Reduced dietary intake of pro-inflammatory Toll-like receptor stimulants favourably modifies markers of cardiometabolic risk in healthy men

Background and aims: Because pro-inflammatory stimulants of Toll-like receptor-2 and TLR-4 (pathogen-associated molecular patterns, PAMPs), are abundant in some processed foods, we explored the effects of diets enriched or depleted in these molecules on markers of cardiometabolic risk in man. Methods and results: Adherence to a low PAMP diet for 7 days reduced LDL-cholesterol (-0.69 mM, P=0.024) and abdominal circumference (-1.6 cm, P=0.001) in 11 habitual consumers of high PAMP foodstuffs, and these markers, together with leukocyte counts (+14%, P=0.017) increased significantly after 4 days consuming predominantly high PAMP foods. Change in LDL-cholesterol and leukocyte counts correlated well with change in frequency of intake of high PAMP foodstuffs per individual (r=0.540, P=0.0095 and r=0.6551, P=0.0009, respectively). In an independent group of 13 healthy men, leukocyte counts and expression of the activation marker CD11b on granulocytes and monocytes were significantly reduced after a fresh onion meal (P<0.05), but these effects were reversed by a high PAMP equivalent meal. Conclusions: A low PAMP diet is associated with reduced levels of several cardiometabolic risk factors, while a high PAMP diet reverses these effects. These findings suggest a novel potential mechanistic explanation for the observed association between processed food consumption and risk of cardiometabolic diseases. The study is registered at clinicaltrials.org (reference NCT02430064).