Impact of Gut Microbiome Alterations on Lung Cancer Progression
The goal of this study is to investigate the role of gut microbiome alterations in the progression of lung adenocarcinoma (LUAD) and to understand the underlying mechanisms by which these changes impact tumor development and the tumor microenvironment (TME) in distant tumors external to the gut. Using fecal microbiota transfer (FMT) models, 16S rRNA gene sequencing, and immunological analyses, we delineated a pathway by which gut microbiome alterations, incurred by the loss of the antimicrobial protein Lcn2, foster the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagates systemically, exerting immunosuppression within the TME, augmenting tumor growth through an IL-6-dependent mechanism, and dampening the response to immunotherapy. The findings underscore the significant role of the gut-lung tumor axis in LUAD progression and highlight potential therapeutic targets within the microbiome. This work also provides insights into the mechanisms by which gut microbiome-induced inflammation influences lung cancer and its response to immunotherapy.