Alterations in Gut Microbiota and Metabolic Profiles in Relapsed or Refractory Lymphoma.

To identify potential therapeutic strategies for relapsed or refractory lymphoma (R/RL) by examining differences in gut microbiota composition and metabolic profiles between patients with R/RL and those with primary, treatment-naïve lymphoma (PL), using fecal microbiota analysis and metabolomics. A total of 21 patients with lymphoma were enrolled at the Department of Lymphoma and Oncology, Shanxi Bethune Hospital, between November 2023 and December 2024. The cohort included 14 patients with R/RL and 7 with PL, who served as the control group. Pretreatment fecal samples and clinical data were collected from all participants. Gut microbiota profiling was conducted using 16S rDNA sequencing, including alpha diversity, beta diversity, species composition, and differential abundance. Untargeted metabolomics was employed to identify and analyze differentially expressed metabolites between the groups. Patients with R/RL exhibited increased relative abundances of Actinobacteriota and Alphaproteobacteria and decreased levels of Erysipelotrichales, Morganellaceae, Faecalibacterium, Clostridium, Klebsiella, and Ruminococcus. Seven metabolites were significantly upregulated in the R/RL group (p < 0.05): 3-amino-4-methylpentanoic acid (p = 0.028), 2-hydroxybutyric acid (p = 0.020), UDP-N-acetylglucosamine (UDP-N-AG) (p = 0.011), pantothenic acid (p = 0.037), isoleucine (p = 0.028), glycine (p = 0.044), and alanine (p = 0.025). Literature review and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated enhanced central carbon metabolism and amino acid metabolism in cancer. Alterations in gut microbiota and metabolic activity may contribute to the pathophysiology of R/RL. Therapeutic modulation of the gut microbiota, including the use of fecal microbiota transplantation, may improve the intestinal immune microenvironment in this patient population. The present work is hypothesis-generating and requires large-scale validation.