Relationship between Gut Commensal Bacteria and Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Abstract Gut commensal bacteria may have a potential in distorting the response of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (nCRT). To this end, fecal samples of 35 LARC patients were retrospectively collected during nCRT in our center. According to pathological tumor regression grade (TRG) classification system (AJCC 8.0), recruited patients were divided into Sensitive group (TRG 0 ~ 1, n = 12) and Resistant group (TRG 2 ~ 3, n = 23) after radical surgery. Fecal bacterial structures of two groups were compared after bacterial 16S rRNA sequencing. In this study, it was found that fecal bacterial structures of two groups before nCRT were significantly different, presenting a higher abundance of butyrate-producing bacteria in feces of Sensitive group, whereas a higher abundance of colorectal cancer-facilitated bacteria in feces of Resistant group. During nCRT, β-diversities of two groups were significantly decreased comparing to their baseline, but bacterial structures of two groups were remodeled differentially, presenting that unlike in Sensitive group, the bacterial structure in Resistant group was continuously evolved as nCRT-dose increased. Intriguingly, it was found that the abundance of Akkermansia.muciniphila, a critical member of probiotics, was positively correlated with tumorigenic bacteria in feces of LARC patients resistant to nCRT, but the bacterial function network analysis revealed that Akkermansia.muciniphila counteracted against tumorigenic bacteria, such as Escherichia and Bacteroides. This highlighted a potential of Akkermansia.muciniphila in improving LARC response to nCRT. Collectively, gut bacterial structure impacts the response of LARC to nCRT. In turn, nCRT will remodel gut bacterial structures among LARC patients, thus enabling their treatment responses to be inconsistent.