Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer

Author(s):Show less -

Wirbel, Jakob ^[1] ; Pyl, Paul Theodor ^{[2, 3]} ; Kartal, Ece ^{[1, 4]} ; Zych, Konrad ^[1] ; Kashani, Alireza ^[2] ; Milanese, Alessio ^[1] ; Fleck, Jonas S. ^[1] ; Voigt, Anita Y. ^{[1, 5]} ; Palleja, Albert ^[2] ; Ponnudurai, Ruby ^[1] ; Sunagawa, Shinichi ^{[1, 6]} ; Coelho, Luis Pedro ^{[7, 1]} ; Schrotz-King, Petra ^{[8, 9]} ; Vogtmann, Emily ^[10] ; Habermann, Nina ^[11] ; Nimeus, Emma ^{[3, 12]} ; Thomas, Andrew M. ^{[13, 14]} ; Manghi, Paolo ^[14] ; Gandini, Sara ^[15] ; Serrano, Davide ^[15] ; Mizutani, Sayaka ^{[16, 17]} ; Shiroma, Hirotsugu ^[16] ; Shiba, Satoshi ^[18] ; Shibata, Tatsuhiro ^{[18, 19]} ; Yachida, Shinichi ^{[18, 20]} ; Yamada, Takuji ^{[16, 21]} ; Waldron, Levi ^{[22, 23]} ; Naccarati, Alessio ^{[24, 25]} ; Segata, Nicola ^[14] ; Sinha, Rashmi ^[10] ; Ulrich, Cornelia M. ^{[26, 27]} ; Brenner, Hermann ^{[28, 8, 9, 29]} ; Arumugam, Manimozhiyan ^{[30, 2]} ; Bork, Peer ^{[31, 1, 4, 32]} ; Zeller, Georg ^[1]

Affiliation:Show less -

^[1] European Mol Biol Lab, Struct & Computat Biol Unit, Heidelberg - Germany

^[2] Univ Copenhagen, Fac Hlth & Med, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen - Denmark

^[3] Lund Univ, Dept Clin Sci Lund, Fac Med, Div Surg Oncol & Pathol, Lund - Sweden

^[4] Mol Med Partnership Unit, Heidelberg - Germany

^[5] Jackson Lab Genom Med, Farmington, CT - USA

^[6] Swiss Fed Inst Technol, Dept Biol, Zurich - Switzerland

^[7] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Shanghai - Peoples R China

^[8] German Canc Res Ctr, Heidelberg - Germany

^[9] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg - Germany

^[10] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 - USA

^[11] European Mol Biol Lab, Genome Biol Unit, Heidelberg - Germany

^[12] Skane Univ Hosp, Dept Clin Sci Lund, Fac Med, Div Surg, Lund - Sweden

^[13] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[14] Univ Trento, Dept CIBIO, Trento - Italy

^[15] European Inst Oncol IRCCS, IEO, Milan - Italy

^[16] Tokyo Inst Technol, Sch Life Sci & Technol, Tokyo - Japan

^[17] Japan Soc Promot Sci, Tokyo - Japan

^[18] Natl Canc Ctr, Res Inst, Div Canc Genom, Tokyo - Japan

^[19] Univ Tokyo, Inst Med Sci, Lab Mol Med, Human Genome Ctr, Tokyo - Japan

^[20] Osaka Univ, Fac Med, Grad Sch Med, Dept Canc Genome Informat, Osaka - Japan

^[21] Japan Sci & Technol Agcy, PRESTO, Saitama - Japan

^[22] CUNY, Grad Sch Publ Hlth & Hlth Policy, New York, NY 10021 - USA

^[23] CUNY, Inst Implementat Sci Populat Hlth, New York, NY 10021 - USA

^[24] Italian Inst Genom Med, Turin - Italy

^[25] Inst Expt Med, Dept Mol Biol Canc, Prague - Czech Republic

^[26] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT - USA

^[27] Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT - USA

^[28] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg - Germany

^[29] German Canc Res Ctr, German Canc Consortium, Heidelberg - Germany

^[30] Univ Southern Denmark, Fac Hlth Sci, Odense - Denmark

^[31] Max Delbruck Ctr Mol Med, Berlin - Germany

^[32] Univ Wurzburg, Dept Bioinformat, Bioctr, Wurzburg - Germany

• Document type: Journal article
• Source: Nature Medicine; v. 25, n. 4, p. 679+, APR 2019.
• Web of Science Citations: 30

Abstract

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 x 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. (AU)

• FAPESP's process: 16/23527-2 - Identification of microbial biomarkers for colorectal cancer using strain-level metagenomic profiling
• Grantee: Andrew Maltez Thomas
• Support type: Scholarships abroad - Research Internship - Doctorate