Skip to main content
Top
Published in: Gut Pathogens 1/2019

Open Access 01-12-2019 | Diarrhea | Research

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

Authors: Zuo Fei, Yin Lijuan, Yang Xi, Wu Wei, Zhong Jing, Da Miao, Han Shuwen

Published in: Gut Pathogens | Issue 1/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shuwen H, et al. Competitive endogenous RNA in colorectal cancer: a systematic review. Gene. 2018;645:157–62.CrossRef Shuwen H, et al. Competitive endogenous RNA in colorectal cancer: a systematic review. Gene. 2018;645:157–62.CrossRef
2.
go back to reference Rat C, et al. Effect of physician notification regarding nonadherence to colorectal cancer screening on patient participation in fecal immunochemical test cancer screening: a randomized clinical trial. JAMA. 2017;318(9):816–24.CrossRef Rat C, et al. Effect of physician notification regarding nonadherence to colorectal cancer screening on patient participation in fecal immunochemical test cancer screening: a randomized clinical trial. JAMA. 2017;318(9):816–24.CrossRef
3.
go back to reference Rossi L, et al. Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice. Future Oncol. 2012;8(9):1193–7.CrossRef Rossi L, et al. Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice. Future Oncol. 2012;8(9):1193–7.CrossRef
4.
go back to reference Zhou M, Fu L, Zhang J. Who will benefit more from maintenance therapy of metastatic colorectal cancer? Oncotarget. 2018;9(15):12479–86.CrossRef Zhou M, Fu L, Zhang J. Who will benefit more from maintenance therapy of metastatic colorectal cancer? Oncotarget. 2018;9(15):12479–86.CrossRef
5.
go back to reference Yoshida M, et al. A phase II study of third-line combination chemotherapy with bevacizumab plus S-1 for metastatic colorectal cancer with mutated KRAS (SAVIOR study). Oncology. 2016;91(1):24–30.CrossRef Yoshida M, et al. A phase II study of third-line combination chemotherapy with bevacizumab plus S-1 for metastatic colorectal cancer with mutated KRAS (SAVIOR study). Oncology. 2016;91(1):24–30.CrossRef
6.
go back to reference Hines RB, et al. Predictors of guideline treatment nonadherence and the impact on survival in patients with colorectal cancer. J Natl Compr Cancer Netw. 2015;13(1):51–60.CrossRef Hines RB, et al. Predictors of guideline treatment nonadherence and the impact on survival in patients with colorectal cancer. J Natl Compr Cancer Netw. 2015;13(1):51–60.CrossRef
7.
go back to reference Casadaban L, et al. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122(21):3277–87.CrossRef Casadaban L, et al. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122(21):3277–87.CrossRef
8.
go back to reference Booth CM, et al. Use and effectiveness of adjuvant chemotherapy for stage III colon cancer: a population-based study. J Natl Compr Canc Netw. 2016;14(1):47–56.CrossRef Booth CM, et al. Use and effectiveness of adjuvant chemotherapy for stage III colon cancer: a population-based study. J Natl Compr Canc Netw. 2016;14(1):47–56.CrossRef
9.
go back to reference Lee KJ. Pharmacologic agents for chronic diarrhea. Intest Res. 2015;13(4):306–12.CrossRef Lee KJ. Pharmacologic agents for chronic diarrhea. Intest Res. 2015;13(4):306–12.CrossRef
10.
go back to reference Andreyev J, et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol. 2014;15(10):e447–60.CrossRef Andreyev J, et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol. 2014;15(10):e447–60.CrossRef
11.
go back to reference Lee CS, Ryan EJ, Doherty GA. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol. 2014;20(14):3751–61.CrossRef Lee CS, Ryan EJ, Doherty GA. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol. 2014;20(14):3751–61.CrossRef
12.
go back to reference Han S, et al. Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review. Cancer Manag Res. 2018;10:199–206.CrossRef Han S, et al. Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review. Cancer Manag Res. 2018;10:199–206.CrossRef
13.
go back to reference Drewes JL, et al. High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia. NPJ Biofilms Microbiomes. 2017;3:34.CrossRef Drewes JL, et al. High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia. NPJ Biofilms Microbiomes. 2017;3:34.CrossRef
14.
