The Mediterranean diet as a healthy dietary model and its impact on the immune system and intestinal microbiota

The Mediterranean diet as a healthy dietary model and its impact on the immune system and intestinal microbiota

Main Article Content

Patricio Salazar
Adriana Pedreañez

Abstract

The relationship between nutrition and immunity is very complex, because each phase of the immune response can be affected by the lack of essential nutrients such as vitamins and minerals. In addition, it has been described that the most prevalent non-communicable diseases worldwide, such as metabolic syndrome, diabetes mellitus, cardiovascular diseases and cancer, underlie the activation of inflammatory mechanisms, which can compromise immune functions, often caused or accompanied by alterations in nutritional patterns and intestinal microbiota. In this context, it is clear that diet is a key modulator of the immune system and much interest is emerging in the area of nutrition as a means of treatment and prevention. The Mediterranean diet has been widely described as positively influencing and is proposed not only as a potential tool in the clinical management of different diseases, but also for global health promotion. Therefore, the aim of this review is to address the current knowledge on the regulatory role of the nutritional components present in the Mediterranean diet on the immune system and the intestinal microbiota.

References

Agrawal, S., Agrawal, A., & Said, H. M. (2016). Biotin deficiency enhances the inflammatory response of human dendritic cells. American journal of physiology. Cell physiology, 311(3), C386–C391. https://doi.org/10.1152/ajpcell.00141.2016

Aitoro, R., Paparo, L., Amoroso, A., Di Costanzo, M., Cosenza, L., Granata, V., Di Scala, C., Nocerino, R., Trinchese, G., Montella, M., Ercolini, D., & Berni Canani, R. (2017). Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy. Nutrients, 9(7), 672. https://doi.org/10.3390/nu9070672

Akimbekov, N. S., Digel, I., Sherelkhan, D. K., Lutfor, A. B., & Razzaque, M. S. (2020). Vitamin D and the Host-Gut Microbiome: A Brief Overview. Acta histochemica et cytochemica, 53(3), 33–42. https://doi.org/10.1267/ahc.20011

Aleixandre, A., & Miguel, M. (2016). Dietary fiber and blood pressure control. Food & function, 7(4), 1864–1871. https://doi.org/10.1039/c5fo00950b

Avery, J. C., & Hoffmann, P. R. (2018). Selenium, Selenoproteins, and Immunity. Nutrients, 10(9), 1203. https://doi.org/10.3390/nu10091203

Barrea, L., Muscogiuri, G., Frias-Toral, E., Laudisio, D., Pugliese, G., Castellucci, B., Garcia-Velasquez, E., Savastano, S., & Colao, A. (2021). Nutrition and immune system: from the Mediterranean diet to dietary supplementary through the microbiota. Critical reviews in food science and nutrition, 61(18), 3066–3090. https://doi.org/10.1080/10408398.2020.1792826

Biesalski H. K. (2016). Nutrition meets the microbiome: micronutrients and the microbiota. Annals of the New York Academy of Sciences, 1372(1), 53–64. https://doi.org/10.1111/nyas.13145

Bifulco M. (2015). Mediterranean diet: the missing link between gut microbiota and inflammatory diseases. European journal of clinical nutrition, 69(9), 1078. https://doi.org/10.1038/ejcn.2015.81

Bird R. P. (2018). The Emerging Role of Vitamin B6 in Inflammation and Carcinogenesis. Advances in food and nutrition research, 83, 151–194. https://doi.org/10.1016/bs.afnr.2017.11.004

Bird, J. K., Raederstorff, D., Weber, P., & Steinert, R. E. (2017). Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota. Advances in nutrition (Bethesda, Md.), 8(6), 839–849. https://doi.org/10.3945/an.117.016568

Burr, A. H. P., Bhattacharjee, A., & Hand, T. W. (2020). Nutritional Modulation of the Microbiome and Immune Response. Journal of immunology (Baltimore, Md. : 1950), 205(6), 1479–1487. https://doi.org/10.4049/jimmunol.2000419

