Bacterial Species of Gut Microbiota are Identified to Be Associated with FOLFOX Treatment in Low-Set Rectal Cancer Patients

Background: FOLFOX treatment is a widely used method to reduce the tumor size of low-set rectal cancer with varied clinical results. The FOLFOX agents are a mixture of oxaliplatin and 5-fluorouracil, whose efficacy might be modulated by the gut microbiome in humans. This study is aimed to determine whether the bowel microbiota is a factor that influence the FOLFOX treatment. Methods: To investigate the role of gut microbiota during the FOLFOX treatment, we collected 62 fecal samples from low-set rectal cancer patients, and metagenomic sequencing was done for these fecal samples. Diverse bacterial taxa were identified by MetaGeneMark, Soapaligner and DIAMOND, and the microbiota data analyses were completed under R environment.   Findings: Differences in microbial taxa and MLGs were observed in multiple comparative analyses, and a group of 8 specific bacterial species are to be associated with the outcome of FOLFOX treatment. After the treatment, changes in bacteria diversity of microbiota were more apparent in the responder group than in the non-responder group. Experienced the treatment, the MLGs network construction was more complex in responder than in non-responder. Moreover, the enterotype shift in responders was consistency but the tendency in non-responders was difficult to find. Interpretation: The difference between responder and non-responder low-rectal cancer patients had appeared before therapy. There is a group of 8 specific bacterial species that can be used to stratify the gut microbiota of the patients, and possibly can be used for the prediction of FOLFOX treatment outcome. This finding suggests a forecast before FOLFOX to better prevent the harmful and poorly tolerated effects.    Funding: This study was partially supported by Beijing Municipal Natural Science Foundation (5174037), Major State Basic Research Development Program (2015CB554200), National High Technology Research and Development Program (2014AA020801) and China-Japan Friendship Hospital Research Funding (2016-1-MS-5). Declaration of Interest: None declared. Ethical Approval: This study was approved by local ethics committees (Institute of Microbiology, Chinese Academy of Sciences), and informed consent was obtained from all participants.