The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids
Rationale: Evidence suggests the gut microbiome is involved in the development of cardiovascular disease (CVD), with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for CVD from large-scale studies in humans. In particular, there was no strong evidence for association between CVD and aberrant blood lipid levels
Objective: To identify intestinal bacteria taxa, whose proportions correlate with body mass index (BMI) and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, gender and host genetics.
Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and gender, we identified 34 bacterial taxa associated to BMI and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in BMI, 6% in triglycerides, and 4% in high-density lipoproteins (HDL), independent of age, gender and genetic risk factors. A novel risk model including the gut microbiome explained up to 25.9% of HDL variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol.
Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in BMI and blood lipid levels, independent of age, gender and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides and HDL.
- Received May 6, 2015.
- Revision received August 7, 2015.
- Accepted August 11, 2015.
Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.