Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study

Abstract

Purpose: The gut microbiome is involved in antitumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of gut microbiome in predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) remains scarce. This prospective, longitudinal study aimed to evaluate the feasibility of the gut microbiome in predicting nCRT responses. Experimental Design: We collected 167 fecal samples from 84 patients with LARC before and after nCRT and 31 specimens from healthy individuals for 16S rRNA sequencing. Patients were divided into responders and nonresponders according to pathologic 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 nonresponders 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 nonresponders. 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% confidence interval (CI), 85.76%–100%] in the training cohort and 73.53% (95% CI, 58.96%–88.11%) in the validation cohort. Conclusions: The gut microbiome offers novel potential biomarkers for predicting nCRT responses, which has important manifestations in the clinical management of these patients.

Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases

“…Bacteria of the Dorea sp. genus, one of the most common species of the gut microbiota, are increased in conditions of deficiency of Se ( 101) and are associated with IBS, cancer, multiple sclerosis, and non-alcoholic liver disease (101,(127)(128)(129)(130). Se deficiency and inadequate selenoprotein expression impairs innate and adaptive immune responses with higher levels of inflammatory cytokines, especially at colonic level.…”

Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer

“…Clinical evidence-based research on the role of potential gut microbial biomarkers for predicting patient’s response to chemotherapy is scarce. In 2020, two Asian cohort studies [ 85 , 86 ] aimed to evaluate the predictive value of the gut microbiome in terms of the response after preoperative concurrent chemoradiation (nCCRT) in patients with rectal cancer. Jang et al [ 85 ], after analyzing 45 fecal samples, showed that Bacteroidales (Bacteroidaceae, Rikenellaceae, Bacteroides ) were relatively more abundant in patients with a noncomplete response than in those with complete response.…”

“…Additionally, the authors found that Duodenibacillus massiliensis was associated with a complete response. Yi et al [ 86 ] identified potential microbial biomarkers for predicting the response to nCCRT in locally advanced rectal cancer: butyrate-producing bacteria, including Roseburia , Dorea , and Anaerostipes were overrepresented in responders, whereas Coriobacteriaceae and Fusobacterium were markedly higher in non-responders. Although gut dysbiosis could be a relevant biomarker to predict radiotherapy-induced mucositis [ 87 , 88 ], the direct impact on the patients’ response to radiotherapy has not yet been investigated yet.…”

Correlation of Gut Microbiota with Efficacy of Chemotherapy in Patients with Diffuse Large B-cell Lymphoma

“…Lactobacillus fermentum became the dominant microbiota in complete remission patient, which was related to the changes in lymphoid tumor and resulted from the gut microbiota succession caused by chemotherapy intervention and tumor extinction. Recent studies have indicated that signi cant microbiome alterations represented an increase in Lactobacillus during nCRT (neoadjuvant chemoradiotherapy) [22] . Therefore, the product of Lactobacillus fermentum may directly involve in antitumor,synergistically with chemoradiotherapy, and enhance the therapeutic effect of chemotherapeutic drugs.…”