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Summary

Radiotherapy (RT) is a mainstay treatment for non-small cell lung cancer. Several studies have shown a benefit in local control and survival increasing biological equivalent doses_. However, its effectiveness is limited by the risk of radiation-induced lung injury or toxicity which is the result of an abnormal healing response to lung irradiation caused by damage to parenchymal cells, vasculature, and/or stroma followed by immune cell activation. Radiation pneumonitis and pulmonary fibrosis represent the acute and late phase of radiation-induced lung injury. Emerging evidence indicates that gut bacteria are associated with the response to RT but also with RT toxicity. However, the role of the host microbiome in balancing protective or adverse effects of RT in the lung remains to be explored. Thus, in the present proposal we want to determine whether thoracic RT induces an alteration in the lung and gut microbiome; whether an altered lung or gut microbiome initiates radiation-induced disease pathogenesis, promotes acute and chronic inflammation, or is merely a marker of injury and inflammation; whether the microbiome can be manipulated to change RT induced lung disease progesssen; and which bacterial metabolites are involved in these processes.

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