Host genetic variation and its microbiome interactions within the Human Microbiome Project.

Area of Science:

• Human Microbiome Research
• Genomics
• Host-Microbe Interactions

Background:

• Human microbial communities are increasingly linked to health.
• Environmental and molecular interactions shaping these communities are not fully understood.
• Host genetic factors influencing microbiome composition require further exploration.

Purpose of the Study:

• To investigate the role of host genetic factors in shaping the human microbiome.
• To identify specific host genetic variants associated with microbiome composition.
• To create a comprehensive reference dataset for future microbiome-host genetic studies.

Main Methods:

• Whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort.
• Deep characterization of microbiomes across various body sites.
• Identification of millions of single nucleotide variants and insertions-deletions.

Main Results:

• Microbiome taxonomic composition and functional potential covaried with host genetic principal components in the gut and oral sites.
• Specific host genetic variants, including FUT2 secretor status and LCT gene variants, were associated with microbial abundance (e.g., Bifidobacterium longum).
• Associations between host genetics and microbiome features were body-site specific.

Conclusions:

• This study integrates host genome sequencing with existing microbiome data from the HMP.
• It establishes a unique, well-controlled reference for identifying host genetic modulators of the microbiome.
• Findings highlight the potential for discovering body-site specific genetic mechanisms controlling microbiome properties.