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Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases

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Abstract

Purpose

A common side effect of chemotherapy treatment is diarrhoea. Unfortunately, the underlying mechanisms of chemotherapy-induced diarrhoea (CD) are poorly understood. We aimed to determine if faecal microbes of CD patients were displaced, if faecal calprotectin increased during CD and if there were alterations in circulating matrix metalloproteinases, nuclear factor kappa B (NF-κB), IL-1β and TNF.

Patients and methods

Twenty-six cancer patients receiving chemotherapy were enrolled and requested to provide stool samples and blood samples at various times during their chemotherapy cycle. Stool samples were analysed using conventional culture techniques and qRT-PCR. ELISA kits determined faecal calprotectin levels, levels of circulating matrix metalloproteinases and circulating NF-κB, IL-1β and TNF.

Results

The majority of patients with CD showed decreases in Lactobacillus spp., Bifidobacterium spp., Bacteroides spp. and Enterococcus spp. Increases were observed in Escherichia coli and Staphylococcus spp. Methanogenic archaea were also quantified, with all patients except one showing a decrease. Faecal calprotectin levels were increased in 81.25 % of patients with CD. Circulating MMP-3 and MMP-9 significantly increased following chemotherapy. Circulating levels of NF-κB, IL-1β and TNF were increased following chemotherapy, although this did not reach significance.

Conclusions

We demonstrated that CD is associated with marked changes in intestinal microflora, methanogenic archaea, matrix metalloproteinase and serum levels of NF-κB, IL-1β and TNF. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. More importantly, these changes may provide clinicians with a possible new target for biomarkers of toxicity.

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Acknowledgments

Funding for this project was provided by a Cure Cancer/Cancer Australia Research Grant awarded to Dr Rachel Gibson; Dr Andrea Stringer is the recipient of an NHMRC Post-Doctoral Training Fellowship; Dr Noor Al-Dasooqi is the recipient of a Clinical Centre of Research Excellence Post-Doctoral Fellowship; Dr Joanne Bowen is the recipient of an NHMRC Post-Doctoral Training Fellowship; and Professor Dorothy Keefe is the Professor of Cancer Medicine.

Conflict of interest

None of the authors listed on this manuscript have any financial relationship with the funding bodies that provided money for this research. Further, all authors have full control of all primary data and we consent to allowing the journal to review any/all data if requested.

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Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    Andrea M. Stringer & Maryam Radzuan

  2. Discipline of Medicine, University of Adelaide, Adelaide, Australia

    Andrea M. Stringer, Noor Al-Dasooqi, Bronwen Mayo & Dorothy M. K. Keefe

  3. School of Medical Sciences, University of Adelaide, North Terrace, Adelaide, 5005, South Australia, Australia

    Andrea M. Stringer, Noor Al-Dasooqi, Joanne M. Bowen & Rachel J. Gibson

  4. Cancer Centre, Royal Adelaide Hospital, Adelaide, South Australia, Australia

    Thean H. Tan & Dorothy M. K. Keefe

  5. Oral Pathology, School of Dentistry, University of Adelaide, Adelaide, Australia

    Richard M. Logan

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  1. Andrea M. Stringer
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Correspondence to Rachel J. Gibson.

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Stringer, A.M., Al-Dasooqi, N., Bowen, J.M. et al. Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases. Support Care Cancer 21, 1843–1852 (2013). https://doi.org/10.1007/s00520-013-1741-7

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  • DOI: https://doi.org/10.1007/s00520-013-1741-7

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