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

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-naïve, 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 (n = 106) with additional samples. We compared the microbiome data from these patients with those of 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 < 0.001), and the microbial composition differed significantly between the groups (P < 0.001). The abundance of 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 < 0.001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = 0.007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = 0.035) and interferon-g (P = 0.045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.