Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer
Sofie Bosch,
Animesh Acharjee,
Mohammed Nabil Quraishi,
Irene V Bijnsdorp,
Patricia Rojas,
Abdellatif Bakkali,
Erwin EW Jansen,
Pieter Stokkers,
Johan Kuijvenhoven,
Thang V Pham,
Andrew D Beggs,
Connie R Jimenez,
Eduard A Struys,
Georgios V Gkoutos,
Tim GJ de Meij,
Nanne KH de Boer
Affiliations
Sofie Bosch
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Endocrinology Metabolism Institute, Amsterdam University Medical Centre, VU University Amsterdam, Amsterdam, The Netherlands
Animesh Acharjee
College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, Birmingham, UK
Mohammed Nabil Quraishi
Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Irene V Bijnsdorp
Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
Patricia Rojas
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Abdellatif Bakkali
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Erwin EW Jansen
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Pieter Stokkers
Department of Gastroenterology and Hepatology, OLVG West, Amsterdam, The Netherlands
Johan Kuijvenhoven
Spaarne Gasthuis, Department of Gastroenterology and Hepatology, Hoofddorp and Haarlem, The Netherlands
Thang V Pham
Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
Andrew D Beggs
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
Connie R Jimenez
Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
Eduard A Struys
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Georgios V Gkoutos
College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, Birmingham, UK
Tim GJ de Meij
Department of Paediatric Gastroenterology, AG&M Research Institute, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
Nanne KH de Boer
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Endocrinology Metabolism Institute, Amsterdam University Medical Centre, VU University Amsterdam, Amsterdam, The Netherlands
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.
