Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

• Published in: Nutrients 2020-06, Vol.12 (6), p.1837
• Main Authors: Navarro, Sandi L, Levy, Lisa, Curtis, Keith R, Elkon, Isaac, Kahsai, Orsalem J, Ammar, Hamza S, Randolph, Timothy W, Hong, Natalie N, Carnevale Neto, Fausto, Raftery, Daniel, Chapkin, Robert S, Lampe, Johanna W, Hullar, Meredith A J
• Format: Article
• Language: English
• Subjects: Acids; Adult; Bacteria; Bile; Bile acids; Bile Acids and Salts - blood; Chromatography, Liquid; Chronic illnesses; Cross-Over Studies; Cross-Sectional Studies; Disease; Double-Blind Method; Excretion; Female; Flax - metabolism; Gas flow; Gene expression; Humans; Intervention; Lignans; Lignans - metabolism; Lignans - pharmacology; Liver; Male; Mass Spectrometry; Medical research; Metabolism; Metabolites; Microorganisms; Middle Aged; Plant Extracts - metabolism; Plant Extracts - pharmacology; Plasma; Randomization; Skin cancer; Urine; Young Adult
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12061837

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20-45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.