We previously reported that adding a concentrate of transgenic tomatoes expressing the
apoA-I mimetic
peptide 6F (Tg6F) to a Western diet (WD) ameliorated systemic
inflammation. To determine the mechanism(s) responsible for these observations, Ldlr-/- mice were fed chow, a WD, or WD plus Tg6F. We found that a WD altered the taxonomic composition of bacteria in jejunum mucus. For example, Akkermansia muciniphila virtually disappeared, while overall bacteria numbers and
lipopolysaccharide (LPS) levels increased. In addition, gut permeability increased, as did the content of
reactive oxygen species and oxidized
phospholipids in jejunum mucus in WD-fed mice. Moreover, gene expression in the jejunum decreased for multiple
peptides and
proteins that are secreted into the mucous layer of the jejunum that act to limit bacteria numbers and their interaction with enterocytes including
regenerating islet-derived proteins,
defensins,
mucin 2,
surfactant A, and
apoA-I. Following WD, gene expression also decreased for Il36γ, Il23, and Il22,
cytokines critical for antimicrobial activity. WD decreased expression of both Atoh1 and Gfi1, genes required for the formation of goblet and Paneth cells, and immunohistochemistry revealed decreased numbers of goblet and Paneth cells. Adding Tg6F ameliorated these WD-mediated changes. Adding oxidized
phospholipids ex vivo to the jejunum from mice fed a chow diet reproduced the changes in gene expression in vivo that occurred when the mice were fed WD and were prevented with addition of
6F peptide. We conclude that Tg6F ameliorates the WD-mediated increase in oxidized
phospholipids that cause changes in jejunum mucus, which induce
dysbiosis and systemic
inflammation.