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.
- MeSH
- adenom genetika mikrobiologie MeSH
- biologické modely MeSH
- databáze genetické MeSH
- druhová specificita MeSH
- feces mikrobiologie MeSH
- kohortové studie MeSH
- kolorektální nádory genetika mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metagenom * MeSH
- nádorové biomarkery metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- střevní mikroflóra genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Research Support, N.I.H., Extramural MeSH
