Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota.

PURPOSE: To investigate the effect of virgin olive oil phenolic compounds (PC) alone or in combination with thyme PC on blood lipid profile from hypercholesterolemic humans, and whether the changes generated are related with changes in gut microbiota populations and activities. METHODS: A randomized, controlled, double-blind, crossover human trial (n = 12) was carried out. Participants ingested 25 mL/day for 3 weeks, preceded by 2-week washout periods, three raw virgin olive oils differing in the concentration and origin of PC: (1) a virgin olive oil (OO) naturally containing 80 mg PC/kg, (VOO), (2) a PC-enriched virgin olive oil containing 500 mg PC/kg, from OO (FVOO), and (3) a PC-enriched virgin olive oil containing a mixture of 500 mg PC/kg from OO and thyme, 1:1 (FVOOT). Blood lipid values and faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites were analysed. RESULTS: FVOOT decreased seric ox-LDL concentrations compared with pre-FVOOT, and increased numbers of bifidobacteria and the levels of the phenolic metabolite protocatechuic acid compared to VOO (P < 0.05). FVOO did not lead to changes in blood lipid profile nor quantitative changes in the microbial populations analysed, but increased the coprostanone compared to FVOOT (P < 0.05), and the levels of the faecal hydroxytyrosol and dihydroxyphenylacetic acids, compared with pre-intervention values and to VOO, respectively (P < 0.05). CONCLUSION: The ingestion of a PC-enriched virgin olive oil, containing a mixture of olive oil and thyme PC for 3 weeks, decreases blood ox-LDL in hypercholesterolemic humans. This cardio-protective effect could be mediated by the increases in populations of bifidobacteria together with increases in PC microbial metabolites with antioxidant activities.This work was supported by Instituto de Salud Carlos III FEDER (RD12-0042, CB06/03/0028, CD10/00224, CP06/00100, CB06/02/0029, CA11/00215), Ministry of Economy and Competitiveness (AGL2012-40144-C03-01, AGL2012-40144-C03-02, AGL2012-40144-C03-03, FPI:BES- 2010-040766), Agency for Management of University and Research Grants (2009 SGR 1195, 2014 SGR 240). We thank M Angels Calvo for the growth of pure cultures, Malén Massot for helping us in the elaboration of the FISH-FC protocol, Óscar Fornas and Cristina Llop for their technical assistance and Borges Mediterranean Group.http://dx.doi.org/10.1007/s00394-015-1063-