Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment

This study aims to elucidate the impact of gut microbiota alterations on tumorigenesis and immune response in lung adenocarcinoma (LUAD). Using Gprc5a-/- mice as a model, we performed fecal microbiota transfer (FMT) from Gprc5a-/- and Gprc5a-/-; Lcn2-/- donors to investigate the role of gut microbiome changes in modulating tumor growth and the immune microenvironment. Single-cell RNA sequencing (scRNA-seq) was conducted on colonic lamina propria and subcutaneous tumor tissues. Our findings demonstrate that gut microbiota from Lcn2-deficient mice promotes systemic inflammation and immunosuppression, enhancing tumor progression. This study provides insights into the microbiome's influence on LUAD and potential therapeutic strategies targeting microbiome-related pathways. Overall design: Single-cell RNA sequencing (scRNA-seq) profiling was performed on colonic lamina propria and subcutaneous tumor tissues from Gprc5a-/- syngeneic mice treated with fecal microbiota transfer (FMT) from either Gprc5a-/- or Gprc5a-/-; Lcn2-/- donors. Mice were grouped based on the source of FMT and included both male and female subjects (n = 2 mice per group). Freshly collected tissues were dissociated into single-cell suspensions, and live cells were sorted to exclude dead cells.