Bae Sangmee Sharon, Dong Tien S, Wang Jennifer, Lagishetty Venu, Katzka William, Jacobs Jonathan P, Charles-Schoeman Christina
University of California, Los Angeles School of Medicine, Los Angeles.
David Geffen School of Medicine at University of California, Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles.
ACR Open Rheumatol. 2022 Aug;4(8):658-670. doi: 10.1002/acr2.11436. Epub 2022 May 26.
The study objective was to compare the microbial composition of patients with dermatomyositis (DM) and healthy controls (HCs) and determine whether microbial alterations are associated with clinical manifestations of DM.
The 16S ribosomal RNA gene sequencing was performed on fecal samples from patients with DM and HCs. Microbial composition and diversity were compared between subjects with DM and HCs and in association with several DM-specific clinical variables, including myositis-specific autoantibodies (MSAs). Differentially abundant microbial taxa and genes associated with clinical characteristics were identified, and functional analysis was performed using predicted metagenomics. Dietary intake was assessed using a 24-hour dietary recall.
The fecal microbiome of 36 patients with DM and 26 HCs were analyzed. Patients with DM trended toward lower microbial diversity compared with HCs. The higher physician global damage score was significantly correlated with the lower microbial diversity in patients with DM. Patients with interstitial lung disease (ILD)-associated MSA (antisynthetase antibody (ab), anti-melanoma differentiation-associated protein 5 ab, n = 12) had significant differences in microbial composition and lower microbial diversity compared with HCs. Differential abundance testing demonstrated a unique taxonomic signature in the ILD-MSA subgroup, and predictive metagenomics identified functional alterations in a number of metabolic pathways. A significant increase in the relative abundance of Proteobacteria was positively correlated with multiple pathways involved in lipopolysaccharide synthesis and transport in the ILD-MSA group.
Patients with DM, particularly with ILD-associated MSAs, have lower microbial diversity and a distinct taxonomic composition compared with HCs. Further studies are needed to validate our findings and elucidate specific pathogenetic mechanisms that link the gut microbiome to clinical and pathological features of DM.
本研究旨在比较皮肌炎（DM）患者与健康对照者（HCs）的微生物组成，并确定微生物改变是否与DM的临床表现相关。
对DM患者和HCs的粪便样本进行16S核糖体RNA基因测序。比较DM患者和HCs之间的微生物组成和多样性，并将其与多个DM特异性临床变量相关联，包括肌炎特异性自身抗体（MSAs）。鉴定出与临床特征相关的差异丰富微生物分类群和基因，并使用预测宏基因组学进行功能分析。通过24小时饮食回顾评估饮食摄入量。
分析了36例DM患者和26例HCs的粪便微生物组。与HCs相比，DM患者的微生物多样性呈下降趋势。DM患者中，较高的医生整体损伤评分与较低的微生物多样性显著相关。与HCs相比，患有间质性肺病（ILD）相关MSA（抗合成酶抗体（ab）、抗黑色素瘤分化相关蛋白5 ab，n = 12）的患者在微生物组成上存在显著差异，且微生物多样性较低。差异丰度测试显示ILD-MSA亚组具有独特的分类特征，预测宏基因组学确定了多个代谢途径中的功能改变。在ILD-MSA组中，变形菌门相对丰度的显著增加与脂多糖合成和转运所涉及的多个途径呈正相关。
与HCs相比，DM患者，尤其是患有ILD相关MSAs的患者，微生物多样性较低，且具有独特的分类组成。需要进一步研究来验证我们的发现，并阐明将肠道微生物群与DM的临床和病理特征联系起来的具体致病机制。
