Mapping the multigenomic human system: structural asymmetry and interface gaps in host-exogenous biological...

Area of Science:

• Host-microbiome interactions
• Systems biology
• Human physiology

Background:

• Host-microbiome research has linked microbial communities to key physiological processes like immunity and metabolism.
• However, the integration of microbial signals into human physiological regulation and the underlying organizational architecture remain unclear.
• Regulatory interfaces connecting microbial ecology to host responses are insufficiently explored.

Purpose of the Study:

• To systematically synthesize host-exogenous biological interactions.
• To map evidence distribution across biological integration levels.
• To evaluate the literature for a coherent multigenomic framework of human physiology.

Main Methods:

• A prospectively registered systematic synthesis using a Work Breakdown Structure (WBS).
• Literature searches categorized into functional coupling, regulatory-interface mediation, and genetic interaction.
• Analysis involved structural mapping, cross-domain convergence, and plausibility assessment of 168 studies.

Main Results:

• Functional host-microbe coupling is well-documented across immune, metabolic, barrier, and neuroendocrine systems.
• Regulatory interfaces, especially membrane-associated signaling and microenvironment dynamics, are under-integrated in current literature.
• Stabilization processes like barrier remodeling and immune recalibration converge at membrane-associated signaling platforms.

Conclusions:

• The human organism can be viewed as a symbiotic multigenomic system integrating signals from multiple genomic sources.
• Membrane-associated signaling interfaces act as critical regulatory nodes integrating ecological, host, and microenvironmental factors.
• A multigenomic systems perspective offers a framework for understanding persistent regulatory configurations in human physiology.