Host-microbiome protein-protein interactions capture disease-relevant pathways

Background Host-microbe interactions are crucial for normal physiological and immune system development and are implicated in a variety of diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), obesity, and type 2 diabetes (T2D). Despite large-scale case-control studies aimed at identifying microbial taxa or genes involved in pathogeneses, the mechanisms linking them to disease have thus far remained elusive. Results To identify potential pathways through which human-associated bacteria impact host health, we leverage publicly-available interspecies protein-protein interaction (PPI) data to find clusters of microbiome-derived proteins with high sequence identity to known human-protein interactors. We observe differential targeting of putative human-interacting bacterial genes in nine independent metagenomic studies, finding evidence that the microbiome broadly targets human proteins involved in immune, oncogenic, apoptotic, and endocrine signaling pathways in relation to IBD, CRC, obesity, and T2D diagnoses. Conclusions This host-centric analysis provides a mechanistic hypothesis-generating platform and extensively adds human functional annotation to commensal bacterial proteins.

Automated summary

This study explores the potential mechanisms through which human-associated bacteria affect host health, with a focus on diseases such as IBD, CRC, obesity, and T2D. By leveraging publicly available data and analyzing metagenomic studies, the researchers identify differential targeting of bacterial genes that interact with human proteins involved in immune, oncogenic, apoptotic, and endocrine signaling pathways. This host-centric analysis provides valuable insights into the role of the microbiome in disease development.