Gut Microbiome Composition Is Associated with a Pathologic Response After Preoperative Chemoradiation in Patients with Rectal Cancer

The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study

“…Several bacteria taxa with significantly different abundances between responders and non-responders were identified ( Figures 3A, B and Table 4), although no significant differences in the richness/diversity in bacterial microbiome as well as microbial profile were noted ( Supplementary Figures 2 and 3). Our finding that member of the Bacteroidales order including Parabacteroides merdae is enriched in non-responders, was consistent with the enrichment of Bacteroidales order in non-responders of melanoma patients who received anti-PD-1 immunotherapy (Gopalakrishnan and Spencer, 2018) and the enrichment in non-responders of rectal cancer patients who received preoperative concurrent chemoradiation (Jang, 2020). It is unexpected and needs further validation that Faecalibacterium/ Prausnitzii was identified as enriched in non-responders compared to responders (Figure 3) and also enriched in non-responders before nCRT compared to after nCRT (Supplementary Figure 5), since Faecalibacterium/Prausnitzii was suggested to be positively correlated with CD8+ T cell infiltrate in the tumor and favorable responses to anti-PD-1 immunotherapy (Gopalakrishnan and Spencer, 2018).…”

“…By modulating microbiome, the therapeutic responses may be improved (Iida et al, 2013;Sivan et al, 2015;Routy and Le Chatelier, 2018;Matson et al, 2018;Gopalakrishnan and Spencer, 2018) and toxicities may be alleviated (Delia et al, 2002;Delia et al, 2007;Wallace et al, 2010). However, so far, no studies have systematically analyzed the correlation between the gut microbiome and therapeutic responses or toxicities of nCRT in rectal cancer patients (Manichanh et al, 2008;Nam et al, 2013;Wang et al, 2015), except for one fairly recent study, which demonstrated the correlation between pathologic response after preoperative concurrent chemoradiation and gut microbiome composition in rectal cancer patients (Jang, 2020). In addition to the correlation with therapeutic responses, the current study analyzed the correlation of gut microbiome with toxicities of nCRT in rectal cancer patients, which identified the potential microbiota and pathway markers to predict therapeutic responses and toxicities of nCRT in patients with rectal cancer and suggested the possibility to improve therapeutic responses and alleviate toxicities by manipulating microbiome.…”

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

“…54 A second study analyzing fecal composition prior to preoperative concurrent chemoradiations in 45 rectal cancer patients concluded that Duodenibacillus massiliensis was linked to complete responses. 55 Altogether, the emerging field of oncoimmunomicrobiology is progressively integrating the gut microbiota into the parameters that determine the cancer immune set-point governing the clinical efficacy of immuno-chemo-radio-therapy. First, low alpha diversity of the intestinal ecosystem is associated with dismal prognosis in advanced cancer patients, as also shown in several chronic inflammatory disorders (such as obesity).…”

“…although variabilities in the main commensal fingerprints associated with a specific pattern of responses appear obvious within analogous patients' populations and therapies. These variabilities could be explained by many factors such as DNA extraction and sequencing methodologies, 55 cohort size, age and gender, geography, 57,58 and confounding factors (including diet, lifestyle, exposure to xenobiotics, antibiotic class and window, comedications and comorbidities). 59,60 Other important players that affect intestinal barrier integrity are the tumor itself, disease stage, ECOG performance status, medication, peripheral inflammatory tone, and pro-cachexia signs.…”

“… 54 A second study analyzing fecal composition prior to preoperative concurrent chemoradiations in 45 rectal cancer patients concluded that Duodenibacillus massiliensis was linked to complete responses. 55 …”