Calder P. C. (2020). Nutrition, immunity and COVID-19. BMJ nutrition, prevention & health, 3(1), 74–92. https://doi.org/10.1136/bmjnph-2020-000085

Cantorna, M. T., Snyder, L., & Arora, J. (2019). Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Critical reviews in biochemistry and molecular biology, 54(2), 184–192. https://doi.org/10.1080/10409238.2019.1611734

Cariello, M., Contursi, A., Gadaleta, R. M., Piccinin, E., De Santis, S., Piglionica, M., Spaziante, A. F., Sabbà, C., Villani, G., & Moschetta, A. (2020). Extra-Virgin Olive Oil from Apulian Cultivars and Intestinal Inflammation. Nutrients, 12(4), 1084. https://doi.org/10.3390/nu12041084

Carr, A. C., & Maggini, S. (2017). Vitamin C and Immune Function. Nutrients, 9(11), 1211. https://doi.org/10.3390/nu9111211

Chaplin, A., Carpéné, C., & Mercader, J. (2018). Resveratrol, Metabolic Syndrome, and Gut Microbiota. Nutrients, 10(11), 1651. https://doi.org/10.3390/nu10111651

Chassard, C., & Lacroix, C. (2013). Carbohydrates and the human gut microbiota. Current opinion in clinical nutrition and metabolic care, 16(4), 453–460. https://doi.org/10.1097/MCO.0b013e3283619e63

Choi, Y., Lee, S., Kim, S., Lee, J., Ha, J., Oh, H., Lee, Y., Kim, Y., & Yoon, Y. (2020). Vitamin E (α-tocopherol) consumption influences gut microbiota composition. International journal of food sciences and nutrition, 71(2), 221–225. https://doi.org/10.1080/09637486.2019.1639637

Ciecierska, A., Drywień, M. E., Hamulka, J., & Sadkowski, T. (2019). Nutraceutical functions of betaglucans in human nutrition. Roczniki Panstwowego Zakladu Higieny, 70(4), 315–324. https://doi.org/10.32394/rpzh.2019.0082

Colica, C., Di Renzo, L., Trombetta, D., Smeriglio, A., Bernardini, S., Cioccoloni, G., Costa de Miranda, R., Gualtieri, P., Sinibaldi Salimei, P., & De Lorenzo, A. (2017). Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial. Oxidative medicine and cellular longevity, 2017, 2473495. https://doi.org/10.1155/2017/2473495

Cordain, L., Eaton, S. B., Sebastian, A., Mann, N., Lindeberg, S., Watkins, B. A., O’Keefe, J. H., & Brand-Miller, J. (2005). Origins and evolution of the Western diet: health implications for the 21st century. The American journal of clinical nutrition, 81(2), 341–354. https://doi.org/10.1093/ajcn.81.2.341

Costantini, L., Molinari, R., Farinon, B., & Merendino, N. (2017). Impact of Omega-3 Fatty Acids on the Gut Microbiota. International journal of molecular sciences, 18(12), 2645. https://doi.org/10.3390/ijms18122645

Czarnewski, P., Das, S., Parigi, S. M., & Villablanca, E. J. (2017). Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity. Nutrients, 9(1), 68. https://doi.org/10.3390/nu9010068

de Medeiros, P. H. Q. S., Pinto, D. V., de Almeida, J. Z., Rêgo, J. M. C., Rodrigues, F. A. P., Lima, A. Â. M., Bolick, D. T., Guerrant, R. L., & Oriá, R. B. (2018). Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children. Nutrients, 10(9), 1128. https://doi.org/10.3390/nu10091128

Dehghan, P., Gargari, B. P., Jafar-Abadi, M. A., & Aliasgharzadeh, A. (2014). Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomizedcontrolled clinical trial. International journal of food sciences and nutrition, 65(1), 117–123. https://doi.org/10.3109/09637486.2013.836738

