A pilot study of gut mucosal and faecal microbiota in rectal cancer: associations with histological response and adverse events following preoperative chemoradiotherapy

Abstract

Aim: Preoperative chemoradiotherapy (CRT) is administered for locally advanced rectal cancer (LARC); however, its efficacy and toxicity vary among patients. This study aimed to elucidate the relationship between the gut microbiota and the effectiveness and adverse events of CRT.

Methods: This prospective study included 21 patients with LARC with no history of antibiotic or probiotic administration for 6 months. Tumour mucosa, non-tumour mucosa and faecal samples were collected before and after CRT, and bacterial DNA was extracted. Metataxonomic analysis targeting the V3 and V4 regions of the 16S rRNA gene was conducted to determine the diversity and composition of the microbiota. Linear discriminant analysis effect size (LEfSe) was used to explore potential bacterial taxa predicting pathological complete response (pCR) and treatment-associated diarrhoea, which are major adverse events of CRT.

Results: Among the 21 patients, five achieved pCR and seven experienced severe treatment-associated diarrhoea. There were no significant differences in α-diversity and β-diversity of the microbiota between the groups at any sampling sites before or after CRT. Exploratory analysis using LEfSe identified Peptostreptococcus, Coprococcus and Phoceaicola in the tumour mucosa before CRT as significant indicators for achieving pCR. Additionally, Collinsella, Haemophilus and Desulfovibrionaceae are associated with treatment-associated diarrhoea. Microbiome composition changed before and after CRT, with a notable decrease in the genus Fusobacterium_C and other taxa. β-diversity in the tumour area also changed significantly (P = 0.03).

Conclusions: This study suggests an association between the gut microbiota, the therapeutic effectiveness of CRT and the occurrence of treatment-associated diarrhoea in rectal cancer. These results indicate the potential for predicting treatment efficacy and adverse events based on the microbiota composition.

Keywords: chemoradiotherapy; microbiota; mucosal microbiome; pathological complete response; rectal cancer; treatment‐associated diarrhoea.