Mutational Pattern Induced by 5-Fluorouracil and Oxaliplatin in the Gut Microbiome

Area of Science:

• Microbiology
• Genomics
• Pharmacology

Background:

• Chemotherapeutic agents, including 5-fluorouracil (5-FU) and oxaliplatin (Oxi), impact gut microbiota, but their interactions are not well understood.
• Understanding these drug-microbiota interactions is crucial for managing chemotherapy side effects and efficacy.

Purpose of the Study:

• To investigate the mutagenesis and proliferation effects of 5-FU and Oxi on gut microbiota.
• To analyze the interaction between these chemotherapeutic agents and gut microbiota during chemotherapy.
• To characterize the role of microbes and drug-microbe interactions in the gut microbiota's response to chemotherapy.

Main Methods:

• Development of a framework for taxonomy composition and genomic variation analysis.
• Analysis of gut microbiome data from chemotherapy patients.
• Detection and analysis of genetic variations and mutation signatures in gut microbiota.

Main Results:

• Over 1.45 million genetic variations were detected, significantly affecting gut microbiota mutation signatures.
• Oxaliplatin (Oxi) increased transversion rates, while 5-fluorouracil (5-FU) reduced them.
• Observed drug-associated shifts in bacteriome composition and functional alterations, including changes in nutrient metabolism and enrichment of specific biosynthesis pathways.

Conclusions:

• Chemotherapeutic agents exert significant selection pressure on gut microbiota, altering their genomic variation and functional profiles.
• Gut microbiota may play a role in chemotherapy efficacy, for example, by influencing cancer cell autophagy via NAD+ metabolism.
• This study provides a framework for understanding drug-microbe interactions in the context of chemotherapy.