Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colore...
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| Published in | Nature medicine Vol. 25; no. 4; pp. 679 - 689 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.04.2019
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Summary: | Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC,
n
= 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10
−5
). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
Cross-study analysis defines fecal microbial species associated with colorectal cancer. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 G.Z., M.A., P.B. conceived and supervised the study. P.S.-K., N.H., C.M.U., H.B., E.V., R.S. recruited patients and collected samples. E.K., A.Y.V., S.Sunagawa, P.B. generated metagenomic data. A.M., P.T.P., J.S.F., A.P., S.Sunagawa, L.P.C., G.Z., M.A. developed metagenomic profiling workflows and/or performed taxonomic and functional profiling. J.W., G.Z., K.Z., P.T.P., A.K., M.A., N.S. performed statistical analysis and/or developed statistical analysis workflows. E.K. and R.P.P. designed and performed validation experiments, A.M.T., P.M., S.G., D.S., S.M., H.S., S.Shiba, T.S., S.Y., T.Y., L.W., A.N., N.S. provided additional validation data, J.W., G.Z., M.A., P.T.P., P.B. designed figures. G.Z., J.W., M.A., P.B., wrote the manuscript with contributions from P.T.P., A.M., S.Sunagawa, L.P.C., E.K., A.Y.V., E.V., R.S., P.S.K., H.B., E.N., N.S., L.W. All authors discussed and approved the manuscript. These authors contributed equally to the work. Present Address: Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China Author Contributions |
| ISSN: | 1078-8956 1546-170X |
| DOI: | 10.1038/s41591-019-0406-6 |