Oxidized phospholipids cause changes in jejunum mucus that induce dysbiosis and systemic inflammation

Atherosclerosis: Recent developments

“…Targeting the receptor reduced atherosclerosis and boosting octanol levels increased it (Orecchioni et al, 2022). Studies have also suggested that lipid oxidation in the intestine may contribute to systemic inflammation and atherosclerosis (Mukherjee et al, 2022).…”

The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis

“…Mukherjee et al . [ 36 ■ ] compared feeding low-density lipoprotein receptor null ( Ldlr −/− ) mice a low-fat, low-cholesterol chow diet versus feeding the mice a high-fat, high-cholesterol Western diet. Surprisingly, the Western diet contained less oxidized phospholipids compared to the chow diet.…”

“…Surprisingly, the Western diet contained less oxidized phospholipids compared to the chow diet. However, on feeding the diets to the mice, the content of oxidized phospholipids (measured as immunoreactivity to E06 antibodies) in the jejunum mucus increased on the Western diet compared to the chow diet, indicating that the metabolism of the Western diet promoted the formation of oxidized phospholipids[ 36 ■ ]. On the Western diet, the mucus in the jejunum also contained higher levels of reactive oxygen species compared to mice fed the chow diet.…”

“…Gene and protein expression decreased in the jejunum of mice fed the Western diet for multiple peptides and proteins that are secreted into the mucus layer of the jejunum that act to limit bacteria numbers and limit their interaction with enterocytes. These included islet derived proteins, defensins, mucin 2, surfactant A, apoA-I, and others [ 36 ■ ]. On feeding the mice the Western diet, gene, and protein expression in jejunum decreased for interleukin 36γ, interleukin 23 and interleukin 22, which are cytokines critical for antimicrobial activity.…”

“…Consistent with these changes, the number of goblet and Paneth cells were decreased in jejunum from mice fed the Western diet. These changes provided an explanation for the decreased mucin 2 and antimicrobial levels found in the jejunum of mice fed the Western diet [ 36 ■ ]. The decreased antimicrobial defenses in the jejunum together with increased gut permeability were associated with increased levels of LPS in lymph draining from the jejunum, and in the plasma of the mice fed the Western diet [ 36 ■ ].…”