Dhar, D., & Mohanty, A. (2020). Gut microbiota and Covid-19- possible link and implications. Virus research, 285, 198018. https://doi.org/10.1016/j.virusres.2020.198018

DiNicolantonio, J. J., & O’Keefe, J. H. (2018). Importance of maintaining a low omega-6/omega-3 ratio for reducing inflammation. Open heart, 5(2), e000946. https://doi.org/10.1136/openhrt-2018-000946

Elahi, A., Sabui, S., Narasappa, N. N., Agrawal, S., Lambrecht, N. W., Agrawal, A., & Said, H. M. (2018). Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. Journal of immunology (Baltimore, Md. : 1950), 200(8), 2563–2570. https://doi.org/10.4049/jimmunol.1701200

Elmadfa, I., & Meyer, A. L. (2019). The Role of the Status of Selected Micronutrients in Shaping the Immune Function. Endocrine, metabolic & immune disorders drug targets, 19(8), 1100–1115. https://doi.org/10.2174/1871530319666190529101816

Endale, M., Park, S. C., Kim, S., Kim, S. H., Yang, Y., Cho, J. Y., & Rhee, M. H. (2013). Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-κB-induced inflammatory mediators production in RAW 264.7 cells. Immunobiology, 218(12), 1452–1467. https://doi.org/10.1016/j.imbio.2013.04.019

Esposito, K., Maiorino, M. I., Bellastella, G., Panagiotakos, D. B., & Giugliano, D. (2017). Mediterranean diet for type 2 diabetes: cardiometabolic benefits. Endocrine, 56(1), 27–32. https://doi.org/10.1007/s12020-016-1018-2

Farràs, M., Martinez-Gili, L., Portune, K., Arranz, S., Frost, G., Tondo, M., & Blanco-Vaca, F. (2020). Modulation of the Gut Microbiota by Olive Oil Phenolic Compounds: Implications for Lipid Metabolism, Immune System, and Obesity. Nutrients, 12(8), 2200. https://doi.org/10.3390/nu12082200

Garcia-Mantrana, I., Selma-Royo, M., Alcantara, C., & Collado, M. C. (2018). Shifts on Gut Microbiota Associated to Mediterranean Diet Adherence and Specific Dietary Intakes on General Adult Population. Frontiers in microbiology, 9, 890. https://doi.org/10.3389/fmicb.2018.00890

Gombart, A. F., Pierre, A., & Maggini, S. (2020). A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients, 12(1), 236. https://doi.org/10.3390/nu12010236

Hoffmann P. R. (2007). Mechanisms by which selenium influences immune responses. Archivum immunologiae et therapiae experimentalis, 55(5), 289–297. https://doi.org/10.1007/s00005-007-0036-4

Hoffmann, P. R., & Berry, M. J. (2008). The influence of selenium on immune responses. Molecular nutrition & food research, 52(11), 1273–1280. https://doi.org/10.1002/mnfr.200700330

Hojyo, S., & Fukada, T. (2016). Roles of Zinc Signaling in the Immune System. Journal of immunology research, 2016, 6762343. https://doi.org/10.1155/2016/6762343

Innes, J. K., & Calder, P. C. (2018). Omega-6 fatty acids and inflammation. Prostaglandins, leukotrienes, and essential fatty acids, 132, 41–48. https://doi.org/10.1016/j.plefa.2018.03.004

Jayachandran, M., Chen, J., Chung, S. S. M., & Xu, B. (2018). A critical review on the impacts of β-glucans on gut microbiota and human health. The Journal of nutritional biochemistry, 61, 101–110. https://doi.org/10.1016/j.jnutbio.2018.06.010

