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

Abstract

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.

Multi-omics in Crohn's disease: New insights from inside

“…The abundance of Agathobacter rectalis (OTU 120) in ileum was negatively correlated with the expression of antimicrobial CXCL6 and chemokine CCL20 , so was the abundance of Streptococcus (OTU 37) and Eikenella (OTU 39) in rectum. A recent host-centered study has identified microbiome-derived protein clusters with high sequence identity to human protein-protein interactions (PPIs) by collecting existing interspecies PPIs data [170] . By combining PPIs with metagenome analysis, host functional annotations were added to microbiome-related diseases such as IBD, so as to provide a more reliable reference for the study of disease mechanism and promising therapeutic molecular targets.…”

Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach withPlesiomonas shigelloides

“…In the case of bacteria, 25-50% of the genome comprises HPs, which may have roles in disease and therapeutic targets because they are involved in the pathogenesis of a disease or the regulation of a biological pathway [20]. Hypothetical proteins also have roles in microbial interactions by affecting the expression, regulation or function of other proteins in the host or the microbiome [21, 22]. Some methods to predict the function of hypothetical proteins using big data and machine learning are based on clustering the proteins based on their sequence similarity or interaction patterns [20, 22].…”

“…Hypothetical proteins also have roles in microbial interactions by affecting the expression, regulation or function of other proteins in the host or the microbiome [21, 22]. Some methods to predict the function of hypothetical proteins using big data and machine learning are based on clustering the proteins based on their sequence similarity or interaction patterns [20, 22].…”

Ginsenoside Compound K Ameliorates Development of Diabetic Kidney Disease through Inhibiting TLR4 Activation Induced by Microbially Produced Imidazole Propionate

“…On the other hand, protein is one of the essential elements for maintaining basic functions and processes in humans. Therefore, excessive protein restriction is not advised for the prevention of early renal function decline [ 17 ]. We prefer the regulation of intestinal flora and reducing pathogenic effects of endotoxin as possible effective managing strategies for DKD.…”