# Microbiota Modulation of Radiosensitiveness and Toxicity in Gastrointestinal Cancers: What Radiation Oncologists Need to Know—A Review on Behalf of the Italian Association of Radiobiology (AIRB)

## TL;DR

This review explores how gut microbiota can influence the effectiveness and side effects of radiation therapy in gastrointestinal cancers, highlighting the potential for microbiota modulation to improve treatment outcomes.

## Contribution

The paper provides a comprehensive review of preclinical and clinical evidence on microbiota's role in modulating radiotherapy outcomes in gastrointestinal cancers.

## Key findings

- Prebiotics and probiotics show promise in mitigating radiotherapy-induced toxicity in rectal cancer.
- Microbiota modulation may impact treatment toxicity and efficacy in esophageal cancer, HCC, and ASCC.
- More research is needed to support the clinical use of microbiota modulation for enhancing tumor radiosensitivity.

## Abstract

The impact of the microbiota on radiation (RT)-induced toxicity and cancer response to radiotherapy is an emerging area of interest. In this review, we summarize the available preclinical and clinical evidence concerning microbiota modulation of RT toxicity and efficacy in the main gastrointestinal (GI) districts. A huge amount of data supports the clinical application of microbiota modulation, particularly through prebiotics and probiotics, to prevent or mitigate radiotherapy-induced toxicity in rectal cancer. Preclinical and clinical studies also support the observation of microbiota modulation to impact the toxicity and efficacy of treatment in esophageal cancer, hepatocellular carcinoma (HCC), and anal squamous cell carcinoma (ASCC). However, insufficient evidence remains to endorse microbiota modulation as a strategy to enhance tumor radiosensitivity in clinical practice. Well-designed studies focusing on prebiotics, probiotics, and fecal microbiota transplantation are needed across all GI sites to evaluate their potential to improve treatment efficacy, as suggested by promising preclinical findings. The impact of pre-treatment microbiota analyses should be addressed in prospective studies to verify the efficacy of patient-level tailored strategies. Additionally, the repurposing of radioprotective agents with innovative delivery systems, such as encapsulated amifostine, holds significant promise for mitigating small bowel toxicity, thereby enabling more effective RT treatment.