Jimenez-Lopez, C., Carpena, M., Lourenço-Lopes, C., Gallardo-Gomez, M., Lorenzo, J. M., Barba, F. J., Prieto, M. A., & Simal-Gandara, J. (2020). Bioactive Compounds and Quality of Extra Virgin Olive Oil. Foods (Basel, Switzerland), 9(8), 1014. https://doi.org/10.3390/foods9081014

Karunaratne, T. B., Okereke, C., Seamon, M., Purohit, S., Wakade, C., & Sharma, A. (2020). Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson’s Disease. Nutrients, 13(1), 28. https://doi.org/10.3390/nu13010028

Kasaikina, M. V., Kravtsova, M. A., Lee, B. C., Seravalli, J., Peterson, D. A., Walter, J., Legge, R., Benson, A. K., Hatfield, D. L., & Gladyshev, V. N. (2011). Dietary selenium affects host selenoproteome expression by influencing the gut microbiota. FASEB journal : official publication

of the Federation of American Societies for Experimental Biology, 25(7), 2492–2499. https://doi.org/10.1096/fj.11-181990

Kawashima H. (2019). Intake of arachidonic acid-containing lipids in adult humans: dietary surveys and clinical trials. Lipids in health and disease, 18(1), 101. https://doi.org/10.1186/s12944-019-1039-y

Keys, A., Menotti, A., Karvonen, M. J., Aravanis, C., Blackburn, H., Buzina, R., Djordjevic, B. S., Dontas, A. S., Fidanza, F., & Keys, M. H. (1986). The diet and 15-year death rate in the seven countries study. American journal of epidemiology, 124(6), 903–915. https://doi.org/10.1093/oxfordjournals.aje.a114480

Kim, H. S., Hong, J. T., Kim, Y., & Han, S. B. (2011). Stimulatory Effect of β-glucans on Immune Cells. Immune network, 11(4), 191–195. https://doi.org/10.4110/in.2011.11.4.191

Kobori, M., Takahashi, Y., Sakurai, M., Akimoto, Y., Tsushida, T., Oike, H., & Ippoushi, K. (2016). Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet-induced obese mice. Molecular nutrition & food research, 60(2), 300–312. https://doi.org/10.1002/mnfr.201500595

Koudoufio, M., Desjardins, Y., Feldman, F., Spahis, S., Delvin, E., & Levy, E. (2020). Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?. Antioxidants (Basel, Switzerland), 9(10), 982. https://doi.org/10.3390/antiox9100982

Krznarić, Ž., Vranešić Bender, D., & Meštrović, T. (2019). The Mediterranean diet and its association with selected gut bacteria. Current opinion in clinical nutrition and metabolic care, 22(5), 401–406. https://doi.org/10.1097/MCO.0000000000000587

Kumar Singh, A., Cabral, C., Kumar, R., Ganguly, R., Kumar Rana, H., Gupta, A., Rosaria Lauro, M., Carbone, C., Reis, F., & Pandey, A. K. (2019). Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency. Nutrients, 11(9), 2216. https://doi.org/10.3390/nu11092216

Kunisawa, J., & Kiyono, H. (2013). Vitamin-mediated regulation of intestinal immunity. Frontiers in immunology, 4, 189. https://doi.org/10.3389/fimmu.2013.00189

Kuroishi T. (2015). Regulation of immunological and inflammatory functions by biotin. Canadian journal of physiology and pharmacology, 93(12), 1091–1096. https://doi.org/10.1139/cjpp2014-0460

Lee, A. H., & Dixit, V. D. (2020). Dietary Regulation of Immunity. Immunity, 53(3), 510–523. https://doi.org/10.1016/j.immuni.2020.08.013

Lewis, J. D., Chen, E. Z., Baldassano, R. N., Otley, A. R., Griffiths, A. M., Lee, D., Bittinger, K., Bailey, A., Friedman, E. S., Hoffmann, C., Albenberg, L., Sinha, R., Compher, C., Gilroy, E., Nessel, L., Grant, A., Chehoud, C., Li, H., Wu, G. D., & Bushman, F. D. (2015). Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease. Cell host & microbe, 18(4), 489–500. https://doi.org/10.1016/j.chom.2015.09.008

