期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms22179549
关键词
colorectal cancer; gut microbiota; SCFAs; gut permeability; radiochemotherapy; treatment outcome
资金
- Institute of Health Carlos III (ISCIII) [PI15/00256]
- Fondo Europeo de Desarrollo Regional-FEDER
- Miguel Servet Type II program (ISCIII, Spain) [CPI18/00003]
- Nicolas Monardes research program of the Consejeria de Salud (Junta de Andalucia, Spain) [C-0030-2018]
- Miguel Servet Type I program (ISCIII, Spain) [CP19/00098]
- Consejeria de Salud y Familia [PE-0106-2019]
- Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain
- PFIS-ISCIII [FI19-00112]
- Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain
This study suggests that gut microbiota composition plays a role in the response to cancer therapies in CRC patients. Responders had higher microbial diversity and abundance of butyrate-producing bacteria, as well as higher levels of specific metabolites, while non-responders exhibited a microbiota rich in pro-inflammatory species.Ultimately, a baseline consortium of five bacterial species was identified as potential predictors of CRC treatment outcome.
Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.
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