The microbiome-lymphoma Axis: A systematic review and Meta-analysis of gut Dysbiosis pattern in diffuse large B-cell lymphoma

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 of diffuse large B-cell lymphoma (DLBCL), the most common and aggressive subtype of non-Hodgkin lymphoma (NHL). However, a comprehensive synthesis of the microbial alterations associated with DLBCL remains poorly defined. MethodsWe systematically reviewed and meta-analyzed thirteen studies (n = 4087 cases) to assess gut microbiota alterations in DLBCL. Both observational and Mendelian randomization designs were included. Pooled odds ratios (OR) were calculated for mendelian randomization studies using random-effects models, and microbial shifts were analyzed at the species level to contextualize biological relevance. Observational studies were used for qualitative assessment. ResultsMeta analysis was done for the mendelian randomization studies (n = 3737 cases). The overall pooled OR was 0.96 (95 % CI: 0.93–1.00), suggested a slight shift towards depletion, with considerable heterogeneity (I2 = 78.7 %). Species-level analysis revealed significant enrichment of pro-inflammatory or potentially oncogenic taxa in DLBCL, including Bilophila (OR = 1.78), Desulfovibrionaceae (OR = 1.58), and Coprobacter (OR = 1.37). Conversely, beneficial commensals with anti-inflammatory and metabolic regulatory roles such as Eubacterium coprostanoligenes group (OR = 0.19), Alistipes (OR = 0.57), Ruminococcaceae UCG011 (OR = 0.75) were significantly depleted. ConclusionsThis first comprehensive synthesis demonstrates a reproducible species-level microbial signature in DLBCL, characterized by depletion of protective commensals and enrichment of pro-tumorigenic taxa. Mechanistically, these shifts may promote lymphomagenesis via inflammatory, metabolic, and immune-modulatory pathways. Our findings highlight the gut microbiota as a latent biomarker source and therapeutic target, supporting microbiota-modulating strategies in precision lymphoma care.