Li, L., Feng, L., Jiang, W. D., Jiang, J., Wu, P., Kuang, S. Y., Tang, L., Tang, W. N., Zhang, Y. A., Zhou, X. Q., & Liu, Y. (2015). Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella). Fish & shellfish immunology, 45(2), 399–413. https://doi.org/10.1016/j.fsi.2015.04.030

Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M. T., Wang, S., Liu, H., & Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8(3), 167. https://doi.org/10.3390/nu8030167

Liu, F., Li, P., Chen, M., Luo, Y., Prabhakar, M., Zheng, H., He, Y., Qi, Q., Long, H., Zhang, Y., Sheng, H., & Zhou, H. (2017). Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population. Scientific reports, 7(1), 11789. https://doi.org/10.1038/s41598-017-10722-2

Luisi, M. L. E., Lucarini, L., Biffi, B., Rafanelli, E., Pietramellara, G., Durante, M., Vidali, S., Provensi, G., Madiai, S., Gheri, C. F., Masini, E., & Ceccherini, M. T. (2019). Effect of Mediterranean Diet Enriched in High Quality Extra Virgin Olive Oil on Oxidative Stress, Inflammation and Gut Microbiota in Obese and Normal Weight Adult Subjects. Frontiers in pharmacology, 10, 1366. https://doi.org/10.3389/fphar.2019.01366

Maares, M., & Haase, H. (2016). Zinc and immunity: An essential interrelation. Archives of biochemistry and biophysics, 611, 58–65. https://doi.org/10.1016/j.abb.2016.03.022

Mahajan, R., Attri, S., Mehta, V., Udayabanu, M., & Goel, G. (2018). Microbe-bio-Chemical Insight: Reviewing Interactions between Dietary Polyphenols and Gut Microbiota. Mini reviews in medicinal chemistry, 18(15), 1253–1264. https://doi.org/10.2174/1389557517666170208142817

Malaguarnera L. (2019). Influence of Resveratrol on the Immune Response. Nutrients, 11(5), 946. https://doi.org/10.3390/nu11050946

Man, A. W. C., Zhou, Y., Xia, N., & Li, H. (2020). Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism. Nutrients, 12(10), 3054. https://doi.org/10.3390/nu12103054

Marcelino, G., Hiane, P. A., Freitas, K. C., Santana, L. F., Pott, A., Donadon, J. R., & Guimarães, R. C. A. (2019). Effects of Olive Oil and Its Minor Components on Cardiovascular Diseases, Inflammation, and Gut Microbiota. Nutrients, 11(8), 1826. https://doi.org/10.3390/nu11081826

Mazzocchi, A., Leone, L., Agostoni, C., & Pali-Schöll, I. (2019). The Secrets of the Mediterranean Diet. Does [Only] Olive Oil Matter?. Nutrients, 11(12), 2941. https://doi.org/10.3390/nu11122941

Merra, G., Noce, A., Marrone, G., Cintoni, M., Tarsitano, M. G., Capacci, A., & De Lorenzo, A. (2020). Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients, 13(1), 7. https://doi.org/10.3390/nu13010007

Merra, G., Noce, A., Marrone, G., Cintoni, M., Tarsitano, M. G., Capacci, A., & De Lorenzo, A. (2020). Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients, 13(1), 7. https://doi.org/10.3390/nu13010007

Mikkelsen, K., & Apostolopoulos, V. (2018). B Vitamins and Ageing. Sub-cellular biochemistry, 90, 451–470. https://doi.org/10.1007/978-981-13-2835-0_15

Mithul Aravind, S., Wichienchot, S., Tsao, R., Ramakrishnan, S., & Chakkaravarthi, S. (2021). Role of dietary polyphenols on gut microbiota, their metabolites and health benefits. Food research international (Ottawa, Ont.), 142, 110189. https://doi.org/10.1016/j.foodres.2021.110189

