Knowledge of the gut microbiome has expanded recently owing to next-generation sequencing techniques. Consequently, the relationship between the human gut microbiome and various host disorders has become clear. Previous studies have reported a higher presence of coronary artery disease (CAD) in patients with specific enterotypes of the gut microbiome [1,2]. Generally, the individual gut microbiome is known to be resilient and remains stable in the long term [3], and several specific gut bacteria are associated with CAD [4], suggesting that individual gut microbiome features could be a potential predictor for the development of CAD. In addition, the gut microbiome generates several metabolites that have physiological effects on the host. For instance, trimethylamine N-oxide (TMAO) is widely known to be a risk factor for atherosclerosis [[5], [6], [7]]. Butyrate from the gut microbiome has anti-inflammatory effects that may suppress atherogenesis [8].

In a recent study, the metabolic pathway of linoleic acid in Lactobacillus plantarum became clear [9]. In this pathway, linoleic acid is converted to oleic acid via 10-hydroxy-cis-12-octadecenoic acid (HYA), 10-oxo-cis-12-octadecenoic acid (KetoA), 10-oxo-trans-11-octadecenoic acid (KetoC), 10-oxo-octadecenoic acid (KetoB), 10-hydroxy-octadecenoic acid (HYB). HYB and KetoB are also generated from oleic acid. Lactobacillus is among the most common bacteria in the human gastrointestinal tract, and linoleic and oleic acids are among the most highly consumed unsaturated fatty acids in the human diet. A recent report showed that the levels of the early metabolites of this pathway in the colon, small intestine, and plasma are notably lower in germ-free mice [9], showing that the generation of these lipid metabolites may depend not on the host but on the gut microbiome. Some in vitro studies have reported the physiological effects of metabolites in this pathway. All hydroxy and oxo fatty acids in this pathway activate proliferator-activated receptor (PPAR)α, and KetoA activates both PPARα and PPARγ [10]. Another study demonstrated that KetoC has antioxidant and anti-inflammatory effects [11,12]. In addition, HYA and KetoA have hypolipidemic effects [13], and HYA administration in mice improves glucose homeostasis [14].

These results indicate that the unique linoleic acid metabolites generated by the gut microbiome might suppress host atherogenesis. However, no clinical study has evaluated the effects of these metabolites on CAD development. In addition, the stability of these metabolites in human blood over time and their relationship with other patient characteristics remain unclear. Thus, in this study, we evaluated the relationship between linoleic acid metabolites in the gut microbiome and subsequent revascularization after percutaneous coronary intervention (PCI), their clinical features, and stability by examining serial blood samples of patients who underwent PCI. We conducted an in vitro experimental study to assess the potential physiological effects of these metabolites to investigate the potential mechanisms of this relationship.