The gut microbiota as a booster for radiotherapy: novel insights into radio-protection and radiation injury

Abstract

Approximately 60–80% of cancer patients treated with abdominopelvic radiotherapy suffer post-radiotherapy toxicities including radiation enteropathy and myelosuppression. Effective preventive and therapeutic strategies are lacking for such radiation injury. The gut microbiota holds high investigational value for deepening our understanding of the pathogenesis of radiation injury, especially radiation enteropathy which resembles inflammatory bowel disease pathophysiology and for facilitating personalized medicine by providing safer therapies tailored for cancer patients. Preclinical and clinical data consistently support that gut microbiota components including lactate-producers, SCFA-producers, indole compound-producers and Akkermansia impose intestinal and hematopoietic radio-protection. These features serve as potential predictive biomarkers for radiation injury, together with the microbial diversity which robustly predicts milder post-radiotherapy toxicities in multiple types of cancer. The accordingly developed manipulation strategies including selective microbiota transplantation, probiotics, purified functional metabolites and ligands to microbe-host interactive pathways are promising radio-protectors and radio-mitigators that merit extensive validation in clinical trials. With massive mechanistic investigations and pilot clinical trials reinforcing its translational value the gut microbiota may boost the prediction, prevention and mitigation of radiation injury. In this review, we summarize the state-of-the-art landmark researches related with radio-protection to provide illuminating insights for oncologists, gastroenterologists and laboratory scientists interested in this overlooked complexed disorder.

Heterogeneity in precision oncology

“…The microbiome studies shape oncologic outcomes and are now being leveraged for the development of novel personalised therapeutic approaches in anticancer treatment. However, this topic exceeds the scope of this paper and has been addressed elsewhere (Chrysostomou et al, 2023 ; Yi et al, 2023 ).…”

Urine microbiome changes during and after radiotherapy for prostate cancer

“…Conversely, a disrupted microbiota has the potential to diminish the effectiveness of radiotherapy (10) . Most of these observations were made concerning the gut microflora, which directly affects the functioning of the immune system (36,37) . Matson et al, based on studies conducted on mice, observed that gut microflora can also migrate to other closely related tissues and influence cancer progression (38) .…”

Effects of combined ciprofloxacin and Neulasta therapy on intestinal pathology and gut microbiota after high-dose irradiation in mice

“…This bacterium is commercially available as a probiotic, but its increase in abundance in trauma patients who have died suggests a potential negative effect ( 51 ). Similarly, there are mixed reports on the role that A. muciniphila plays following radiation ( 23 , 42 , 50 , 52 , 53 ). Tian et al ( 52 ) used an oral gavage of Akkermansia to demonstrate increases in mouse survival over a 30-day period following irradiation with enhanced production of SCFAs.…”

“…Tian et al ( 52 ) used an oral gavage of Akkermansia to demonstrate increases in mouse survival over a 30-day period following irradiation with enhanced production of SCFAs. Conversely, Akkermansia has been associated with inflammation as it is consistently found as an organism more abundant following irradiation and in colitis models ( 42 , 50 , 52 – 54 ). Gerassy-Vainberg et al ( 50 ) demonstrated that radiation induces a proinflammatory state with increased Akkermansia .…”