The Effect of a Multi-Species Probiotic Formulation to Prevent Chemotherapy-induced Diarrhoea by Rescuing Gastrointestinal Dysbiosis and Mucositis. A Feasibility Probing Study
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Open Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Thomsen, MichaelAbstract
The gut microbiome has been shown to influence the efficacy and tolerance of cancer treatments. Mucositis is a dose-limiting side-effect of treatment, with adverse effects on nutritional intake. The objective of this thesis was to assess the therapeutic efficacy of a probiotic ...
See moreThe gut microbiome has been shown to influence the efficacy and tolerance of cancer treatments. Mucositis is a dose-limiting side-effect of treatment, with adverse effects on nutritional intake. The objective of this thesis was to assess the therapeutic efficacy of a probiotic formulation in preventing and improving gut mucositis/dysbiosis. Methods: The effect of cancer treatments on quality of life (QoL) was assessed using the FACT-C questionnaire that included patient well-being and gut adverse symptoms (e.g., diarrhoea). Bacterial DNA was extracted from faecal samples, sequenced, and taxonomically examined. Participants rated faecal samples via the Bristol Stool Chart. Assessment of incidence/severity of neutropenia via white blood cell and neutrophil counts, circulating short chain fatty acids (SCFAs) levels assayed via gas chromatography with mass spectrometry (GC-MS), and plasma lipopolysaccharide (LPS) via the limulus amoebocyte lysate chromogenic endotoxin quantification kit were recorded. Results: No significant changes in QoL scores observed. Improvement in bowel function, with reduction in constipation or diarrhoea or absence of significant disturbance to bowel function was observed in 85% of participants. One participant developed febrile neutropenia and two developed bowel toxicity during the study, unrelated to the probiotic. No significant changes in microbiome diversity from baseline to end of study were observed. None of the participants had raised plasma LPS or SCFAs. Probiotics were deemed overall as safe and tolerable. In a related observational study of exceptional responders to chemotherapy, participants were found to have had a high intake of fruits, vegetables, and fibre. Conclusion: A healthy microbiome is associated with reduced adverse events and increased tolerability to cancer treatments. Enhanced gut health may also improve QoL during treatment. High fibre intake is likely to increase gut microbiome abundance and diversity, contributing capacity to tolerate chronic chemotherapy, improving long-term survival. In this study probiotics may have alleviated diarrhoea, constipation and maintain stool consistency/frequency during cancer treatments. Limitations of a single group study design make it difficult to ascribe definitive conclusions. Future studies warrant larger sample sizes, control groups and limit recruitment to a homogenous group of patients.
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See moreThe gut microbiome has been shown to influence the efficacy and tolerance of cancer treatments. Mucositis is a dose-limiting side-effect of treatment, with adverse effects on nutritional intake. The objective of this thesis was to assess the therapeutic efficacy of a probiotic formulation in preventing and improving gut mucositis/dysbiosis. Methods: The effect of cancer treatments on quality of life (QoL) was assessed using the FACT-C questionnaire that included patient well-being and gut adverse symptoms (e.g., diarrhoea). Bacterial DNA was extracted from faecal samples, sequenced, and taxonomically examined. Participants rated faecal samples via the Bristol Stool Chart. Assessment of incidence/severity of neutropenia via white blood cell and neutrophil counts, circulating short chain fatty acids (SCFAs) levels assayed via gas chromatography with mass spectrometry (GC-MS), and plasma lipopolysaccharide (LPS) via the limulus amoebocyte lysate chromogenic endotoxin quantification kit were recorded. Results: No significant changes in QoL scores observed. Improvement in bowel function, with reduction in constipation or diarrhoea or absence of significant disturbance to bowel function was observed in 85% of participants. One participant developed febrile neutropenia and two developed bowel toxicity during the study, unrelated to the probiotic. No significant changes in microbiome diversity from baseline to end of study were observed. None of the participants had raised plasma LPS or SCFAs. Probiotics were deemed overall as safe and tolerable. In a related observational study of exceptional responders to chemotherapy, participants were found to have had a high intake of fruits, vegetables, and fibre. Conclusion: A healthy microbiome is associated with reduced adverse events and increased tolerability to cancer treatments. Enhanced gut health may also improve QoL during treatment. High fibre intake is likely to increase gut microbiome abundance and diversity, contributing capacity to tolerate chronic chemotherapy, improving long-term survival. In this study probiotics may have alleviated diarrhoea, constipation and maintain stool consistency/frequency during cancer treatments. Limitations of a single group study design make it difficult to ascribe definitive conclusions. Future studies warrant larger sample sizes, control groups and limit recruitment to a homogenous group of patients.
See less
Date
2022Rights statement
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Faculty of Medicine and Health, School of Medical SciencesDepartment, Discipline or Centre
Department of Medical SciencesAwarding institution
The University of SydneyShare