go back to reference Tsai CE, et al. Associated factors in Streptococcus bovis bacteremia and colorectal cancer. Kaohsiung J Med Sci. 2016;32(4):196–200.CrossRef Tsai CE, et al. Associated factors in Streptococcus bovis bacteremia and colorectal cancer. Kaohsiung J Med Sci. 2016;32(4):196–200.CrossRef
15.
go back to reference Andres-Franch M, et al. Streptococcus gallolyticus infection in colorectal cancer and association with biological and clinical factors. PLoS ONE. 2017;12(3):e0174305.CrossRef Andres-Franch M, et al. Streptococcus gallolyticus infection in colorectal cancer and association with biological and clinical factors. PLoS ONE. 2017;12(3):e0174305.CrossRef
16.
go back to reference Castellarin M, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299–306.CrossRef Castellarin M, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299–306.CrossRef
17.
go back to reference Kostic AD, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207–15.CrossRef Kostic AD, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207–15.CrossRef
18.
go back to reference Kumar M, et al. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev. 2013;71(1):23–34.CrossRef Kumar M, et al. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev. 2013;71(1):23–34.CrossRef
19.
go back to reference Oke S, Martin A. Insights into the role of the intestinal microbiota in colon cancer. Ther Adv Gastroenterol. 2017;10(5):417–28.CrossRef Oke S, Martin A. Insights into the role of the intestinal microbiota in colon cancer. Ther Adv Gastroenterol. 2017;10(5):417–28.CrossRef
20.
go back to reference Youmans BP, et al. Characterization of the human gut microbiome during travelers’ diarrhea. Gut Microbes. 2015;6(2):110–9.CrossRef Youmans BP, et al. Characterization of the human gut microbiome during travelers’ diarrhea. Gut Microbes. 2015;6(2):110–9.CrossRef
21.
go back to reference Mulatu G, Beyene G, Zeynudin A. Prevalence of Shigella, Salmonella and Campylobacter species and their susceptibility patters among under five children with diarrhea in Hawassa town, south Ethiopia. Ethiop J Health Sci. 2014;24(2):101–8.CrossRef Mulatu G, Beyene G, Zeynudin A. Prevalence of Shigella, Salmonella and Campylobacter species and their susceptibility patters among under five children with diarrhea in Hawassa town, south Ethiopia. Ethiop J Health Sci. 2014;24(2):101–8.CrossRef
22.
go back to reference Zhang X, et al. Presence and characterization of Klebsiella pneumoniae from the intestinal tract of diarrhoea patients. Lett Appl Microbiol. 2018;66(6):514–22.CrossRef Zhang X, et al. Presence and characterization of Klebsiella pneumoniae from the intestinal tract of diarrhoea patients. Lett Appl Microbiol. 2018;66(6):514–22.CrossRef
24.
go back to reference Amisano G, Fornasero S, Migliaretti G, Caramello S, Tarasco V, Savino F. Diarrheagenic Escherichia coli in acute gastroenteritis in infants in North-West Italy. New Microbiol. 2011;34(1):45–51.PubMed Amisano G, Fornasero S, Migliaretti G, Caramello S, Tarasco V, Savino F. Diarrheagenic Escherichia coli in acute gastroenteritis in infants in North-West Italy. New Microbiol. 2011;34(1):45–51.PubMed
26.
go back to reference Keefe DM, et al. Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with colorectal cancer receiving multi-cycle chemotherapy. Cancer Chemother Pharmacol. 2014;74(4):675–80.CrossRef Keefe DM, et al. Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with colorectal cancer receiving multi-cycle chemotherapy. Cancer Chemother Pharmacol. 2014;74(4):675–80.CrossRef
27.
go back to reference Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.PubMed Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.PubMed
28.
go back to reference Issa I, Moucari R. Probiotics for antibiotic-associated diarrhea: do we have a verdict? World J Gastroenterol. 2014;20(47):17788–95.CrossRef Issa I, Moucari R. Probiotics for antibiotic-associated diarrhea: do we have a verdict? World J Gastroenterol. 2014;20(47):17788–95.CrossRef
29.
go back to reference Hari DM, et al. AJCC cancer staging manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217(2):181–90.CrossRef Hari DM, et al. AJCC cancer staging manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217(2):181–90.CrossRef
30.
go back to reference Trotti A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176–81.CrossRef Trotti A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176–81.CrossRef
31.
