Longitudinal changes in gut microbial evenness and dominance during anti-CD20-containing chemoimmunotherapy with concurrent trimethoprim–sulfamethoxazole prophylaxis in patients with B-cell lymphoma

Reduced gut microbial diversity is associated with adverse outcomes in hematological malignancies. However, longitudinal studies during lymphoma chemoimmunotherapy rarely distinguish richness from evenness. We investigated whether microbial diversity shifts during anti-CD20-containing chemoimmunotherapy reflect loss of detected taxa or redistribution of relative abundances. In this prospective, single-center exploratory study, 40 patients with B-cell lymphoma provided pretreatment stool samples and 18 paired post-treatment samples. All 18 participants received trimethoprim–sulfamethoxazole (TMP-SMX) prophylaxis from treatment initiation through post-treatment sampling, without additional systemic antibacterial exposure between collections or during the 3 months preceding baseline. Following 16S rRNA gene V3–V4 sequencing, Pielou’s evenness (q = 0.0077) and Shannon diversity (q = 0.0208) decreased post-treatment, whereas observed features and Faith’s phylogenetic diversity did not change significantly (q = 0.4923 and 0.7660, respectively). Dominance significantly increased (Simpson, q = 0.0154; Berger–Parker, q = 0.0237). Beta diversity showed no detectable compositional shift, no genus-level taxon met differential-abundance criteria, and newly dominant taxa varied across individuals. These changes accompanied the combined treatment exposure in a cohort that may overrepresent clinically stable patients; the chemoimmunotherapy and TMP-SMX contributions were inseparable. These alterations appear modest and predominantly structural, with the clearest changes in evenness and dominance, and substantial uncertainty about richness.