Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. / Thomas, Andrew Maltez; Manghi, Paolo; Asnicar, Francesco; Pasolli, Edoardo; Armanini, Federica; Zolfo, Moreno; Beghini, Francesco; Manara, Serena; Karcher, Nicolai; Pozzi, Chiara; Gandini, Sara; Serrano, Davide; Tarallo, Sonia; Francavilla, Antonio; Gallo, Gaetano; Trompetto, Mario; Ferrero, Giulio; Mizutani, Sayaka; Shiroma, Hirotsugu; Shiba, Satoshi; Shibata, Tatsuhiro; Yachida, Shinichi; Yamada, Takuji; Wirbel, Jakob; Schrotz-King, Petra; Ulrich, Cornelia M; Brenner, Hermann; Arumugam, Manimozhiyan; Bork, Peer; Zeller, Georg; Cordero, Francesca; Dias-Neto, Emmanuel; Setubal, João Carlos; Tett, Adrian; Pardini, Barbara; Rescigno, Maria; Waldron, Levi; Naccarati, Alessio; Segata, Nicola.
I: Nature Medicine, Bind 25, Nr. 4, 2019, s. 667-678.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation
AU - Thomas, Andrew Maltez
AU - Manghi, Paolo
AU - Asnicar, Francesco
AU - Pasolli, Edoardo
AU - Armanini, Federica
AU - Zolfo, Moreno
AU - Beghini, Francesco
AU - Manara, Serena
AU - Karcher, Nicolai
AU - Pozzi, Chiara
AU - Gandini, Sara
AU - Serrano, Davide
AU - Tarallo, Sonia
AU - Francavilla, Antonio
AU - Gallo, Gaetano
AU - Trompetto, Mario
AU - Ferrero, Giulio
AU - Mizutani, Sayaka
AU - Shiroma, Hirotsugu
AU - Shiba, Satoshi
AU - Shibata, Tatsuhiro
AU - Yachida, Shinichi
AU - Yamada, Takuji
AU - Wirbel, Jakob
AU - Schrotz-King, Petra
AU - Ulrich, Cornelia M
AU - Brenner, Hermann
AU - Arumugam, Manimozhiyan
AU - Bork, Peer
AU - Zeller, Georg
AU - Cordero, Francesca
AU - Dias-Neto, Emmanuel
AU - Setubal, João Carlos
AU - Tett, Adrian
AU - Pardini, Barbara
AU - Rescigno, Maria
AU - Waldron, Levi
AU - Naccarati, Alessio
AU - Segata, Nicola
PY - 2019
Y1 - 2019
N2 - Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.
AB - Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.
U2 - 10.1038/s41591-019-0405-7
DO - 10.1038/s41591-019-0405-7
M3 - Journal article
C2 - 30936548
VL - 25
SP - 667
EP - 678
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 4
ER -
ID: 216515910