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Supportive Care in Cancer
Published in: Supportive Care in Cancer 7/2013

01-07-2013 | Original Article

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

Authors: Andrea M. Stringer, Noor Al-Dasooqi, Joanne M. Bowen, Thean H. Tan, Maryam Radzuan, Richard M. Logan, Bronwen Mayo, Dorothy M. K. Keefe, Rachel J. Gibson

Published in: Supportive Care in Cancer | Issue 7/2013

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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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Metadata
Title
Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases
Authors
Andrea M. Stringer
Noor Al-Dasooqi
Joanne M. Bowen
Thean H. Tan
Maryam Radzuan
Richard M. Logan
Bronwen Mayo
Dorothy M. K. Keefe
Rachel J. Gibson
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Supportive Care in Cancer / Issue 7/2013
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-013-1741-7

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