Chenopodium Quinoa and Salvia Hispanica Provide Immunonutritional Agonists to Ameliorate Hepatocarcinoma Severity under a High-Fat Diet

Complex interactions between immunonutritional agonist and high fat intake (HFD), the immune system and finally gut microbiota are important determinants of hepatocarcinoma (HCC) severity. The ability of immunonutritional agonists to modulate major aspects such as liver innate immunity and inflammation and alterations in major lipids profile as well as gut microbiota during HCC development is poorly understood. ¹H NMR has been employed to assess imbalances in saturated fatty acids, MUFA and PUFA, which were associated to variations in iron homeostasis. These effects were dependent on the botanical nature (Chenopodium quinoa vs. Salvia hispanica L.) of the compounds. The results showed that immunonutritional agonists' promoted resistance to hepatocarcinogenesis under pro-tumorigenic inflammation reflected, at a different extent, in increased proportions of F4/80⁺ cells in injured livers as well as positive trends of accumulated immune mediators (CD68/CD206 ratio) in intestinal tissue. Administration of all immunonutritional agonists caused similar variations of fecal microbiota, towards a lower obesity-inducing potential than animals only fed a HFD. Modulation of Firmicutes to Bacteroidetes contents restored the induction of microbial metabolites to improve epithelial barrier function, showing an association with liver saturated fatty acids and the MUFA and PUFA fractions. Collectively, these data provide novel findings supporting beneficial immunometabolic effects targeting hepatocarcinogenesis, influencing innate immunity within the gut-liver axis, and providing novel insights into their immunomodulatory activity.

Keywords: hepatocarcinoma; macrophages; microbiota; myeloid cells; protease inhibitors.