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Abstract

The size and composition of the circulating bile acid (BA) pool are important factors in regulating the human gut microbiota. Disrupted regulation of BA metabolism is implicated in several chronic diseases. Bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, previously shown to decrease LDL-cholesterol and increase circulating BA, was investigated for its dose response effect on BA profile in a pilot clinical study. Ten otherwise healthy hypercholesterolemic adults, recruited from a clinical trial site in London, ON, were randomized to consume delayed release or standard release capsules containing L. reuteri NCIMB 30242 in escalating dose over 4 weeks. In another aspect, 4 healthy normocholesterolemic subjects with LDL-C below 3.4 mmol/l received delayed release L. reuteri NCIMB 30242 at a constant dose over 4 weeks. The primary outcome measure was the change in plasma BA profile over the intervention period. Additional outcomes included circulating fibroblast growth factor (FGF)-19, plant sterols and LDL-cholesterol as well as fecal microbiota and bsh gene presence. After one week of intervention subjects receiving delayed release L. reuteri NCIMB 30242 increased total BA by 1.13 ± 0.67 μmol/l (P = 0.02), conjugated BA by 0.67 ± 0.39 μmol/l (P = 0.02) and unconjugated BA by 0.46 ± 0.43 μmol/l (P = 0.07), which represented a greater than 2-fold change relative to baseline. Increases in BA were largely maintained post-week 1 and were generally correlated with FGF-19 and inversely correlated with plant sterols. This is the first clinical support showing that a BSH-active probiotic can significantly and rapidly influence BA metabolism and may prove useful in chronic diseases beyond hypercholesterolemia.

Keywords: bile acid metabolism; bile salt hydrolase; cholesterol; fibroblast growth factor-19; probiotic.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus reuteri NCIMB 30242Increased Conjugated Bile Acid LevelsBeneficial
Moderate
Lactobacillus reuteri NCIMB 30242Increased Total Bile AcidsBeneficial
Moderate
Lactobacillus reuteri NCIMB 30242Increased Unconjugated Bile AcidsNeutral
Small
Lactobacillus reuteri NCIMB 30242Potential Modulation of FGF-19 LevelsBeneficial
Moderate
Lactobacillus reuteri NCIMB 30242Reduced Plant SterolsBeneficial
Moderate
LRC (NCIMB 30242)Increased Circulating Bile Acid LevelsBeneficial
Moderate
LRC (NCIMB 30242)Increased Conjugated Bile Acid LevelsBeneficial
Moderate
LRC (NCIMB 30242)Increased Total Bile Acid LevelsBeneficial
Moderate
LRC (NCIMB 30242)Increased Unconjugated Bile Acid LevelsNeutral
Small
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