Andréasson Kristofer, Alrawi Zaid, Persson Anita, Jönsson Göran, Marsal Jan
Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Section of Infectious Diseases, Department of Clinical Sciences, Lund University, Lund, Sweden.
Arthritis Res Ther. 2016 Nov 29;18(1):278. doi: 10.1186/s13075-016-1182-z.
Recent evidence suggests a link between autoimmunity and the intestinal microbial composition in several rheumatic diseases including systemic sclerosis (SSc). The objective of this study was to investigate the prevalence of intestinal dysbiosis in SSc and to characterise patients suffering from this potentially immunomodulatory deviation.
This study consisted of 98 consecutive patients subject to in-hospital care. Stool samples were analysed for intestinal microbiota composition using a validated genome-based microbiota test (GA-map™ Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota dysbiosis was found present as per this standardised test. Patients were examined regarding gastrointestinal and extraintestinal manifestations of SSc by clinical, laboratory, and radiological measures including esophageal cineradiography, the Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal inflammation).
A majority (75.5%) of the patients exhibited dysbiosis. Dysbiosis was more severe (r = 0.31, p = 0.001) and more common (p = 0.013) in patients with esophageal dysmotility. Dysbiosis was also more pronounced in patients with abnormal plasma levels of transthyretin (p = 0.045) or micronutrient deficiency (p = 0.009). In 19 patients at risk for malnutrition according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients with a negative dysbiosis test, only one was at risk for malnutrition. The mean ± SEM levels of F-calprotectin were 112 ± 14 and 45 ± 8 μg/g in patients with a positive and negative dysbiosis test, respectively. Dysbiosis was more severe in patients with skin telangiectasias (p = 0.020), pitting scars (p = 0.023), pulmonary fibrosis (p = 0.009), and elevated serum markers of inflammation (p < 0.001). However, dysbiosis did not correlate with age, disease duration, disease subtype, or extent of skin fibrosis.
In this cross-sectional study, intestinal dysbiosis was common in patients with SSc and was associated with gastrointestinal dysfunction, malnutrition and with some inflammatory, fibrotic and vascular extraintestinal features of SSc. Further studies are needed to elucidate the potential causal relationship of intestinal microbe-host interaction in this autoimmune disease.
最近的证据表明，自身免疫与包括系统性硬化症（SSc）在内的几种风湿性疾病的肠道微生物组成之间存在联系。本研究的目的是调查SSc患者肠道菌群失调的患病率，并对患有这种潜在免疫调节偏差的患者进行特征描述。
本研究纳入了98例连续住院治疗的患者。使用经过验证的基于基因组的微生物群测试（GA-map™菌群失调测试，挪威奥斯陆遗传分析公司）对粪便样本进行肠道微生物群组成分析。根据该标准化测试发现存在肠道微生物群失调。通过临床、实验室和放射学检查手段，包括食管动态造影、营养不良通用筛查工具（MUST）、血浆转甲状腺素（营养不良标志物）水平和粪便（F-）钙卫蛋白（肠道炎症标志物），对患者进行SSc胃肠道和肠外表现的检查。
大多数（75.5%）患者表现出菌群失调。食管动力障碍患者的菌群失调更为严重（r = 0.31，p = 0.001）且更为常见（p = 0.013）。转甲状腺素血浆水平异常（p = 0.045）或微量营养素缺乏（p = 0.009）的患者菌群失调也更明显。根据MUST，19例有营养不良风险的患者中有18例表现出菌群失调。相反，在24例菌群失调测试为阴性的患者中，只有1例有营养不良风险。菌群失调测试阳性和阴性患者的F-钙卫蛋白平均±标准误水平分别为每克1,12±14微克和45±8微克。皮肤毛细血管扩张（p = 0.020）、点状瘢痕（p = 0.023）、肺纤维化（p = 0.009）和炎症血清标志物升高（p < 0.001）的患者菌群失调更为严重。然而，菌群失调与年龄、病程、疾病亚型或皮肤纤维化程度无关。
在这项横断面研究中，肠道菌群失调在SSc患者中很常见，并且与胃肠道功能障碍、营养不良以及SSc的一些炎症、纤维化和血管性肠外特征相关。需要进一步研究以阐明这种自身免疫性疾病中肠道微生物与宿主相互作用的潜在因果关系。
