The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma

•Treatment-naive, newly diagnosed patients with DLBCL exhibited gut microbial dysbiosis.•The abundance of Enterobacteriaceae correlated with treatment outcome and febrile neutropenia after RCHOP chemotherapy. [Display omitted] The gut microbiome influences cancer development and the efficacy and saf...

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Published in:Blood 2023-05, Vol.141 (18), p.2224-2238
Main Authors: Yoon, Sang Eun, Kang, Woorim, Choi, Seunghyun, Park, Yoon, Chalita, Mauricio, Kim, Hyun, Lee, Je Hee, Hyun, Dong-Wook, Ryu, Kyung Ju, Sung, Hojun, Lee, Jae-Yun, Bae, Jin-Woo, Kim, Won Seog, Kim, Seok Jin
Format: Article
Language:English
Subjects:
Dysbiosis - complications
Febrile Neutropenia
Feces - microbiology
Gastrointestinal Microbiome
Humans
Lymphoma, Large B-Cell, Diffuse - complications
Lymphoma, Large B-Cell, Diffuse - drug therapy
Neoplasm Recurrence, Local
RNA, Ribosomal, 16S - analysis
RNA, Ribosomal, 16S - genetics
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Summary:•Treatment-naive, newly diagnosed patients with DLBCL exhibited gut microbial dysbiosis.•The abundance of Enterobacteriaceae correlated with treatment outcome and febrile neutropenia after RCHOP chemotherapy. [Display omitted] The gut microbiome influences cancer development and the efficacy and safety of chemotherapy but little is known about its effects on lymphoma. We obtained stool samples from treatment-naive, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing on additional samples (n = 106). We compared the microbiome data from these patients with data from healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < .001), and the microbial composition differed significantly between the groups (P < .001). The abundance of the Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P 
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2022018831