Compositions and method of increasing levels of apoA1 and/HDL in a subject in need thereof are provided. The compositions include one or more TLR5 agonists in a pharmaceutically acceptable carrier in an effective amount to increase the level of apoA1 and/or HDL in a subject. In a preferred embodiment, the composition is an oral formulation of the one or more TLR5 agonists. The disclosed methods include administering compositions containing the one or more TLR5 agonists to a subject in need thereof, in an effective amount to increase levels of apoA1 and/or HDL in the subject. In one preferred embodiment, the subject is at risk of developing atherosclerosis and/or coronary heart disease. In some embodiments, the subject is diagnosed as having atherosclerosis. The disclosed compositions can also be administered to subjects presenting with hyperlipidemia or hypercholesterolemia.
