Tryptophan (Trp) is one of the nine essential amino acids supplied by the diet, whose metabolism appears as a key metabolic gatekeeper of intestinal homeostasis, although its systemic effects, particularly on atherosclerosis, remain unknown. The inventors show that the high-fat diet (HFD) but not the high-cholesterol diet (HCD) increases intestinal indoleamine 2, 3-dioxygenase 1 (IDO) activity, the main enzyme involved in Trp catabolism in the gut, which shifts intestinal Trp metabolism from microbiota-produced indole metabolites and serotonin or 5-hydroxytryptamine (5-HT) production towards Kynurenine production. Most importantly the inventors showed that inhibition of tryptophan hydroxylase 1 (TpH1), markedly reduces intestinal 5-HT production and alleviates atherosclerosis as well as plaque inflammation. Accordingly, the present invention relates to the use of tryptophan hydroxylase 1 (TpH1) inhibitors for the treatment of atherosclerosis.