Cross-body site microbial interactions influence the human plasma metabolome

Area of Science:

• Microbiome research
• Metabolomics
• Host-microbiome interactions

Background:

• The human microbiome significantly impacts host metabolism and health.
• Previous studies primarily focused on the gut microbiome in isolation.
• A holistic view of how microbiomes from diverse body sites interact to shape host metabolism is needed.

Purpose of the Study:

• To systematically analyze the individual and combined effects of microbiomes from multiple body sites on the human plasma metabolome.
• To investigate microbial interactions and their role in metabolic regulation.
• To explore the link between microbiome-metabolome axis and metabolic diseases like insulin resistance.

Main Methods:

• Analysis of data from three independent human cohorts (n=435).
• Systematic analysis of plasma metabolome (814 metabolites) in relation to microbiomes from gut, oral, skin, and nasal sites.
• Application of machine learning and mediation analyses to identify microbial interactions and metabolic pathways.

Main Results:

• Microbiomes from all analyzed body sites collectively explained 30.13% of plasma metabolome variation.
• The gut microbiome had the largest individual contribution (18.44%), followed by oral, skin, and nasal microbiomes.
• Widespread cooperative and synergistic microbial interactions were observed, particularly along the oral-gut axis, influencing over half of the metabolites.
• This axis was amplified in insulin resistance, linking microbial cooperation to metabolic dysregulation.

Conclusions:

• Microbiome-metabolome relationships are systemic and interactive, involving microbiomes from multiple body sites.
• Integrating spatially distributed microbial ecosystems is crucial for understanding host metabolic regulation and disease.
• The oral-gut microbiome-metabolome axis plays a significant role in metabolic health and disease, particularly in insulin resistance.