Rothman Orthopaedic Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA.
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sci Rep. 2022 Sep 5;12(1):15094. doi: 10.1038/s41598-022-19034-6.
A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system function and ultimately affecting the outcome of interventions. We hypothesized that the loss of mucosal barrier in the gut may be associatedto acute and chronic periprosthetic joint infections (PJI). Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) were tested in plasma as part of a prospective cohort study of patients undergoing primary arthroplasty or revision arthroplasty because of an aseptic failure or PJI (as defined by the 2018 criteria). All blood samples were collected before antibiotic administration. Samples were tested using commercially available enzyme-linked immunosorbent assays as markers for gut permeability. A total of 134 patients were included in the study of which 44 patients had PJI (30 chronic and 14 acute), and the remaining 90 patients were categorized as non-infected that included 64 patients revised for aseptic failure, and 26 patients undergoing primary total joint arthroplasty. Both Zonulin (7.642 ± 6.077 ng/mL vs 4.560 ± 3.833 ng/mL; p < 0.001) and sCD14 levels (555.721 ± 216.659 ng/mL vs 396.872 ± 247.920 ng/mL; p = 0.003) were significantly elevated in the PJI group compared to non-infected cases. Higher levels of Zonulin were found in acute infections compared to chronic PJI (11.595 ± 6.722 ng/mL vs. 5.798 ± 4.841 ng/mL; p = 0.005). This prospective study reveals a possible link between gut permeability and the 'gut-immune-joint axis' in PJI. If this association continues to be borne out with a larger cohort and more in-depth analysis, it will have a clinically significant implication in managing patients with PJI. It may be that in addition to the administration of antimicrobials, patients with PJI and other orthopaedic infections may benefit from administration of gastrointestinal modulators such as pro and prebiotics.
越来越多的近期研究表明，人类基因组、肠道微生物组和蛋白质组学表明，黏膜屏障功能的丧失，特别是在胃肠道中，可能会极大地影响抗原运输，最终影响肠道微生物组和免疫系统之间的密切双向相互作用。这种串扰在塑造宿主免疫系统功能方面具有重要影响，并最终影响干预的结果。我们假设肠道黏膜屏障的丧失可能与急性和慢性人工关节周围感染（PJI）有关。我们在一项接受初次关节置换或翻修关节置换的患者前瞻性队列研究中，以血浆中的封闭蛋白、可溶性 CD14（sCD14）和脂多糖（LPS）作为标志物进行了测试，因为这些患者出现无菌性失败或 PJI（根据 2018 年标准定义）。所有血液样本均在使用抗生素之前采集。使用商业上可获得的酶联免疫吸附试验对样本进行测试，以检测肠道通透性标志物。共纳入 134 例患者，其中 44 例为 PJI（30 例慢性和 14 例急性），其余 90 例为非感染患者，包括 64 例无菌性失败患者和 26 例初次全关节置换术患者。与非感染患者相比，PJI 组的封闭蛋白（7.642±6.077ng/ml 比 4.560±3.833ng/ml；p＜0.001）和 sCD14 水平（555.721±216.659ng/ml 比 396.872±247.920ng/ml；p=0.003）显著升高。与慢性 PJI 相比，急性感染中封闭蛋白水平更高（11.595±6.722ng/ml 比 5.798±4.841ng/ml；p=0.005）。这项前瞻性研究揭示了肠道通透性与 PJI 中的“肠道-免疫-关节轴”之间可能存在联系。如果随着更大的队列和更深入的分析，这种关联继续得到证实，那么它将对 PJI 患者的管理具有重要的临床意义。除了使用抗生素外，PJI 和其他骨科感染患者可能还会受益于胃肠道调节剂的治疗，如益生菌和益生元。
