Mining the Human Gut Microbiome for Host-Compatible Anticancer Agents: Implications for Natural Tumor Surveillance

The human microbiome secretes bioactive molecules that modulate host physiology. While commensal biosynthetic potential is established, the role of the microbiome-derived peptides in natural tumor suppression remains underexplored. Driven by the evolutionary host compatibility concept, we hypothesized that commensal peptidome harbors bioactive sequences that selectively suppress aberrant cell growth while maintaining tolerance toward healthy host epithelium. We deployed a consensus-based workflow to mine putative peptides sourced from the human gastrointestinal system in the AMPSphere database. Sequences were scored for physicochemical properties, predicted activity, and ease of synthesis. A 22-mer candidate was selected for synthesis and validation.