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Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer

  • Amsterdam UMC
  • University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
  • University Hospitals Birmingham NHS Foundation Trust
  • University of Birmingham
  • NIHR Birmingham Biomedical Research Centre, Birmingham, UK
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • Onze Lieve Vrouwe Gasthuis
  • Health Data Research UK
  • NIHR Experimental Cancer Medicine Center
  • Vrije Universiteit Amsterdam
  • University Hospital Birmingham
  • VU Medical Center
  • Department of Gastroenterology and Hepatology
  • MRC Health Data Research UK (HDR UK)
  • University of Birmingham, Birmingham, United Kingdom
  • VU University Medical Center
  • Onze Lieve Vrouwe Gasthuis (OLVG)
  • Spaarne Gasthuis

Research output: Contribution to journalArticleAcademicpeer-review

94 Downloads (Pure)

Abstract

Background: Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions. Methods: This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms. Results: Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity. Conclusions: Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.
Original languageEnglish
Article number2139979
Pages (from-to)2139979
JournalGut microbes
Volume14
Issue number1
DOIs
Publication statusPublished - 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Colon cancer
  • adenoma
  • biomarker
  • data integration
  • multi omics
  • screening
  • stool
  • Humans
  • Proteome/analysis
  • Colorectal Neoplasms/diagnosis
  • Chromatography, Liquid
  • RNA, Ribosomal, 16S
  • Amino Acids
  • Gastrointestinal Microbiome
  • Tandem Mass Spectrometry
  • Adenoma/diagnosis
  • Feces/chemistry

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