Integrative Analysis of Fecal Metagenomics and Metabolomics in Colorectal Cancer

Although colorectal cancer (CRC) is the second leading cause of death in developed countries, its diagnostics tests for early disease stages are suboptimal. We have performed a combination of UHPLC-MS metabolomics and 16S microbiome analyses in 224 feces samples in order to identify early biomarkers for both advanced adenomas (AD) and CRC. We report differences in fecal levels of cholesteryl esters and sphingolipids in CRC. We identified Fusobacterium, Parvimonas and Staphylococcus to be increased in CRC patients and Lachnospiraceae family to be reduced. We finally described Adlercreutzia to be more abundant in AD patients’ feces. Integration of metabolomics and microbiome data revealed tight interactions between bacteria and host and performed better than FOB test for CRC diagnosis. This study identifies potential early biomarkers that outperform current diagnostic tools and frame them into the established gut microbiota role in CRC pathogenesis. Funding Statement: Centro de Investigacion Biomedica en Red en el Area tematica de Enfermedades Hepaticas y Digestivas (CIBERehd) is funded by the Institute of Health Carlos III. This work has been supported by Instituto de Salud Carlos III (PI12/01604 to JMF-P, PI11/0094 and PI17/00837 to JC), BG2016-INVESTIGACION COLABORATIVA EN MEDICINA DE PRECISION Y BIOMARCADORES (Ref. KK-2016/00026) funded by Basque Government and from Programa Interreg V-A Espana-Portugal 2014-2020 (POCTEP), 0181_NANOEATERS_1_EP to JC. All of them co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of Galicia (Code 2011/038).