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

[BACKGROUND] Gut 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.

[METHODS] We 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.

[RESULTS] Meta 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 (I = 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.

[CONCLUSIONS] This 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.