BACKGROUND Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. RESULTS The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. CONCLUSION Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species.

中文翻译：

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肉芽肿性多血管炎中人鼻微生物组的组成和功能蛋白子系统：一项初步研究。

背景 肉芽肿性多血管炎 (GPA) 累及耳、鼻和喉咙通常是最初的疾病表现。先前的调查已经观察到 GPA 患者金黄色葡萄球菌的患病率较高，慢性鼻腔携带与疾病复发风险增加有关。在这项横断面研究中，我们调查了鼻腔微生物群的变化，包括对葡萄球菌属的详细分析。通过鸟枪宏基因组学研究患有活动性和非活动性肉芽肿性多血管炎 (GPA) 的患者。鸟枪法宏基因组序列数据还用于识别 SEED 数据库中的蛋白质编码基因，然后蛋白质的丰度与带注释的热图上细菌种类的存在相关联。结果 S 的存在。与非活动性 GPA (34.1%) 相比，在活动性 GPA 患者 (66.7%) 中，通过培养评估的鼻内金黄色葡萄球菌更常见。通过细菌 16S rRNA 分析对鼻腔微生物群进行的 Beta 多样性分析揭示了 GPA 患者和健康对照之间的不同组成（P = 0.039）。葡萄球菌属鸟枪法宏基因组序列数据的 Beta 多样性分析。揭示了活动 GPA 患者与健康对照和疾病对照之间的不同组成（分别为 P = 0.0007 和 P = 0.0023），以及健康对照与非活动 GPA 患者和家庭对照之间的不同组成（分别为 P = 0.0168 和 P = 0.0168）。具有活性 GPA 的患者具有更高丰度的金黄色葡萄球菌，反映了培养数据，而健康对照具有更高丰度的表皮葡萄球菌。假中间葡萄球菌，通常被认为是猫和狗的病原体，在葡萄球菌属中显示出 13% 的丰度。在我们的队列中。在对基线时 GPA 不活动的患者进行长期随访期间，较高的金黄色葡萄球菌丰度与复发风险增加无关。功能分析确定了 10 个在各组之间不同的 SEED 蛋白质子系统。最重要的关联与分支酸合成有关，并参与维生素 B12 途径。结论 我们的数据显示，与疾病和健康对照组相比，GPA 患者的鼻腔微生物群明显失调。宏基因组测序表明，活动性 GPA 患者的这种生态失调表现为金黄色葡萄球菌丰度增加和表皮葡萄球菌减少，进一步证明了这些物种之间的拮抗关系。SEED 功能蛋白子系统分析确定了主要见于 GPA 患者的独特细菌鼻腔微生物群与分支酸合成和维生素 B12 途径相关基因丰度升高之间的关联。需要进一步的研究来进一步阐明生物合成基因与相关细菌种类之间的关系。