Conventional myelosuppressive chemotherapy for non-haematological malignancy disrupts the intestinal microbiome

BackgroundThe gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown.MethodsFaecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7-12days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing.ResultsCompared to pre-chemotherapy samples, samples collected 7-12days following chemotherapy exhibited increased richness (mean 120 observed species SD 38 vs 134 +/- 40; p=0.007) and diversity (Shannon diversity: mean 6.4 +/- 0.43 vs 6.6 +/- 0.41; p=0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p=0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p=0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p=0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle.Conclusions Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.

Automated summary

Conventional myelosuppressive chemotherapy results in significant changes in gut microbiota characteristics during the predicted myelosuppression period post-chemotherapy, but these changes are no longer significant at the end of the chemotherapy cycle. Further research is needed to link microbiome changes during chemotherapy to clinical outcomes.