A metaproteomics-based meta study of samples from patients with inflammatory bowel disease identifies potential markers for diagnosis and therapy monitoring

2025 · doi:10.1101/2025.11.06.684320
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This paper performed a large-scale meta-study of over 600 fecal metaproteomics samples from patients with inflammatory bowel disease, using bioinformatic reanalysis (Mascot and MMUPHin for batch effect correction) to validate known biomarkers and discover new protein-candidate markers. Across analyses, the authors identified 59 protein groups whose variation was primarily associated with disease rather than laboratory conditions, including Alpha-1-acid glycoprotein that was not previously reported in the original studies, and 53 groups that were differentially abundant in at least one validation dataset. In an independent dataset, 23 successfully validated protein groups, largely derived from human neutrophil vesicles, were significantly associated with remission during treatment, while validation against other disease contexts (e.g., non-alcoholic steatohepatitis, diabetes, colorectal cancer) indicated that individual markers lacked sufficient specificity and that biomarker panels were needed. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract Inflammatory bowel disease (IBD) is a chronic intestinal disorder involving recurring inflammation and pronounced microbial dysbiosis. Comprehensive studies with large patient cohorts are required to Identify meaningful biomarker candidates for diagnosing and monitoring IBD. In this large-scale meta-study of over 600 samples based on fecal metaproteomics, our goal was to validate known biomarkers and discover new candidates. We performed bioinformatic reanalysis using the Mascot search engine and MMUPHin for batch effect correction as well as knowledge graph-enhanced data analysis. We identified 59 protein groups that varied primarily due to disease, rather than laboratory conditions. These included Alpha-1-acid glycoprotein, which was not reported in the original studies. Of these groups, 53 were differentially abundant in at least one of the two validation datasets. Additionally, 23 of the successfully validated protein groups, primarily from human neutrophil vesicles, were found to be significantly associated with remission during treatment in an independent dataset. This finding suggests their potential for disease monitoring. Validation in other disease contexts, such as non-alcoholic steatohepatitis, diabetes, and colorectal cancer, revealed the necessity of biomarker panels, because individual biomarkers could only distinguish IBD from specific conditions. Our results demonstrate the effectiveness of metaproteomics meta-analyses in discovering and validating biomarker panels and assessing their specificity for IBD. Competing Interest Statement The authors have declared no competing interest. Abbreviations - ANOVA - Analysis of Variance - API - Application Programming Interface - CA - Colon Adenoma - DDA - Data-dependent aquisition - DIA - Data-independent aquisition - E.C. - Enzyme Commission - GCA - Gastric Carcinoma - GO - Gene Ontology - HCC - Hepatocellular Carcinoma - IBD - Inflammatory Bowel Disease - IBS - Irritable Bowel Syndrome - KEGG - Kyoto Encyclopedia of Genes and Genomes - LCA - Lowest Common Ancestor - NASH - Nonalcoholic Steatohepatitis - NCBI - National Center for Biotechnology Information - NE - Neutrophil Elastase - Permanova - Permutational Analysis of Variance - PPI - Protein-Protein-Interaction Network - SCFA - Short-Chain Fatty Acid

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