A host-microbiota interactome reveals extensive transkingdom connectivity.

Area of Science:

• Microbiology
• Human Physiology
• Proteomics

Background:

• Microorganisms profoundly impact human health, but the molecular mechanisms are poorly understood.
• Pathogens and commensals interact with human proteins (exoproteome) to colonize and modulate host biology.
• Direct exoproteome-microbiota interactions are largely unexplored.

Purpose of the Study:

• To develop and validate a novel technology for large-scale assessment of human exoproteome-microbiome interactions.
• To explore the molecular landscape of host-microorganism interactions.

Main Methods:

• Developed and validated BASEHIT (Bacterial-Associated Secretome-Host Interaction Technology).
• Interrogated over 1.7 million potential interactions between 519 bacterial strains and 3,324 human exoproteins.
• Analyzed binding patterns to infer biological logic and functional roles.

Main Results:

• Discovered an extensive interactome of thousands of novel host-microorganism interactions involving 383 bacterial strains and 651 human proteins.
• Observed specific binding patterns correlating with bacterial phylogeny, tissue origin, and exoprotein specificity.
• Identified strain-specific interactions potentially involved in niche colonization, tissue remodeling, and immunomodulation.

Conclusions:

• Exposes a vast, previously uncharacterized network of molecular interactions between the human exoproteome and resident microbiota.
• Demonstrates that distinct microbial interaction profiles correlate with differential host cell and immune system effects.
• Suggests these molecular interactions are fundamental to the role of indigenous microorganisms in human health and disease.