Abstract

Individuals with familial hypercholesterolemia (FH) undergo an aggressive treatment with cholesterol-lowering 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 = 21) and healthy controls (N = 144) was analyzed by extracting DNA from stool samples and sequencing of the V3–V4 region of the 16S rRNA gene. A subgroup (n = 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 = .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 = .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.

摘要

患有家族性高胆固醇血症 (FH) 的个体接受降胆固醇药物的积极治疗以预防冠心病。最近的证据表明肠道菌群、血脂水平和降脂药物之间存在相互作用，但这尚未在 FH 患者中进行研究。该研究的目的是描述家族性高胆固醇血症患者的肠道微生物群，并检查 omega-3 多不饱和脂肪酸 (PUFA) 对血脂的影响是否通过改变肠道微生物群而发挥作用。 通过从粪便样本中提取 DNA 并对 16S rRNA 基因的 V3-V4 区域进行测序，分析了FH ( N  = 21) 和健康对照 ( N = 144)个体的肠道微生物群组成。一个子群 ( n = 15) 的参与者以交叉方式接受了 omega-3 多不饱和脂肪酸 (PUFA) 补充剂或安慰剂，还研究了 PUFA 对肠道微生物群的影响。与健康对照组相比，FH 个体的肠道微生物群组成不同，其特征是丰富度降低 ( p  = .001) 以及属于梭状芽胞杆菌和球菌属的几个属减少。与仅使用他汀类药物的患者相比，除他汀类药物外使用依折麦布的患者似乎具有较低的丰富度（p = .01)。omega-3 PUFA 的干预对微生物群组成的影响可以忽略不计。omega-3 PUFA 干预后对血脂的积极影响与基线肠道微生物群组成或治疗期间肠道微生物的变化无关。此外，与健康对照组相比，FH 患者的肠道菌群发生了改变，这可能是由依折麦布的使用引起的。