Introduction
There is currently an urgent and unmet need to determine an individual’s risk of developing gastrointestinal toxicity prior to chemotherapy. The microbiome has received attention for its role in regulating an individual’s risk of gastrointestinal toxicity due to its ability to modulate the host’s immune system and metabolise some chemotherapy agents. As such, pre-treatment microbial profiling presents as a novel risk stratification method. This study aimed to characterize pre-treatment microbial profiles in patients undergoing chemotherapy for breast and colorectal cancer.
Methods
Patients with breast and colorectal cancer were recruited from the Royal Adelaide Hospital in South Australia. Stool samples were collected from patients before their chemotherapy treatment began (T0) and at day 5 (T5). Clinical case notes were used to determine clinical toxicity score and diarrhea severity. Toxic patients were defined as >Grade 1 diarrhoea (NCI CTCAE v.4 guidelines). Microbial composition was assessed by 16S rRNA sequencing and bioinformatics analyses.
Results
Twelve patients undergoing a 5-fluorouracil based chemotherapy regimen (mean age= 62.25 years) were recruited. Five of these patients were defined as toxic. No significant changes were identified in the microbiota composition following chemotherapy, including species diversity measures (T0 vs T5; p=0.058). Pre-treatment microbial analysis, at the genus level, revealed significantly higher Blautia abundance in non-toxic patients compared to those that developed diarrhoea (p=0.003).
Conclusions
This pilot study is an important step in determining whether the gut microbiome can be used as a diagnostic marker in determining risk of severe CIGT. These results suggest that the genus Blautia may be critical in determining an individual patient’s likelihood of developing diarrhoea following chemotherapy. Further research is required to validate this in a larger cohort of participants.