Baseline rectal mucosal microbiota and response to neoadjuvant chemoradiotherapy: a pilot cohort study
David Julià-Bergkvist, Sandra Taboada-Lopez, Nuria Gomez-Romeu, Marta Malagon, Lia Oliver, Mariona Serra-Pages, Ander Timoteo, Olga Delisau, Eloi Maldonado, Anna Pigem, Maria Gomez-Jurado, Judith Luquin, Paula Creus, Frank Fernandez, David Sambrano, Marc Fonollosa, Bernat Montane, Laia Coll, Pere Planellas, Xavier Aldeguer, Ramon FarresAbstract
Introduction
The gut microbiota may influence response to neoadjuvant chemoradiotherapy in rectal cancer, but whether baseline rectal mucosal microbiota is associated with treatment response remains uncertain.
Methods
This prospective observational cohort included 17 patients with locally advanced rectal cancer treated with long-course nCRT followed by surgery. Pretreatment rectal mucosal biopsies were obtained during staging endoscopic ultrasonography. Microbial DNA underwent V3–V4 16S rRNA sequencing on Illumina MiSeq. Reads were processed with QIIME2/DADA2 and taxonomy assigned using SILVA 138. Response was assessed separately by Mandard tumour regression grade (TRG) and downstaging. Alpha diversity, beta diversity, and taxonomic composition were compared between responders and non-responders.
Results
Median age was 73 years and 76.5% were male. TRG1–2 was observed in 6/17 patients (35.3%), while downstaging occurred in 10/17 (58.8%). Baseline mucosal microbiota showed no significant differences in alpha diversity, beta diversity, or taxonomic composition between responders and non-responders according to either response definition. Bacillota, Bacteroidota, and Proteobacteria predominated in all groups. Dispersion analyses showed greater inter-individual microbial heterogeneity in non-responders according to Mandard TRG, whereas responders defined by downstaging showed greater dispersion.
Discussion
Baseline rectal mucosal microbiota was not associated with a consistent microbial signature of response to nCRT in this pilot cohort. Microbial heterogeneity differed according to the response metric used, suggesting that any microbiota-response relationship may be complex and not captured by a single baseline profile. These findings are exploratory and require validation in larger cohorts.