Figure 11.

Suggested model for the accumulation of PAMPs in foods and their impact on APR and RCT mediators. The enrichment of the food microbiota in proteobacterial species and their subsequent overgrowth can occur in meat and certain other food products when finely chopped and stored at or above refrigeration temperature. This leads to the accumulation of pro-inflammatory bacterial lipopeptides and lipopolysaccharides, which retain their TLR2 and TLR4-stimulating properties even after cooking has killed remaining viable bacteria (26). These TLR-stimulants may then be absorbed, particularly when intestinal barrier function is impaired, to reach the portal circulation and the liver. Although hepatocytes are insensitive to these stimulants, they may be detected by hepatic macrophages, which secrete IL-1β and other inflammatory cytokines to trigger the APR programme in hepatocytes. This results in reduced serum levels of ApoAI, which is a key mediator of RCT and atherogenesis in mice (55). Modulation of the food microbiota therefore represents a novel potential target for the modulation of systemic inflammatory markers and cholesterol metabolism.