Montserrat-de la Paz, S., Naranjo, M. C., Lopez, S., Abia, R., Muriana, F. J. G., & Bermudez, B. (2017). Niacin and its metabolites as master regulators of macrophage activation. The Journal of nutritional biochemistry, 39, 40–47. https://doi.org/10.1016/j.jnutbio.2016.09.008

Mora, J. R., Iwata, M., & von Andrian, U. H. (2008). Vitamin effects on the immune system: vitamins A and D take centre stage. Nature reviews. Immunology, 8(9), 685–698. https://doi.org/10.1038/nri2378

Nelson, J. E., Roth, C. L., Wilson, L. A., Yates, K. P., Aouizerat, B., Morgan-Stevenson, V., Whalen, E., Hoofnagle, A., Mason, M., Gersuk, V., Yeh, M. M., & Kowdley, K. V. (2016). Vitamin D Deficiency Is Associated With Increased Risk of Non-alcoholic Steatohepatitis in Adults With

Non-alcoholic Fatty Liver Disease: Possible Role for MAPK and NF-κB?. The American journal of gastroenterology, 111(6), 852–863. https://doi.org/10.1038/ajg.2016.51

Nishida, A., Inoue, R., Inatomi, O., Bamba, S., Naito, Y., & Andoh, A. (2018). Gut microbiota in the pathogenesis of inflammatory bowel disease. Clinical journal of gastroenterology, 11(1), 1–10. https://doi.org/10.1007/s12328-017-0813-5

Ortega, M. A., Fraile-Martínez, O., Naya, I., García-Honduvilla, N., Álvarez-Mon, M., Buján, J., Asúnsolo, Á., & de la Torre, B. (2020). Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications. Nutrients, 12(9), 2749. https://doi.org/10.3390/nu12092749

Ozdal, T., Sela, D. A., Xiao, J., Boyacioglu, D., Chen, F., & Capanoglu, E. (2016). The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility. Nutrients, 8(2), 78. https://doi.org/10.3390/nu8020078

Padayatty, S. J., & Levine, M. (2016). Vitamin C: the known and the unknown and Goldilocks. Oral diseases, 22(6), 463–493. https://doi.org/10.1111/odi.12446

Park, S., Kang, S., & Sol Kim, D. (2022). Folate and vitamin B-12 deficiencies additively impaire memory function and disturb the gut microbiota in amyloid-β infused rats. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, 92(3-4), 169–181. https://doi.org/10.1024/0300-9831/a000624

Parmanand, B. A., Kellingray, L., Le Gall, G., Basit, A. W., Fairweather-Tait, S., & Narbad, A. (2019). A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study. The Journal of nutritional biochemistry, 67, 20–27. https://doi.org/10.1016/j.jnutbio.2019.01.010

Pecora, F., Persico, F., Argentiero, A., Neglia, C., & Esposito, S. (2020). The Role of Micronutrients in Support of the Immune Response against Viral Infections. Nutrients, 12(10), 3198. https://doi.org/10.3390/nu12103198

Pedreáñez, AB. ; Mosquera-Sulbarán, J; Muñóz, N ; Tene, D; Robalino, J (2022). Vitamin D and immune response against severe acute respiratory syndrome coronavirus 2 in older adults: does it really work? Reviews and Research in Medical Microbiology 33(3):p 129-138. https://doi.org/10.1097/MRM.0000000000000307

Perrone, M. A., Gualtieri, P., Gratteri, S., Ali, W., Sergi, D., Muscoli, S., Cammarano, A., Bernardini, S., Di Renzo, L., & Romeo, F. (2019). Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: a nutrigenomic approach for cardiovascular prevention. Journal of cardiovascular medicine (Hagerstown, Md.), 20(7), 419–426. https://doi.org/10.2459/JCM.0000000000000816

