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

## TL;DR

This study explores how gut bacteria and metabolic changes differ in patients with relapsed or refractory lymphoma compared to those with newly diagnosed lymphoma, suggesting potential new treatment strategies.

## Contribution

The study identifies specific gut microbiota and metabolic alterations in relapsed/refractory lymphoma patients, proposing gut microbiota modulation as a novel therapeutic approach.

## Key findings

- Patients with relapsed/refractory lymphoma showed increased Actinobacteriota and Alphaproteobacteria, and decreased Faecalibacterium and Clostridium.
- Seven metabolites were significantly upregulated in relapsed/refractory lymphoma, including 3-amino-4-methylpentanoic acid and pantothenic acid.
- Altered gut microbiota and metabolic profiles suggest a role in lymphoma pathophysiology and potential for fecal microbiota transplantation as therapy.

## Abstract

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.

Metabolomic volcano‐heatmap reveals seven upregulated metabolites in relapsed/refractory lymphoma, underscoring gut metabolic reprogramming as a potential therapeutic target.