AUTHOR=Yan Jipeng , Zhao Jin , Ning Xiaoxuan , Qin Yunlong , Xing Yan , Wang Yuwei , Jia Qing , Huang Boyong , Ma Rui , Lei Changhui , Zhou Meilan , Yu Zixian , Zhang Yumeng , Guo Wei-Feng , Sun Shiren 

TITLE=Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.973760

DOI=10.3389/fimmu.2022.973760

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Emerging 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.</p></sec><sec><title>Methods</title><p>To 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.</p></sec><sec><title>Results</title><p>There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of <italic>Actinobacteriota</italic> and <italic>Verrucomicrobiota</italic> was significantly higher, while <italic>Bacteroidota</italic> reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including <italic>Bifidobacterium</italic>, <italic>Akkermansia, and Streptococcus</italic> were enriched, while only 4 genera including <italic>Faecalibacterium</italic>, <italic>Tyzzerella</italic>, <italic>Pseudomonas</italic>, and <italic>Anaerostignum</italic> 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.</p></sec><sec><title>Conclusions</title><p>For 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.</p></sec>