Piccinin, E., Cariello, M., De Santis, S., Ducheix, S., Sabbà, C., Ntambi, J. M., & Moschetta, A. (2019). Role of Oleic Acid in the Gut-Liver Axis: From Diet to the Regulation of Its Synthesis via StearoylCoA Desaturase 1 (SCD1). Nutrients, 11(10), 2283. https://doi.org/10.3390/nu11102283

Porter, K., Hoey, L., Hughes, C. F., Ward, M., & McNulty, H. (2016). Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing. Nutrients, 8(11), 725. https://doi.org/10.3390/nu8110725

Prescott S. L. (2016). Early Nutrition as a Major Determinant of ‘Immune Health’: Implications for Allergy, Obesity and Other Noncommunicable Diseases. Nestle Nutrition Institute workshop series, 85, 1–17. https://doi.org/10.1159/000439477

Putnam, E. E., & Goodman, A. L. (2020). B vitamin acquisition by gut commensal bacteria. PLoS pathogens, 16(1), e1008208. https://doi.org/10.1371/journal.ppat.1008208

Qian, B., Shen, S., Zhang, J., & Jing, P. (2017). Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations. Journal of immunology research, 2017, 2197975. https://doi.org/10.1155/2017/2197975

Rebello, C. J., O’Neil, C. E., & Greenway, F. L. (2016). Dietary fiber and satiety: the effects of oats on satiety. Nutrition reviews, 74(2), 131–147. https://doi.org/10.1093/nutrit/nuv063

Rodionov, D. A., Arzamasov, A. A., Khoroshkin, M. S., Iablokov, S. N., Leyn, S. A., Peterson, S. N., Novichkov, P. S., & Osterman, A. L. (2019). Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome. Frontiers in microbiology, 10, 1316. https://doi.org/10.3389/fmicb.2019.01316

Roshanravan, N., Alamdari, N. M., Jafarabadi, M. A., Mohammadi, A., Shabestari, B. R., Nasirzadeh, N., Asghari, S., Mansoori, B., Akbarzadeh, M., Ghavami, A., Ghaffari, S., & Ostadrahimi, A. (2020). Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Cytokine, 131, 155101. https://doi.org/10.1016/j.cyto.2020.155101

Saini, R. K., & Keum, Y. S. (2018). Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - A review. Life sciences, 203, 255–267. https://doi.org/10.1016/j.lfs.2018.04.049

Schröder, L., Kaiser, S., Flemer, B., Hamm, J., Hinrichsen, F., Bordoni, D., Rosenstiel, P., & Sommer, F. (2020). Nutritional Targeting of the Microbiome as Potential Therapy for Malnutrition and Chronic Inflammation. Nutrients, 12(10), 3032. https://doi.org/10.3390/nu12103032

Serra-Majem, L., Román-Viñas, B., Sanchez-Villegas, A., Guasch-Ferré, M., Corella, D., & La Vecchia, C. (2019). Benefits of the Mediterranean diet: Epidemiological and molecular aspects. Molecular aspects of medicine, 67, 1–55. https://doi.org/10.1016/j.mam.2019.06.001

Shahidi, F., & Ambigaipalan, P. (2018). Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. Annual review of food science and technology, 9, 345–381. https://doi.org/10.1146/annurev-food-111317-095850

Sharma, L., & Riva, A. (2020). Intestinal Barrier Function in Health and Disease-Any role of SARSCoV-2?. Microorganisms, 8(11), 1744. https://doi.org/10.3390/microorganisms8111744

Slavin J. (2013). Fiber and prebiotics: mechanisms and health benefits. Nutrients, 5(4), 1417–1435. https://doi.org/10.3390/nu5041417

Sonnenburg, E. D., & Sonnenburg, J. L. (2014). Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell metabolism, 20(5), 779–786. https://doi.org/10.1016/j.cmet.2014.07.003

