Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis.
Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis.
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DOI：
10.1002/art.41723
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Merkel PA
中科院分区：
文献类型：
--
作者：
Rhee RL;Lu J;Bittinger K;Lee JJ;Mattei LM;Sreih AG;Chou S;Miner JJ;Cohen NA;Kelly BJ;Lee H;Grayson PC;Collman RG;Merkel PA
对于肉芽肿性多血管炎（GPA）中鼻腔细菌的时间变化知之甚少。我们研究了与 GPA 患者复发相关的鼻腔微生物群的纵向变化。对 19 名 GPA 患者的鼻拭子进行了细菌 16S 基因测序，纵向随访共 78 次就诊，其中 9 名患者出现复发，10 名患者仍处于缓解状态。检查细菌的相对丰度和细菌之间的比率。广义估计方程模型评估了细菌组成与 1) 疾病活动性和 2) PR3-ANCA 水平之间的关联，并根据药物进行了调整。棒状杆菌和葡萄球菌是所有鼻腔样本中最丰富的细菌属。静止期疾病患者在就诊期间棒状杆菌与葡萄球菌的比例保持稳定。相比之下，在经历复发的患者中，复发前就诊时的比率显着较低，随后复发时的比率较高（调整后 P < 0.01）。物种水平分析确定鼻腔结核杆菌的较高丰度与复发（调整后的 P = 0.04）和较高的 PR3-ANCA 水平（调整后的 P = 0.02）之间存在关联。在 GPA 中，随着时间的推移，鼻腔微生物组会发生显着变化，并且与疾病活动相关。这些变化在复发前几个月发生，支持鼻腔细菌在 GPA 中的致病作用。我们的结果支持了现有的假设，即葡萄球菌是疾病的诱发因素，并产生了一项新的发现，涉及棒状杆菌作为 GPA 疾病的潜在介质。
Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). We examined longitudinal changes in the nasal microbiome in association with relapse in GPA patients. Bacterial 16S gene sequencing was performed on nasal swabs of 19 patients with GPA followed longitudinally for a total of 78 visits, including 9 patients who developed a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models evaluated the association between bacterial composition and 1) disease activity and 2) PR3-ANCA level, adjusting for medications. Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio occurred at the visit prior to relapse, followed by a higher ratio at time of relapse (adjusted P < 0.01). Species-level analysis identified an association between higher abundance of nasal Corynebacterium tuberculostearicum and relapse (adjusted P = 0.04) and higher PR3-ANCA levels (adjusted P = 0.02). In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
16S rRNA基因扩增子测序的优势和局限性在揭示时间微生物群落动力学中。
影响因子：
3.7
作者：
Poretsky R;Rodriguez-R LM;Luo C;Tsementzi D;Konstantinidis KT
通讯作者：
Konstantinidis KT
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
影响因子：
6.4
作者：
Lemon, Katherine P.;Klepac-Ceraj, Vanja;Kolter, Roberto
通讯作者：
Kolter, Roberto
影响因子：
2.8
作者：
Indrigo, J;Hunter, RL;Actor, JK
通讯作者：
Actor, JK