RT Journal Article
SR Electronic
T1 Host-microbiome protein-protein interactions reveal mechanisms in human disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 821926
DO 10.1101/821926
A1 Hao Zhou
A1 Juan Felipe Beltrán
A1 Ilana Lauren Brito
YR 2021
UL http://biorxiv.org/content/early/2021/09/04/821926.abstract
AB Host-microbe interactions are crucial for normal physiological and immune system development and are implicated in a wide 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 specific genes involved in pathogeneses, the mechanisms linking them to disease have thus far remained elusive. To identify potential mechanisms through which human-associated bacteria impact host health, we leveraged 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 metagenomic case-control microbiome studies. In nine independent case studies, we find 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. This host-centric analysis strategy provides a mechanistic hypothesis-generating platform for any metagenomics cohort study and extensively adds human functional annotation to commensal bacterial proteins.One-sentence summary Microbiome-derived proteins are linked to disease-associated human pathways by metagenomic and protein-protein interaction analyses.Competing Interest StatementThe authors have declared no competing interest.