘Blooming’ in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol, 2013, 11(4): 277-284.
38. Wei Y, Palacios Araya D, Palmer KL. Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics. Nat Rev Microbiol, 2024, 22(11): 705-721.
39. Heckmann ND, Culler MW, Mont MA, et al. Emerging concepts in periprosthetic joint infection research: the human microbiome. J Arthroplasty, 2025, 40(7): 1821-1826.
40. 劉夢, 張國安, 郭慶偉, 等. 腸道菌群失調與感染性疾病關系的研究進展. 中國病原生物學雜志, 2025, 20(2): 262-266.
41. Isler B, Welyczko Z, Jorgensen N, et al. Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence. Antimicrob Agents Chemother, 2025, 69(10): e0033825. doi: 10.1128/aac.00338-25.
42. Hodzhev V, Dzhambazov K, Sapundziev N, et al. High-dose probiotic mix of Lactobacillus spp. , Bifidobacterium spp. , Bacillus coagulans, and Saccharomyces boulardii to prevent antibiotic-associated diarrhea in adults: a multicenter, randomized, double-blind, placebo-controlled trial. Open Forum Infect Dis, 2024, 11(11): ofae615. doi: 10.1093/ofid/ofae615.
43. Davido B, Merrick B, Kuijper E, et al. How can the gut microbiome be targeted to fight multidrug-resistant organisms? Lancet Microbe, 2025, 6(8): 101063. doi: 10.1016/j.lanmic.2024.10106.

Chinese Journal of Reparative and Reconstructive Surgery

Differential analysis of gut microbiome in patients with periprosthetic joint infection, aseptic failure, and osteoarthritis

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