Table_13_Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis.xlsx

BackgroundEmerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis.
MethodsTo characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis.
ResultsThere were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis.
ConclusionsFor the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

研究背景：越来越多的研究证据表明，肠道菌群失调与浆细胞病及淀粉样沉积疾病的发生发展密切相关，但目前尚无关于肠道菌群与免疫球蛋白轻链（AL）淀粉样变性之间关联的相关研究数据。
研究方法：为明确AL淀粉样变性患者的肠道菌群特征，本研究收集了27例AL淀粉样变性患者以及27例年龄、性别、体质量指数（BMI）相匹配的健康对照者的粪便样本，采用16S rRNA MiSeq测序技术进行测序，并基于扩增子序列变异（ASV）开展菌群分析。
研究结果：两组受试者的肠道菌群群落结构存在显著差异。在门水平上，AL淀粉样变性患者的放线菌门（Actinobacteriota）和疣微菌门（Verrucomicrobiota）的丰度显著升高，而拟杆菌门（Bacteroidota）的丰度显著降低。在属水平上，AL淀粉样变性患者体内的17个菌属（包括双歧杆菌属、Akkermansia属、链球菌属）富集，而仅4个菌属（包括粪杆菌属、Tyzzerella属、假单胞菌属、Anaerostignum属）的丰度显著下降。值得注意的是，本研究筛选出5个基于ASV的最优微生物标志物用于构建AL淀粉样变性的诊断模型，训练集和测试集的曲线下面积（AUC）分别为0.8549（95%置信区间：0.7310~0.9789）和0.8025（95%置信区间：0.5771~1）。在中位随访时长为19.0个月的情况下，进一步的亚组分析显示，部分关键肠道微生物标志物与AL淀粉样变性患者的疾病严重程度、治疗应答甚至预后密切相关。
研究结论：本研究首次明确了AL淀粉样变性患者的肠道菌群失调特征，并成功构建并验证了基于微生物标志物的诊断模型，该成果为未来开展针对AL淀粉样变性患者的微生物靶向诊断与治疗策略相关研究提供了重要支撑。