Immunonutrition: novel modulators of effectiveness and quality of anti-tumoral responses
The unprecedented non-alcoholic fatty liver disease (NAFLD) pandemic is going to have a strong impact on future morbidity rates and a reduction in life expectancy by 5-20 years. NAFLD has become the most common liver pathology worldwide affecting an estimated 15- 30% of most populations due to a dramatic increase of risk factors such as obesity, sedentary life style and altered food supply and preferences.
Thus, 10-20% of subjects with NAFLD will have the severe variant of non-alcoholic steatohepatitis (NASH), hepatic inflammation and the development of liver fibrosis with high liver related morbidity and mortality, part of which is due to the development of hepatocellular carcinoma. Innate immune Toll-like receptor (TLR)-4 and gut microbiota has been identified as determinants for hepatocellular carcinoma promotion. While the host’s endogenous factors are difficult to influence, the environmental factors are predominant and addressable in a preventive or therapeutic intention. A clear example is the activation of intestinal innate immune responses via toll-like receptor (TLR)-4 by defined protease inhibitors present in cereals.
TLR4 activation in macrophages, central in coordinating innate immune responses, is associated to metabolic changes influencing functional differentiation and antigen presentation and, thereby, effector T cells function and activity. In this context, lipid mediator profiles change with macrophages phenotype. In the group of Molecular Immunonutrition in the Metabolic Dysfunction and anti-Tumoral Response, we have recently defined significant a different cytotoxic and immunogenic potential of protease inhibitors from wheat and ancient-Latin American grains. This contribution helps to understand the role of immunonutritional food components to enforce the development of immune-based precision intervention tools and strategies as well as innovative scientific, translational and transferable, relevant aspects to improve the production of innovative healthier products.
Therefore, this immunonutritional-based precision imprinting is an example of how to overcome the usually fragmented and compartmentalized approach to address the impact of innate immune responses in NAFLD.
Here, a better understanding and the use of immunonutritional compounds will help to reduce the socioeconomic burden and risk factors for NAFLD i.e., diabetes, obesity, and hyperlipidemia as well as the metabolic syndrome. Effective immunonutritional-based precision prevention/therapeutic strategies could also help to promote a healthier intrauterine immunity.
Thus, the use of immunonutritional-based precision tools that ameliorate/prevent NAFLD represents a new hope to help arming the clinical/scientific community with effective translational and transferable strategies targeting not only liver-related diseases, but also progress to fibrosis and hepatocellular carcinoma.
1. Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013, 28 S1:68-76
2. Dapito DH, Mencin A, Gwak GY, et al. Promotion of Hepatocellular carcinoma by intestinal microbiota and TLR4. Cancer Cell 2012, 21(4), 504-516
3. Kaliszewska A, Martinez V, Laparra M. Proinflammatory responses driven by non-gluten factors are masked when they appear associated to gliadins. Food Chem Toxicol. 2016, 95, 89-95
4. Laparra M, Díez M, Moreno FJ et al. Kojibiose ameliorates arachidic acid-mediated liver alterations in hyperglucemic rats. Br J Nutr. 2015, 114(9), 1395-402
5. Laparra M, Olivares M, Gallina O, et al. Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model. PLoS One. 2012;7(2):e30744
6. Olivares M, Laparra M, Sanz Y. Oral administration of Bifidobacterium longum CECT 7347 modulates jejunal proteome in an in vivo gliadin-induced enteropathy animal model. J Proteomics. 2012, 77:310-20