Population-level analysis of gut microbiome variation

Area of Science:

• Microbiology
• Human Gut Microbiome Research
• Population Health Studies

Background:

• The variation within the fecal microbiome of the average, healthy population is not well understood.
• Previous studies have not extensively investigated the factors influencing gut microbial composition in large, healthy cohorts.

Purpose of the Study:

• To analyze fecal microbiome variation in healthy individuals using two independent cohorts.
• To identify factors associated with gut microbiota composition and validate findings across datasets.
• To understand the relationship between host covariates and microbial composition.

Main Methods:

• Analysis of two large, phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP) and the Dutch LifeLines-DEEP (LLDeep) study.
• Integration of data with global microbiome datasets for a combined analysis (N=3948).
• Statistical analysis to identify associations between 69 clinical and questionnaire-based covariates and microbiota composition.

Main Results:

• A core microbiota of 14 genera was identified, though total gut diversity remains underexplored.
• Sixty-nine host covariates were associated with microbiota variation, with a 92% replication rate across cohorts.
• Stool consistency had the largest effect size, while medication explained the most variance and interacted with other associations.
• Early-life events like birth mode did not significantly impact adult microbiota composition.

Conclusions:

• Host factors, particularly stool consistency and medication, significantly influence gut microbiome composition in healthy individuals.
• The identified associations between host covariates and microbial composition highlight the need to include these factors in future study designs.
• While a core microbiota exists, significant inter-individual variation persists, indicating a need for further exploration of gut diversity.