Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis

Chen, W.-H.; Lu, H.; Gao, N. L.; Wei, C.; Wang, J.; Tong, F.; Li, H.; Zhang, R.; Ma, H.; Yang, N.; Zhang, Y.; Wang, Y.; Liang, Z.; Zeng, H.; Dong, X.

doi:10.1101/2020.01.06.895490

bioRxiv · 10.1101/2020.01.06.895490

Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis

Chen, W.-H.·Lu, H.·Gao, N. L.·Wei, C.·Wang, J.·Tong, F.·Li, H.·Zhang, R.·Ma, H.·Yang, N.·Zhang, Y.·Wang, Y.·Liang, Z.·Zeng, H.·Dong, X.

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Abstract

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. ResultsWe surveyed the fecal and sputum (as a proxy for lung) microbiota in healthy controls and NSCLC patients of various stages, and found significant perturbations of gut- and sputum-microbiota in patients with NSCLC and DM. Machine-learning models combining both microbiota (mixed models) performed better than either dataset in patient stratification, with the highest area under the curve (AUC) value of 0.842. Sputum-microbiota contributed more than the gut in the mixed models; in addition, sputum-only models performed similarly to the mixed models in most cases. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers. ConclusionOur results indicate that alterations of sputum-microbiota have stronger relationships with NSCLC and distant metastasis than the gut, and strongly support the feasibility of metagenome-based non-invasive disease diagnosis and risk evaluation.

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Chen, W.-H., Lu, H., Gao, N. L., Wei, C., Wang, J., Tong, F., Li, H., Zhang, R., Ma, H., Yang, N., Zhang, Y., Wang, Y., Liang, Z., Zeng, H., Dong, X.. 2020-01-07. Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis. https://doi.org/10.1101/2020.01.06.895490

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