Gut microbial dysbiosis appears to play a role in the development of diffuse large B-cell lymphoma (DLBCL) and its responsiveness to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), according to research published in Blood. Enterobacteriaceae-family members also appear to be more abundant in patients with febrile neutropenia and those with disease relapse or progression after therapy.

Previous research has shown that gut microbial dysbiosis plays a major role in innate and adaptive immunity. Chronic inflammation, a potential consequence of dysbiosis, may lead to both a greater risk of developing cancer and lead to a worse response to anticancer treatment.

In the DLBCL space, 16S ribosomal RNA (rRNA) gene and whole-genome shotgun (WGS) sequencing has shown that patients are likely to display dysbiosis involving proteobacteria-phylum members. It was, however, previously unestablished whether microbial dysbiosis has an effect on treatment outcomes.


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In particular, it was unknown whether gut microbiota influence response to R-CHOP. For this study, researchers conducted rRNA and WGS sequencing to determine any link between gut microbial dysbiosis and R-CHOP treatment outcomes among patients with DLBCL.

Overall, information from 189 patients was included in this study; samples from 158 patients underwent 16S rRNA sequencing, while 106 underwent WGS sequencing. In the overall cohort, 63% of patients were male sex, 48% of patients were older than 60 years, and 96% of patients had no evidence of B symptoms. After R-CHOP therapy, 90% of patients had a complete response, 21% of patients had febrile neutropenia, and 11% had a relapse during the follow-up period.

Compared with healthy controls, patients with DLBCL had lower alpha diversity (P <.001) and different microbial composition (P <.001). Enterobacteriaceae–family members (part of the proteobacteria phylum) were also more abundant in patients with DLBCL, and were linked with febrile neutropenia and relapse/progression (P <.001). Progression-free survival was also worse among those with greater Enterobacteriaceae abundance (P =.007).

Opportunistic pathogenesis occurred through type 1 pili, biofilm formation, and antibiotics resistance among patients.

“The possible role of the gut microbiota in the occurrence of febrile neutropenia and its influence on treatment outcomes should be clarified to improve the outcomes of patients with DLBCL receiving [R-CHOP] chemotherapy,” the authors wrote in their report.

Reference

Yoon SE, Kang W, Choi S, et al. The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma. Blood. 2023;141(18):2224-2238. doi:10.1182/blood.2022018831