Gut Dysbiosis Pattern in Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-analysis

Abstract BackgroundGut microbiota has emerged as a critical mediator of immune homeostasis and cancer biology. Increasing evidence suggests that gut dysbiosis may play a significant role in the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma (NHL). However, a comprehensive synthesis of the microbial alterations associated with DLBCL remains lacking.MethodsWe conducted a systematic review and meta-analysis of fourteen studies encompassing total 4,113 cases to evaluate the association between DLBCL and gut dysbiosis. A pooled effect estimate of depletion and abundance Odds Ratio (OR) was calculated, and microbial shifts were analyzed at the species level to contextualize biological relevance.Results Fourteen studies were included in our systematic review (8 observational and 6 mendelian randomization studies). Meta analysis was done for the six mendelian randomization studies (n = 3737 cases were included). The overall pooled OR was 0.96 (95% CI: 0.93–1.00), indicating a borderline association between bacterial taxa and DLBCL, with substantial heterogeneity (I² = 78.7%). Subgroup analyses by taxa revealed significant associations: Bilophila (OR = 1.78), Desulfovibrionaceae (OR = 1.58), and Coprobacter (OR = 1.37) were enriched in DLBCL, while Alistipes (OR = 0.57), Ruminococcaceae UCG011 (OR = 0.75), and Eubacterium coprostanoligenes group (OR = 0.19) were significantly depleted. These findings emphasize the importance of species-level analysis to uncover specific microbial associations with DLBCL.ConclusionsThis study supports a possible role of the gut microbiota in the pathogenesis of DLBCL, identifying both enriched and depleted taxa across multiple studies and emphasizing the importance of species-level analysis and underscore the need for further mechanistic and longitudinal studies.