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

Abstract

<jats:p>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.</jats:p>

The Role of Gut Microbiota in Tumor Immunotherapy

“…However, when the internal and external environment of the body changes, the homeostasis of the intestinal microbiota will be destroyed, causing imbalance of the intestinal microbiota. The imbalanced intestinal microbiota will inhibit the immune system to promote the occurrence and development of tumors [ 40 – 42 ]. Microbial disorders can promote chronic inflammation and early T cell failure by overstimulating CD8 T cells, thereby reducing antitumor immunity, resulting in colon tumor susceptibility [ 43 ].…”

Molecular Targets of Ferroptosis in Hepatocellular Carcinoma

“… 42 Understanding how immunonutrient agonists are linked to a high-fat diet, the immune system, and the microbial balance of the gut microbiota is essential for understanding the etiology of HCC. 43 In addition to affecting the changes between PUFAs, monounsaturated fatty acids and iron homeostasis, nutritional agonists such as quinoa and salvia can also mediate immune regulation against HCC through innate immunity that affects the enterohepatic circulation. 43 This also inspired us to improve the antitumor effect through diet.…”

“… 43 In addition to affecting the changes between PUFAs, monounsaturated fatty acids and iron homeostasis, nutritional agonists such as quinoa and salvia can also mediate immune regulation against HCC through innate immunity that affects the enterohepatic circulation. 43 This also inspired us to improve the antitumor effect through diet.…”

NOD1-Targeted Immunonutrition Approaches: On the Way from Disease to Health

“…However, this perspective based on the essentiality of nutrients or their biochemical role in supporting the function and activity of the immune system is experiencing significant changes toward a more molecular-targeted influence on immunity. For example, the effects derived from the interaction of certain nutrients (i.e., serine-type protease inhibitors) with the innate immune “Toll-like” receptor (TLR)-4 [ 9 , 10 ] or the role and extent that dietary modulation of this receptor can determine selective functional differentiation response(s) of innate immune mediators are receiving increasing interest. This point of view is aligned with the life sciences-based Process for the Assessment of Scientific Support for Claims on Foods (PASSCLAIM) that was coordinated by the Institute of Life Sciences (ILSI) Europe [ 11 ].…”

“…Fat-enriched diets are well-known drivers of metabolic syndrome and cardiovascular diseases [ 50 , 56 ]. In this context, the administration of immunonutritional protease inhibitors has been shown to be effective in modulating lipid homeostasis and shaping the gut microbiota, ameliorating the severity of hepatocarcinoma under HFD [ 10 ].…”