Abstract
Variation in the human gut microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the gut microbiota and abdominal adiposity using body composition as measured by Dual X-Ray Absorptiometry (DXA) in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.
Results
We profile six adiposity measures in 3,666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android:gynoid ratio. We confirm the association of lower diversity with obesity and adiposity measures and then compare the association between gut microbial composition and the adiposity phenotypes in a discovery sub-sample of twins. We identify associations between the relative abundances ofgut microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI asa surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project, and the extended TwinsUK cohort. Meta-analysis across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.
Results
We profile six adiposity measures in 3,666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android:gynoid ratio. We confirm the association of lower diversity with obesity and adiposity measures and then compare the association between gut microbial composition and the adiposity phenotypes in a discovery sub-sample of twins. We identify associations between the relative abundances ofgut microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI asa surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project, and the extended TwinsUK cohort. Meta-analysis across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.
| Original language | English |
|---|---|
| Article number | 189 |
| Journal | GENOME BIOLOGY |
| Volume | 17 |
| Issue number | 1 |
| Early online date | 26 Sept 2016 |
| DOIs | |
| Publication status | Published - 26 Sept 2016 |
Keywords
- fecal microbiome
- obesity
- visceral fat
- heritability
- genetic association
- twins
