Functional microbial shifts and host-microbiome crosstalk in colorectal cancer: insights from a metaproteomic approach

Colorectal cancer (CRC) incidence is increasing in many low- and middle-income countries, including Egypt, partly due to urbanization and lifestyle changes. Metaproteomic approaches remain underutilized in these settings. In this study, we applied fecal metaproteomics in Egyptian CRC patients to characterize disease-associated protein expression patterns, explore host-microbiota functional interactions, and identify metabolic pathways that are altered in the CRC gut environment. Stool samples from 10 CRC patients and 10 healthy controls were analyzed. A total of 441 differentially expressed proteins (DEPs) were identified, of which 406 were consensus proteins overlapping across fold-change analysis, Wilcoxon testing, and PLS-DA. Differential microbial protein expression was primarily associated with core metabolic functions, including carbohydrate, amino acid, and nucleotide transport. Notably, proteins from Segatella copri were markedly suppressed in CRC patients. Functional analysis revealed upregulation of microbial proteins related to DPP-4 and cysteine metabolism, suggesting a possible role of microbiome-derived enzymes in colorectal cancer-associated metabolic and immune modulation, without direct evidence of host translocation.