@article{83ad771d846e485c9cae60501bd850d6,
title = "Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer",
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.",
keywords = "Adenoma/diagnosis, Amino Acids, Chromatography, Liquid, Colon cancer, Colorectal Neoplasms/diagnosis, Feces/chemistry, Gastrointestinal Microbiome, Humans, Proteome/analysis, RNA, Ribosomal, 16S, Tandem Mass Spectrometry, adenoma, biomarker, data integration, multi omics, screening, stool",
author = "Sofie Bosch and Animesh Acharjee and Quraishi, {Mohammed Nabil} and Bijnsdorp, {Irene V.} and Patricia Rojas and Abdellatif Bakkali and Jansen, {Erwin E. W.} and Pieter Stokkers and Johan Kuijvenhoven and Pham, {Thang V.} and Beggs, {Andrew D.} and Jimenez, {Connie R.} and Struys, {Eduard A.} and Gkoutos, {Georgios V.} and {de Meij}, {Tim G. J.} and {de Boer}, {Nanne K. H.}",
note = "Funding Information: This is incorrect. An error has occured three times whilst completing the APA. The following disclosures should be restored: S Bosch has nothing to declare. A Acharjee has nothing to declare. MN Quraishi has nothing to declare, I Bijnsdorp nothing to declare, Patricia Rojas has nothing to declare, A Bakkali has nothing to declare. EEW Jansen has nothing to declare. P Stokkers has nothing to declare. J Kuyvenhoven has served as a consultant for Janssen Pharmaceuticals. TV Pham has nothing to declare. A Beggs has received travel funding and honoraria from Illumina Inc. Bristol-Myers-Squibb and Ono Pharma. C Jimenez has nothing to declare. EA Struys has nothing to declare. Georgios V Gkoutos has nothing to declare. TGJ de Meij has served as a speaker for Mead Johnson. He has received a (unrestricted) research grant from Danone and MLDS. NKH de Boer has served as a speaker for AbbVie and MSD. He has served as consultant and/or principal investigator for TEVA Pharma BV and Takeda. He has received a (unrestricted) research grant from Dr. Falk, TEVA Pharma BV, Takeda and MLDS. Funding Information: We thank all study participants for their willingness to provide for fecal samples. Furthermore, we would like to thank Sander R Piersma for the mass spectrometry analysis during the protein measurements, Marina Brizzio Brentar with her help on the database. GVG and AA acknowledge support from support from NIHR Birmingham SRMRC, NIHR Birmingham ECMC, Nanocommons H2020-EU (731032) and the NIHR Birmingham Biomedical Research Center and the MRC HDR UK (HDRUK/CFC/01), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Medical Research Council or the Department of Health. Funding Information: This study was funded by the Dr C. J. Vaillant Fonds. In addition, we received an unrestricted grant from Takeda Pharmaceuticals. ADB is currently supported by a Cancer Research UK Advanced Clinician Scientist award (ref C31641/A23923) and his laboratory is supported by the CRUK Center Birmingham (C17422/A25154) and the Birmingham Experimental Cancer Medicine Center (C11497/A25127). MS infrastructure was funded by the Cancer Center Amsterdam and the Netherlands Organization for Scientific Research (NWO-Middelgroot project number 91116017);takeda [NA; DR VaillantfondsDR Vaillantfonds [NA]; We thank all study participants for their willingness to provide for fecal samples. Furthermore, we would like to thank Sander R Piersma for the mass spectrometry analysis during the protein measurements, Marina Brizzio Brentar with her help on the database. GVG and AA acknowledge support from support from NIHR Birmingham SRMRC, NIHR Birmingham ECMC, Nanocommons H2020-EU (731032) and the NIHR Birmingham Biomedical Research Center and the MRC HDR UK (HDRUK/CFC/01), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Medical Research Council or the Department of Health. Publisher Copyright: {\textcopyright} 2022 Amsterdam UMC, Amsterdam, The Netherlands. Published with license by Taylor & Francis Group, LLC.",
year = "2022",
doi = "https://doi.org/10.1080/19490976.2022.2139979",
language = "English",
volume = "14",
pages = "2139979",
journal = "Gut Microbes",
issn = "1949-0976",
publisher = "Landes Bioscience",
number = "1",
}