The Role of Gut Microbiota and Their Derived Metabolites in Chemotherapy‐Induced Nausea and Vomiting in Ovarian Cancer
ABSTRACT
Objective
This study aimed to investigate the relationship between gut microbiota and chemotherapy‐induced nausea and vomiting (CINV) in patients with ovarian cancer undergoing platinum‐based chemotherapy (carboplatin or cisplatin combined with paclitaxel).
Methods
Clinical data and fecal samples were collected from patients with ovarian cancer after admission but prior to the initiation of their first chemotherapy cycle. Patients were divided into the CINV ( n = 25) and non‐CINV ( n = 25) groups on the basis of symptoms occurring after chemotherapy. No additional samples were collected during chemotherapy. Integrated metagenomic sequencing and untargeted metabolomic profiling identified CINV‐associated microbial taxa and metabolites. Additionally, fecal microbiota transplantation (FMT) in SD rats validated causal links between gut dysbiosis and CINV pathogenesis.
Results
Bacteroides caccae , Corynebacteriales, and Corynebacterium were significantly enriched in the CINV group. KEGG enrichment revealed upregulated pathways in CINV, including focal adhesion, lysosome function, and eukaryotic cellular communities. Metabolomic analysis identified 19 significantly increased metabolites in the fecal samples of CINV patients versus 10 in non‐CINV controls. KEGG enrichment revealed that the pentose phosphate pathway, glutathione metabolism, and lipoic acid metabolism were significantly implicated in CINV pathogenesis. Multi‐omics integration revealed Bacteroides sp. A1C1 strongly correlated with hesperetin, arbutin, orciprenaline, and myristolic acid. In rats, cisplatin‐induced CINV models showed higher kaolin consumption versus controls ( p < 0.05). FMT from non‐CINV donors reduced kaolin consumption in cisplatin‐treated rats ( p < 0.05). The expression of 5‐HT3R, NK1R, and NK2R in the medulla oblongata and colon was significantly increased in the cisplatin model group ( p < 0.05) and partially reversed by non‐CINV FMT ( p < 0.05).
Conclusions
Gut microbiota dysbiosis directly contributes to CINV pathogenesis. Bacteroides sp. A1C1 and its putatively identified metabolites (hesperetin, arbutin, orciprenaline, and myristolic acid) represent potential diagnostic biomarkers for CINV.