An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults

Abstract

Coronary heart disease (CHD) is one of the major causes of death and disability in industrialised countries, with elevated blood cholesterol an established risk factor. Total plasma cholesterol reduction in populations suffering from primary hypercholesterolemia may lower CHD incidence. This study investigated the cholesterol reducing capacity of Lactobacillus plantarum ECGC 13110402, a strain selected for its high bile salt hydrolase activity, in 49 normal to mildly hypercholesterolaemic adults. Primary efficacy outcomes included effect on blood lipids (total cholesterol (TC), low density lipoproteins (LDL-C), high density lipoproteins (HDL-C) and triacylgycerides (TAG), inflammatory biomarkers and occurrence/severity of gastrointestinal side effects to establish safety and tolerance of the intervention. Secondary outcomes included blood pressure, immune biomarkers, gut microbiota characterisation and metabonome changes. The study was run in a parallel, double blind, placebo controlled, randomised design in which the active group ingested 2x109 CFU encapsulated Lactobacillus plantarum ECGC 13110402 twice daily. Daily ingestion of the active treatment resulted in a statistically significant reduction in LDL-C in volunteers with baseline TC<5mM during the 0-12 week period (13.9%, P = 0.030), a significant reduction in TC in volunteers with baseline TC≥6mM in the 0-6 week period (37.6%, P = 0.045), a significant decrease in TAG (53.9% P = 0.030) and an increase in HDL-C (14.7%, P = 0.007) in the over 60 years population in the 6-12 week period. A statistically significant reduction in systolic blood pressure was also observed across the active study group in the 6-12-week period (6.6%, P = 0.003). No impact on gastrointestinal function and side effects was observed during the study. Similar to blood and urine metabonomic analyses, faecal metagenomics did not reveal significant changes upon active or placebo intake. The results of this study suggest that Lactobacillus plantarum ECGC 13110402 is a well-tolerated, natural probiotic, that may be used as an alternative or supplement to existing treatments to reduce cardiovascular risk.

Trial registration: Clinical trials.gov NCT03263104.

Conflict of interest statement

Competing Interests: This study was supported by Optibiotix Health plc. Optibiotix Health plc provided support in the form of salary for author Sofia Kolida, as well as the probiotic used within this research. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow of the study participants through the intervention.

Fig 2

(A) Histograms representing the relative abundance at family level of the mean between all the samples underwent to the same treatment (A: Lactobacillus plantarum ECGC 13110402) at different time point (B = basal, V1 = visit 1, V2 = visit 2, V3 = visit 3, V4 = visit 4). Relative abundances were filtered in order to keep those families that were founded in at least 10% of the subjects at 0.01% of abundance. Legend reports family names according to Greengenes syntax. (B) Histograms representing the relative abundance at family level of the mean between all the samples underwent to the same treatment (B: placebo) at different time point (B = basal, V1 = visit 1, V2 = visit 2, V3 visit 3, V4 = visit 4). Relative abundances were filtered in order to keep those families that were founded in at least 10% of the subjects at 0.01% of abundance. Legend reports family names according to Greengenes syntax.

Fig 3. (A) A PCA scores plot for urinary metabolites for all treatments (A: Lactobacillus plantarum ECGC 13110402 and B: placebo) and baseline (V1) and 12 weeks (V3) (n = 91); (B) A PCA scores plot for urinary metabolites for all treatments (A: Lactobacillus plantarum ECGC 13110402 and B: placebo) (A and B) and baseline (V1) and 12 weeks (V3) (n = 86).

Fig 4. A PCA scores plot for serum metabolites at baseline comparing treatments A and B (A: Lactobacillus plantarum ECGC 13110402 and B: placebo) (A); A PCA scores plot for serum metabolites at 12 weeks comparing treatments A and B (A: Lactobacillus plantarum ECGC 13110402 and B: placebo) (B).