Functional Microbial Shifts and Host-Microbiome Crosstalk in Colorectal Cancer: Evidence from a Metaproteomic Approach

Colorectal cancer incidence is surging in many low- and middle-income countries, including Egypt, partly due to urbanization and lifestyle changes. Metaproteomics remains underutilized in such settings. This study applies a metaproteomic approach to fecal samples from Egyptian CRC patients to identify functional protein biomarkers, characterize host microbiota interactions, and uncover dysregulated metabolic pathways associated with cancer progression. Stool samples from 10 CRC patients and 10 healthy controls were analyzed. A total of 441 differentially expressed proteins (DEPs) were identified, with 406 consensus proteins intersected from fold change, Wilcoxon test, and PLS-DA analysis. COG-based enrichment revealed significant downregulation of proteins related to core microbial metabolic processes (e.g., carbohydrate, amino acid, inorganic ions and nucleotide transport). Notably, proteins from Segatella copri were markedly suppressed in CRC patients. Functional analysis revealed upregulation of microbial proteins related to DPP4 and cysteine, supporting the previous hypothesis of their translocation to the host, promoting tumor progression.