Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer

Abstract

Background: Chemotherapy induced diarrhea (CID) is a common side effect in patients receiving chemotherapy for cancer. The aim of our study was to explore the association between gut microorganisms and CID from the CapeOX regimen in resected stage III colorectal cancer (CRC) patients.

Results: After screening and identification, 17 stool samples were collected from resected stage III CRC patients undergoing the CapeOX regimen. Bacterial 16S ribosomal RNA genes was sequenced, and a bioinformatics analysis was executed to screen for the distinctive gut microbiome and the functional metabolism associated with CID due to the CapeOX regimen. The gut microbial community richness and community diversity were lower in CID (p < 0.05 vs control group). Klebsiella pneumoniae was the most predominant species (31.22%) among the gut microbiome in CRC patients with CID. There were 75 microorganisms with statistically significant differences at the species level between the CRC patients with and without CID (LDA, linear discriminant analysis score > 2), and there were 23 pathways that the differential microorganisms might be involved in.

Conclusions: The gut microbial community structure and diversity have changed in CRC patients with CID. It may provide novel insights into the prevention and treatment of CID.

Keywords: CapeOX; Chemotherapy; Colorectal cancer; Diarrhea; Microbiome.

Fig. 1

Study strategy. After screening and identification, finally, 17 stage III CRC patients undergoing the CapeOX regimen after curative resection were recruited into the present study. Stool samples were collected from the recruited patients. The bacterial 16S ribosomal RNA from the samples were sequenced. Bioinformatics analysis was used to analyze the distinctive gut microbiome and functional metabolism

Fig. 2

Microbial community structure analysis. The distribution of microorganisms from the same group was merged into the whole. The stacked bar graph was used to describe the distribution of microorganisms at the species level. CID- and CID+ represent the control group and experimental group, respectively

Fig. 3

Differential microbes analysis. The samples were divided into two groups according to patients with or without CID. The number of OTUs that were exclusive or shared by the two groups were visualized by a Venn Chart (a). The strip figure in b displays the LDA effect size analysis. LDA effect size analysis was used to compare the differences in microbial abundance between the two groups (b). LDA scores over 2 mean that the differences are statistically significant (p < 0.05). The cladogram in c displays the composition and proportion of microorganisms at different taxonomic levels. The innermost layer shows the taxonomic tree. The circle from the inside to the outside represents different taxon levels from phylum to genus. Yellow circles represent no statistical difference in species between the two groups, and red circles and green circles represent the higher abundance of genus in the control group and the chemotherapy-induced diarrhea group, respectively. The lowercase English letters corresponding to the different bacteria are shown in the legends

Fig. 4

Functional analysis. The Picrust software was used to analyze the pathway based on the KEGG database. The significant differences in functional metabolism are shown in the figure