Berberine alleviates radiation-induced lung injury via the gut–lung axis

Radiation therapy is a cornerstone of treatment for lung cancer and many other thoracic tumors. However, radiation-induced lung injury (RILI) remains a common and serious complication that can limit treatment intensity and significantly affect patients’ quality of life. In recent years, growing evidence has suggested that the gut microbiota and its metabolites can remotely regulate lung inflammation and tissue repair through systemic circulation. However, the role of the gut microbiota in radiation-induced lung injury has not yet been systematically explored.

 
In this study, the researchers show that berberine alleviates radiation-induced lung injury through a gut microbiota–dependent mechanism. Using a mouse model of thoracic irradiation, they found that berberine treatment reduced lung inflammation, tissue damage, and functional impairment following radiation exposure. Further analyses revealed that these protective effects required the presence of the gut microbiota. Berberine reshaped the radiation-disrupted gut microbial community, with a marked enrichment of Akkermansia muciniphila, and increased levels of the microbiota-derived metabolite inosine. These changes were associated with coordinated molecular responses in lung tissue, including altered gene expression and chromatin states linked to reduced radiation injury. Together, the findings identify the gut–lung axis as a key pathway through which berberine modulates lung responses to radiation.

“Radiation-induced lung injury remains a major challenge in thoracic radiotherapy,” said Dr. Jianxiong Li, Director of the Department of Radiotherapy at the Fifth Medical Center of Chinese PLA General Hospital. “This finding suggests that targeting the gut–lung axis may offer a new way to reduce radiation-related lung damage while preserving the effectiveness of cancer treatment.”

To further contextualize the findings, the researchers examined changes in both gut and lung tissue following radiation exposure and berberine treatment. Radiation was associated with alterations in gut microbial composition and metabolic profiles, while berberine partially mitigated these changes. At the same time, corresponding shifts in gene expression and regulatory patterns were observed in lung tissue. Together, these observations suggest a coordinated relationship between gut-derived signals and lung responses to radiation, consistent with the involvement of the gut–lung axis.

Together, these findings suggest that berberine modulates radiation-induced lung injury through the gut–lung axis, with gut microbiota and microbiota-derived metabolites potentially contributing to the regulation of radiation responses. By linking intestinal microbial changes to molecular and pathological alterations in the lung, this study provides new insight into the biological processes underlying radiation-induced lung injury. Further clinical studies will be required to validate these observations and to explore whether microbiota-informed strategies could be used to improve the assessment and management of radiotherapy-related lung toxicity.

This study was supported by the National Natural Science Foundation of China under grant number 82373515.

About Author:

Dr. Jianxiong Li is a Professor and Director of Radiotherapy Department at the Fifth Medical Center of Chinese PLA General Hospital. He is a nationally recognized expert in radiation medicine and a chief scientist of China’s National Key R&D Program. His research focuses on precision radiotherapy and the mechanisms of radiation-induced lung injury. Dr. Li has published over 40 peer-reviewed papers and holds multiple authorized patents.