Bacterial strains in the human gut associate with host physiology

Area of Science:

• Microbiome research
• Genetics
• Human physiology

Background:

• The human microbiota significantly impacts host physiology.
• Microbial complexity extends beyond species identification to strain-level variations.
• Understanding intra-species genetic diversity is crucial for comprehending host-microbe interactions.

Purpose of the Study:

• To analyze the intra-species genetic diversity of gut bacteria across a large, multi-national cohort.
• To investigate the relationship between bacterial strain abundance, genetic stability, and ecological behavior.
• To map strain-level microbial associations with host physiological traits.

Main Methods:

• Analysis of genetic diversity in 936 gut bacterial species from 24,997 individuals.
• Correlation of strain abundance with intra-clonal mutation rates.
• Association of strain ecological strategies (coexistence vs. exclusion) with specific gene functions.
• Integration of deep phenotypic data to link bacterial strains with host physiology.

Main Results:

• Highly abundant gut bacterial species showed greater strain stability.
• Low-abundance species exhibited increased in-clonal mutations.
• Mutually exclusive strains were often clonal, while genetically variable strains tended to coexist.
• Strain turnover correlated with chemotaxis and sporulation genes; coexistence with quorum sensing and secretion systems.
• An atlas of strain-level associations with host traits was created, linking specific bacteria (e.g., *Phocaeicola vulgatus*, *Lachnospira eligens*, *Parabacteroides distasonis*) to obesity, sleep, and iron homeostasis.

Conclusions:

• Gut bacterial strain diversity is a key determinant of microbial ecology and host interactions.
• Specific genetic elements within bacterial strains influence their ecological dynamics and host associations.
• The developed resource provides a foundation for personalized microbiome interventions targeting specific host health outcomes.