Bellocchi Chiara, Fernández-Ochoa Álvaro, Montanelli Gaia, Vigone Barbara, Santaniello Alessandro, Quirantes-Piné Rosa, Borrás-Linares Isabel, Gerosa Maria, Artusi Carolina, Gualtierotti Roberta, Segura-Carrettero Antonio, Alarcón-Riquelme Marta E, Beretta Lorenzo
Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy.
Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
J Clin Med. 2019 Aug 23;8(9):1291. doi: 10.3390/jcm8091291.
Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE ( = 27), SjS ( = 23), PAPs ( = 11) and undifferentiated connective tissue (UCTD, = 26) patients, and geographically-matched healthy controls (HCs, = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.
菌群失调在系统性自身免疫性疾病（SADs）中已有报道，包括系统性红斑狼疮（SLE）、干燥综合征（SjS）和原发性抗磷脂综合征（PAPS），然而这些关联的生物学意义往往难以捉摸。收集了114名受试者的粪便和血浆样本，包括SLE患者（n = 27）、SjS患者（n = 23）、PAPS患者（n = 11）和未分化结缔组织病（UCTD，n = 26）患者，以及地理位置匹配的健康对照（HCs，n = 27），用于微生物组（16s rRNA基因测序）和代谢组（高效液相色谱-质谱联用）分析，以确定不同疾病间的共同特征。在130个已鉴定的微生物属中，29种细菌的子集能够区分研究组（受试者工作特征曲线下面积（AUROC）= 0.730±0.025）。从254个代谢峰中选取41个代谢峰的子集可获得较好的分类效果（AUROC = 0.748±0.021）。在这两个模型中，HCs与SADs能很好地区分开，而UCTD与其他疾病在很大程度上重叠。在所有SADs中，促耐受性细菌减少，而致病共生菌属增加。代谢改变包括两个聚类：（a）酰基肉碱家族成员，与普雷沃菌富集聚类呈正相关，与产丁酸细菌富集聚类呈负相关；（b）磷脂，与产丁酸细菌呈负相关。这些发现表明SADs患者肠道微生物群与代谢功能之间存在强烈的相互作用。
