Abstract
Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment.