Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis

Objectives: The purpose of this study was to explore the effect of trimethylamine (TMA)-degrading probiotic agents on trimethylamine oxide (TMAO) and the related lipid metabolism in mice. Methods: Ten lipid-lowering strains were detected with TMA-degradation capacity in vitro. After probiotic intervention for the mice on a high-choline diet, TMA content in cecum and TMA and TMAO in serum was explored, as well as the expression of key gene flavin-containing monooxygenase 3 (FMO3) of the TMA-TMAO metabolism. The expression of genes related to the lipid metabolism was also investigated by realtime polymerase chain reaction and Western blot. Finally, the colonization of functional strains in the intestine were examined. Results: Five of 10 lipid-lowering strains effectively degraded TMA in vitro, and the TMA level in the cecum of mice were reduced after probiotic intervention. TMA level and TMAO in serum were also significantly reduced by the strains (P < 0.05), but not due to the regulation of FMO3. Probiotic agents could improve the lipid metabolism by acting on the Farnesoid X receptor and cholesterol 7-alpha hydroxy-lase. Among the strains, Bifidobacterium animalis subsp. lactis F1-3-2 showed the most prominent performance and colonized in the cecum of mice. Conclusions: Bif. animalis subsp. lactis F1-3-2 could be colonized in the cecum, and might directly degrade TMA or change the structure of intestinal flora. The strain had an effect on TMA and TMAO levels in vivo by decreasing cecum TMA. The strain was demonstrated to participate in the TMA-TMAO regulation, improve the lipid metabolism, and alleviate atherosclerosis caused by TMAO. However, FMO3 had not changed in this process, and needs further study. (C) 2020 Elsevier Inc. All rights reserved.