Gut microbiota may influence radiotherapy response and intestinal side effects

Radiotherapy is an important treatment for many cancers, using ionizing radiation to damage tumor cells and control disease progression. However, it can also affect surrounding healthy tissues, and gastrointestinal toxicity remains a major challenge for patients receiving abdominal or pelvic radiotherapy. Radiation enteritis, characterized by symptoms such as diarrhea, abdominal discomfort, and intestinal inflammation, may affect quality of life and treatment tolerance.

In a review published in Journal of Holistic Integrative Pharmacy, researchers from the School of Medicine, Shenzhen Campus of Sun Yat-sen University, summarized current evidence on how the gut microbiota interacts with radiotherapy.

The review describes a two-way relationship. “Radiotherapy can injure the intestinal lining and change the balance of the gut microbiota. It often reduces microbial diversity, depletes beneficial commensals and expands opportunistic taxa,” explains Jiayuan Huang, corresponding author of the review. “It also disrupts microbial metabolites such as short-chain fatty acids, bile acids and tryptophan-derived compounds, which help maintain the intestinal barrier and immune balance.”

Notably, these changes can create a cycle in which barrier damage, inflammation and microbial imbalance reinforce one another. Conversely, specific microbes and their metabolites may influence how tumors and normal tissues respond to radiation. “Some microbial signals can support antitumor immunity and may increase tumor radiosensitivity, while others may contribute to protecting the intestinal mucosa, reduce inflammation and support epithelial repair,” says Huang.

The authors noted that these effects are context-dependent; the same pathway can have different consequences in tumors and normal tissues.

The review also assesses microbiota-targeted strategies, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, antibiotic modulation, dietary interventions and TCM-derived compounds or formulae. Although these strategies have shown potential in experimental studies and early clinical investigations, further research is needed to clarify their safety, effectiveness and appropriate clinical applications.

“Our review brings together evidence that the gut microbiota is not only affected by radiotherapy but may also influence treatment response and normal-tissue toxicity,” says Huang. “Understanding these interactions may provide new perspectives for developing microbiota-guided strategies in radiotherapy, although more clinical studies are needed before these approaches can be widely applied.”

The authors suggest that future integration of microbiome analysis with radiotherapy research may help identify biomarkers and develop more personalized treatment strategies. “Larger, well-designed trials are needed to evaluate microbiota-targeted interventions alongside standard radiotherapy,” adds Huang.

Contact author details:

Jiayuan Huang, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong 518107, China. Email: huangjy389@mail.sysu.edu.cn

Funder:

This study was supported by the National Natural Science Foundation of China (Grant No. 32300043).

Conflict of interest:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

See the article:

Li R, Huang J. Gut microbiota and radiotherapy: towards enhancing radiotherapy efficacy and mitigating toxicities. Journal of Holistic Integrative Pharmacy. 2026, 7(2): 350-359. https://doi.org/10.1016/j.jhip.2026.05.007