Division of Rheumatology, HUG, Geneva, Switzerland
Geneva Centre for Inflammation Research, UNIGE, Geneva, Switzerland.
RMD Open. 2024 Jan 30;10(1):e003589. doi: 10.1136/rmdopen-2023-003589.
Faecal , and other microbes, have been associated with rheumatoid arthritis (RA) and preclinical RA. We have performed a quantitative microbiome profiling study in preclinical stages of RA.
First-degree relatives of patients with RA (RA-FDRs) from the SCREEN-RA cohort were categorised into four groups: controls, healthy asymptomatic RA-FDRs; high genetic risk, asymptomatic RA-FDRs with two copies of the shared epitope; autoimmunity, asymptomatic RA-FDRs with RA-associated autoimmunity; and symptomatic, clinically suspect arthralgias or untreated new-onset RA.Faecal samples were collected and frozen. 16S sequencing was performed, processed with DADA2 pipeline and Silva database. Cell counts (cytometry) and faecal calprotectin (enzyme-linked immunosorbent assay, ELISA) were also obtained. Microbial community analyses were conducted using non-parametric tests, such as permutational multivariate analysis of variance (PERMANOVA), Wilcoxon and Kruskal-Wallis, or Aldex2.
A total of 371 individuals were included and categorised according to their preclinical stage of the disease. Groups had similar age, gender and body mass index. We found no significant differences in the quantitative microbiome profiles by preclinical stages (PERMANOVA, R2=0.00798, p=0.56) and, in particular, no group differences in abundance. Results were similar when using relative microbiome profiling data (PERMANOVA, R2=0.0073, p=0.83) or Aldex2 on 16S sequence counts. Regarding faecal calprotectin, we found no differences between groups (p=0.3).
We could not identify microbiome profiles associated with preclinical stages of RA. Only in a subgroup of individuals with the most pronounced phenotypes did we modestly retrieve the previously reported associations.
粪便和其他微生物与类风湿关节炎（RA）和临床前 RA 有关。我们对 RA 的临床前阶段进行了定量微生物组谱研究。
从 SCREEN-RA 队列中，将 RA 患者的一级亲属（RA-FDR）分为四组：对照组、无症状 RA-FDR 健康人群；高遗传风险、具有两个共享表位的无症状 RA-FDR；自身免疫、具有 RA 相关自身抗体的无症状 RA-FDR；以及症状性、临床可疑关节炎或未经治疗的新发病 RA。收集和冷冻粪便样本。进行 16S 测序，用 DADA2 管道和 Silva 数据库进行处理。还获得了细胞计数（流式细胞术）和粪便钙卫蛋白（酶联免疫吸附试验，ELISA）。使用非参数检验（如置换多元方差分析（PERMANOVA）、Wilcoxon 和 Kruskal-Wallis 检验，或 Aldex2）进行微生物群落分析。
共纳入 371 名个体，并根据疾病的临床前阶段进行分类。各组的年龄、性别和体重指数相似。我们未发现临床前阶段的定量微生物组谱存在显著差异（PERMANOVA，R2=0.00798，p=0.56），特别是丰度上没有组间差异。当使用相对微生物组谱数据（PERMANOVA，R2=0.0073，p=0.83）或 Aldex2 对 16S 序列计数进行分析时，结果相似。关于粪便钙卫蛋白，我们发现各组之间没有差异（p=0.3）。
我们无法确定与 RA 临床前阶段相关的微生物组谱。仅在具有最明显表型的个体亚组中，我们才适度地恢复了之前报道的关联。
