Gut microbiome components predict response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients: a prospective, longitudinal study.

Purpose The gut microbiome (GM) is involved into anti-tumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of GM in predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) remains scarce. This prospective, longitudinal study aims to evaluate the feasibility of the GM in predicting nCRT responses. Experimental design We collected 167 fecal samples from 84 LARC patients before and after nCRT and 31 specimens from healthy individuals for 16S rRNA sequencing. Patients were divided into responders and non-responders according to pathological response to nCRT. After identifying microbial biomarkers related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training cohort of baseline samples from 37 patients and validated the classifier in another cohort of 47 patients. Results We observed significant microbiome alterations represented by a decrease in LARC-related pathogens and an increase in Lactobacillus and Streptococcus during nCRT. Furthermore, a prominent microbiota difference between responders and non-responders was noticed in the baseline samples. Microbes related with butyrate production including Roseburia, Dorea and Anaerostipes, were overrepresented in responders, whereas Coriobacteriaceae and Fusobacterium were overrepresented in non-responders. Ten biomarkers were selected for the response-prediction classifier, including Dorea, Anaerostipes and Streptococcus, which yielded an area under the curve value of 93.57% (95% CI: 85.76%-100.00%) in the training cohort and 73.53% (95% CI: 58.96%-88.11%) in the validation cohort. Conclusions The GM offers novel potential biomarkers for predicting nCRT responses, which has important manifestations in the clinical management of these patients.