Reduced gut microbial diversity in familial hypercholesterolemia with no effect of omega-3 polyunsaturated fatty acids intervention–a pilot trial

Abstract

Individuals with familial hypercholesterolemia (FH) undergo an aggressive treatment with cholesterollowering drugs to prevent coronary heart disease. Recent evidence suggests an interplay between the gut microbiota, blood lipid levels and lipid-lowering drugs, but this has yet to be studied in individuals with FH. The objective of the study was to characterize the gut microbiota of individuals with familial hypercholesterolemia and examine if effects of omega-3 polyunsaturated fatty acids (PUFAs) on blood lipids act through modification of the gut microbiome. The gut microbiota composition of individuals with FH (N ¼ 21) and healthy controls (N ¼ 144) was analyzed by extracting DNA from stool samples and sequencing of the V3–V4 region of the 16S rRNA gene. A subgroup (n ¼ 15) of the participants received omega-3 polyunsaturated fatty acids (PUFAs) supplementation or placebo in a crossover manner, and the effect of PUFAs on the gut microbiota was also investigated. Individuals with FH had a different gut microbiota composition compared to healthy controls, characterized by reduced richness (p ¼ .001) and reduction of several genera belonging to Clostridia and Coriobacteriia. Patients using ezetimibe in addition to statins appeared to have lower richness compared to those only using statins (p ¼ .01). Intervention with omega-3 PUFAs had negligible impact on the microbiota composition. Positive effects on blood lipids after intervention with omega-3 PUFA were not associated with baseline gut microbiota composition or gut microbial changes during treatment. Further, patients with FH have an altered gut microbiota compared to healthy controls, possibly driven by the use of ezetimibe.