Exploring the lipid-lowering effects of cinnamic acid and cinnamaldehyde from the perspective of the gut microbiota and metabolites

Abstract

The increasing incidence and associated metabolic complications pose major challenges in the treatment of hyperlipidaemia. Cinnamon is a food and medicinal resource associated with lipid metabolism, but the mechanism by which its active components, cinnamic acid (CA) and cinnamaldehyde (CM), alleviate hyperlipidaemia remains unclear. Biochemical, pathological, gut microbiota, and metabolomic analyses were performed to investigate the effects of CA and CM on HFD-fed mice and the underlying mechanisms involved. Supplementation with CA and CM reduced body weight, liver, and adipose tissue accumulation in HFD-induced mice; improved glucose and lipid metabolism; and decreased inflammation and oxidative stress levels, with CM showing superior efficacy. Faecal microbiota transplantation confirmed that the therapeutic effect was closely related to core gut bacteria and metabolites. Specifically, CA and CM inhibited the growth of lipid metabolism-related genera (<i>e.g.</i>, <i>Turicibacter</i> and <i>Romboutsia</i>) and metabolites (<i>e.g.</i>, PC, LysoPCs, prostaglandin E2, and arachidonic acid) while promoting the growth of beneficial genera (<i>e.g.</i>, <i>Oscillospiraceae</i> and <i>Colidextribacter</i>) and metabolites (<i>e.g.</i>, linoleic acid, phytosphingosine, and stercobilin). Additionally, Spearman's correlation analysis revealed that serum and hepatic lipids, as well as inflammatory factors, were positively correlated with <i>Erysipelatoclostridium</i>, <i>Turicibacter</i>, <i>Eubacterium fissicatena</i>, <i>Enterorhabdus</i>, cervonoyl ethanolamide, and acetoxystachybotrydial acetate, whereas they were negatively correlated with <i>Lachnospiraceae NK4A136</i>, stercobilin, LysoPE (15:0/0:0), and phytosphingosine. In contrast, hepatic oxidative stress markers exhibited the opposite correlation pattern. In conclusion, CA and CM have the potential to regulate the core gut microbiota and metabolites to improve lipid metabolism and decrease related inflammation and oxidative stress levels.