Meta‐Analysis Reveals Gut Microbial Signatures in Colorectal Adenoma and A Link with Secondary Bile Acid Conversion

Abstract

BackgroundColorectal adenoma is a common stage during the colorectal cancer (CRC) development. The early diagnosis during adenoma stage could be a key to effectively reduce CRC. Here, we examined the microbial biomarkers of adenoma aiming to identify non‐invasive early diagnosis markers for the prevention of CRC.DesignWe performed a meta‐analysis of four publicly available 16S rDNA datasets with 307 colorectal adenomas, 217 CRC and 252 control samples. Microbial compositions and functions were identified with DADA2 and PICRUSt2 in QIIME2. After adjusting confounding factors, differential analysis was conducted to determine the unbiased significant differential microbes and then Random Forest model was constructed to identify biomarkers. Finally, we applied internal and external validation to assess the diagnostic capabilities with these biomarkers.Results43 differential microbes between adenoma and control were observed. After adjusting the potential confounding factors, 11 of these microbes were identified as biomarkers that could distinguish adenoma from healthy status, with a robust diagnostic accuracy (AUC=0.80). Internal and external validation confirmed the robustness and consistent diagnostic capabilities of these biomarkers with an average AUC of 0.72. Meanwhile, we identified 117 differential microbes between adenoma and CRC. Among them, 26 microbes may serve as biomarkers to separate adenoma from CRC (AUC=0.8), with an average validation AUC of 0.77. Eubacterium ruminantium group was the only one species that appeared in both sets of biomarkers. In addition, multiple microbial functions were altered in microbiome, including secondary bile acid conversion as well as lipopolysaccharide metabolism.ConclusionMeta‐analysis strongly supports that microbial markers can distinguish among CRC, colorectal adenoma and healthy controls and therefore serve as non‐invasive screening tools for the early diagnosis and treatment of CRC. CRC and adenoma specific alterations in the microbial composition and microbial metabolic pathways provide potential targets for the prevention and intervention of CRC.Support or Funding InformationThis work was supported by National Natural Science Foundation of China 81774152 (to RZ) and 81770571 (to LZ).