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

Patients with R/RL showed increased relative abundances of Actinobacteriota and Alphaproteobacteria compared to primary treatment-naïve lymphoma patients.

• Study enrolled 21 patients total: 14 with R/RL and 7 with primary lymphoma (PL) as controls
• Gut microbiota profiling was conducted using 16S rDNA sequencing
• Pretreatment fecal samples were collected from all participants between November 2023 and December 2024
• Patients were enrolled at the Department of Lymphoma and Oncology, Shanxi Bethune Hospital

Patients with R/RL showed decreased levels of Erysipelotrichales, Morganellaceae, Faecalibacterium, Clostridium, Klebsiella, and Ruminococcus compared to PL patients.

• Differential abundance analysis was performed between R/RL and PL groups
• Alpha diversity, beta diversity, and species composition were all assessed via 16S rDNA sequencing
• Specific taxa including Faecalibacterium and Ruminococcus, known short-chain fatty acid producers, were reduced in R/RL patients

Seven metabolites were significantly upregulated in the R/RL group compared to PL patients.

• The seven upregulated metabolites were: 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)
• All metabolites met the significance threshold of p < 0.05
• Metabolites were identified using untargeted metabolomics methodology
• UDP-N-acetylglucosamine had the lowest p-value among the upregulated metabolites (p = 0.011)

KEGG pathway analysis indicated enhanced central carbon metabolism and amino acid metabolism in cancer among R/RL patients.

• Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was applied to differentially expressed metabolites
• Literature review corroborated the KEGG pathway findings
• Upregulated metabolites including isoleucine, glycine, and alanine are consistent with enhanced amino acid metabolism
• 2-hydroxybutyric acid and pantothenic acid are consistent with alterations in central carbon metabolism

The authors concluded that therapeutic modulation of gut microbiota, including fecal microbiota transplantation, may improve the intestinal immune microenvironment in R/RL patients.

• This conclusion was based on the observed alterations in gut microbiota composition and metabolic activity
• The authors stated the work is 'hypothesis-generating and requires large-scale validation'
• The study sample size was small (n = 21 total; n = 14 R/RL, n = 7 PL)
• The proposed mechanism is that gut microbiota alterations 'may contribute to the pathophysiology of R/RL'