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扁桃体微生物群的改变通过使衰老的中性粒细胞发生偏向,从而影响银屑病中的免疫反应。

Tonsillar microbiota alterations contribute to immune responses in psoriasis by skewing aged neutrophils.

作者信息

Chen Jiaoling, Liu Xuan, Bai Yaxing, Tang Xin, Xue Ke, Zhu Zhenlai, Liu Wanting, Wang Jiaqi, Wang Caiyu, Qiao Hongjiang, Dang Erle, Yin Wen, Wang Gang, Shao Shuai

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Br J Dermatol. 2025 Jul 17;193(2):310-321. doi: 10.1093/bjd/ljaf134.


DOI:10.1093/bjd/ljaf134
PMID:40228816
Abstract

BACKGROUND: The interplay between microbiota and the onset of immune-mediated diseases is increasingly coming to light. However, the role of tonsillar microbiota in cutaneous inflammation remains largely unknown. OBJECTIVES: To determine how the tonsillar microbiota influences skin inflammation in psoriasis and to uncover the underlying molecular mechanisms. METHODS: Tonsillar microbiota samples were collected from 24 healthy control individuals and 28 patients with psoriasis. Microbial community composition was analysed with 16S rRNA and metagenomic sequencing. Serum levels of short-chain fatty acids (SCFAs) were measured via liquid chromatography-mass spectrometry in 10 healthy control participants and 14 patients with psoriasis. Peripheral blood neutrophils from both groups were then exposed to a representative microbial metabolite and key proinflammatory markers evaluated using functional immune assays. RESULTS: We found significant alterations in the diversity and composition of the tonsillar microbial community in patients with psoriasis, with an increased prevalence of Bacteroidales and a decreased prevalence of Burkholderiales, Micrococcales and Pasteurellales relative to healthy control participants. Notably, a marked reduction in Rothia mucilaginosa correlated inversely with systemic inflammation (neutrophil-to-lymphocyte ratio) and disease severity (Psoriasis Area and Severity Index). Metagenomic analysis revealed disruptions in pathways critical to SCFA production, including propanoate, pyruvate and butanoate metabolism, which was supported by the significantly lower serum SCFA levels found in patients with psoriasis. Functional assays demonstrated that SCFAs inhibited neutrophil ageing, proinflammatory cytokine secretion and neutrophil extracellular trap formation. CONCLUSIONS: Our findings reveal that changes in tonsillar microbiota and their metabolic outputs contribute to psoriasis by modulating -immune responses, with potential clinical implications.

摘要

背景:微生物群与免疫介导疾病的发病之间的相互作用日益受到关注。然而,扁桃体微生物群在皮肤炎症中的作用在很大程度上仍不清楚。 目的:确定扁桃体微生物群如何影响银屑病中的皮肤炎症,并揭示潜在的分子机制。 方法:从24名健康对照个体和28名银屑病患者中收集扁桃体微生物群样本。使用16S rRNA和宏基因组测序分析微生物群落组成。通过液相色谱-质谱法测量10名健康对照参与者和14名银屑病患者的血清短链脂肪酸(SCFA)水平。然后将两组的外周血中性粒细胞暴露于一种代表性的微生物代谢产物,并使用功能性免疫测定法评估关键的促炎标志物。 结果:我们发现银屑病患者扁桃体微生物群落的多样性和组成有显著改变,与健康对照参与者相比,拟杆菌目患病率增加,伯克霍尔德菌目、微球菌目和巴斯德菌目患病率降低。值得注意的是,黏液罗氏菌的显著减少与全身炎症(中性粒细胞与淋巴细胞比率)和疾病严重程度(银屑病面积和严重程度指数)呈负相关。宏基因组分析揭示了对SCFA产生至关重要的途径的破坏,包括丙酸、丙酮酸和丁酸代谢,这得到了银屑病患者血清SCFA水平显著降低的支持。功能测定表明,SCFAs抑制中性粒细胞衰老、促炎细胞因子分泌和中性粒细胞胞外陷阱形成。 结论:我们的研究结果表明,扁桃体微生物群的变化及其代谢产物通过调节免疫反应导致银屑病,具有潜在的临床意义。

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