go back to reference Quast C, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucl Acids Res. 2013;41(D1):D590–6.CrossRef Quast C, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucl Acids Res. 2013;41(D1):D590–6.CrossRef
32.
go back to reference Fish JA, et al. FunGene: the functional gene pipeline and repository. Front Microbiol. 2013;4:291.CrossRef Fish JA, et al. FunGene: the functional gene pipeline and repository. Front Microbiol. 2013;4:291.CrossRef
33.
go back to reference Schloss PD, et al. Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-based studies. PLoS ONE. 2011;6(12):e27310.CrossRef Schloss PD, et al. Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-based studies. PLoS ONE. 2011;6(12):e27310.CrossRef
34.
go back to reference Segata N, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.CrossRef Segata N, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.CrossRef
35.
go back to reference Andre T, et al. The IDEA (international duration evaluation of adjuvant chemotherapy) collaboration: prospective combined analysis of phase III trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or modified FOLFOX6) or XELOX (3 versus 6 months) regimen for patients with stage III colon cancer: trial design and current status. Curr Colorectal Cancer Rep. 2013;9:261–9.CrossRef Andre T, et al. The IDEA (international duration evaluation of adjuvant chemotherapy) collaboration: prospective combined analysis of phase III trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or modified FOLFOX6) or XELOX (3 versus 6 months) regimen for patients with stage III colon cancer: trial design and current status. Curr Colorectal Cancer Rep. 2013;9:261–9.CrossRef
36.
go back to reference Benson AR, et al. NCCN guidelines insights: colon cancer, version 2.2018. J Natl Compr Cancer Netw. 2018;16(4):359–69.CrossRef Benson AR, et al. NCCN guidelines insights: colon cancer, version 2.2018. J Natl Compr Cancer Netw. 2018;16(4):359–69.CrossRef
37.
go back to reference Brady J, et al. An open-label study of the safety and tolerability of pazopanib in combination with FOLFOX6 or CapeOx in patients with colorectal cancer. Invest New Drugs. 2013;31(5):1228–35.CrossRef Brady J, et al. An open-label study of the safety and tolerability of pazopanib in combination with FOLFOX6 or CapeOx in patients with colorectal cancer. Invest New Drugs. 2013;31(5):1228–35.CrossRef
38.
go back to reference Hoff PM, et al. Randomized phase III trial exploring the use of long-acting release octreotide in the prevention of chemotherapy-induced diarrhea in patients with colorectal cancer: the LARCID trial. J Clin Oncol. 2014;32(10):1006–11.CrossRef Hoff PM, et al. Randomized phase III trial exploring the use of long-acting release octreotide in the prevention of chemotherapy-induced diarrhea in patients with colorectal cancer: the LARCID trial. J Clin Oncol. 2014;32(10):1006–11.CrossRef
39.
go back to reference Carroll IM, et al. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6): 521–30, e248. Carroll IM, et al. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6): 521–30, e248.
40.
go back to reference Lee JR, et al. Gut microbial community structure and complications after kidney transplantation: a pilot study. Transplantation. 2014;98(7):697–705.CrossRef Lee JR, et al. Gut microbial community structure and complications after kidney transplantation: a pilot study. Transplantation. 2014;98(7):697–705.CrossRef
41.
go back to reference Guard BC, et al. Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea. PLoS ONE. 2015;10(5):e0127259.CrossRef Guard BC, et al. Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea. PLoS ONE. 2015;10(5):e0127259.CrossRef
42.
go back to reference Lu B, et al. Molecular characterization of Klebsiella pneumoniae isolates from stool specimens of outpatients in sentinel hospitals Beijing, China, 2010-2015. Gut Pathog. 2017;9:39.CrossRef Lu B, et al. Molecular characterization of Klebsiella pneumoniae isolates from stool specimens of outpatients in sentinel hospitals Beijing, China, 2010-2015. Gut Pathog. 2017;9:39.CrossRef
Metadata
Title
Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer
Authors
Zuo Fei
Yin Lijuan
Yang Xi
Wu Wei
Zhong Jing
Da Miao
Han Shuwen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2019
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-019-0299-4

Other articles of this Issue 1/2019

Gut Pathogens 1/2019 Go to the issue