Sonnenburg, E. D., Smits, S. A., Tikhonov, M., Higginbottom, S. K., Wingreen, N. S., & Sonnenburg, J. L. (2016). Diet-induced extinctions in the gut microbiota compound over generations. Nature, 529(7585), 212–215. https://doi.org/10.1038/nature16504

Spinas, E., Saggini, A., Kritas, S. K., Cerulli, G., Caraffa, A., Antinolfi, P., Pantalone, A., Frydas, A., Tei, M., Speziali, A., Saggini, R., Pandolfi, F., & Conti, P. (2015). CROSSTALK BETWEEN VITAMIN B AND IMMUNITY. Journal of biological regulators and homeostatic agents, 29(2),

–288.

Strasser, B., Wolters, M., Weyh, C., Krüger, K., & Ticinesi, A. (2021). The Effects of Lifestyle and Diet on Gut Microbiota Composition, Inflammation and Muscle Performance in Our Aging Society. Nutrients, 13(6), 2045. https://doi.org/10.3390/nu13062045

Su, D., Nie, Y., Zhu, A., Chen, Z., Wu, P., Zhang, L., Luo, M., Sun, Q., Cai, L., Lai, Y., Xiao, Z., Duan, Z., Zheng, S., Wu, G., Hu, R., Tsukamoto, H., Lugea, A., Liu, Z., Pandol, SJ y Han, YP (2016 ). La señalización de vitamina D a través de la inducción de defensinas de células de Paneth

mantiene la microbiota intestinal y mejora los trastornos metabólicos y la esteatosis hepática en modelos animales. Fronteras en fisiología, 7, 498. https://doi.org/10.3389/fphys.2016.00498

Suwannasom, N., Kao, I., Pruß, A., Georgieva, R., & Bäumler, H. (2020). Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. International journal of molecular sciences, 21(3), 950. https://doi.org/10.3390/ijms21030950

Swamy, S. M., Rajasekaran, N. S., & Thannickal, V. J. (2016). Nuclear Factor-Erythroid-2-Related Factor 2 in Aging and Lung Fibrosis. The American journal of pathology, 186(7), 1712–1723. https://doi.org/10.1016/j.ajpath.2016.02.022

Tavintharan, S., Woon, K., Pek, L. T., Jauhar, N., Dong, X., Lim, S. C., & Sum, C. F. (2011). Niacin results in reduced monocyte adhesion in patients with type 2 diabetes mellitus. Atherosclerosis, 215(1), 176–179. https://doi.org/10.1016/j.atherosclerosis.2010.12.020

Tejera Pérez, C., Guillín Amarelle, C., Rodríguez Novo, N., Lugo Rodríguez, G., Mantiñán Gil, B., Palmeiro Carballeira, R., Pita Gutiérrez, F., Argüeso Armesto, R., Cantón Blanco, A., Botana López, M. A., Fernández López, M. T., Muñoz Leira, V., Rodeiro Marta, S., & Martínez Olmos, M. Á. (2023). Inmunonutrición, evidencias y experiencias [Immunonutrition, evidence and experiences]. Nutricion hospitalaria, 40(1), 186–199. https://doi.org/10.20960/nh.04226

Tosti, V., Bertozzi, B., & Fontana, L. (2018). Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. The journals of gerontology. Series A, Biological sciences and medical sciences, 73(3), 318–326. https://doi.org/10.1093/gerona/glx227

Traber, M. G., & Atkinson, J. (2007). Vitamin E, antioxidant and nothing more. Free radical biology & medicine, 43(1), 4–15. https://doi.org/10.1016/j.freeradbiomed.2007.03.024

Tullio, V., Gasperi, V., Catani, M. V., & Savini, I. (2020). The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers. Nutrients, 13(1), 81. https://doi.org/10.3390/nu13010081

Ueland, PM, McCann, A., Midttun, Ø. y Ulvik, A. (2017). Inflamación, vitamina B6 y vías relacionadas. Aspectos moleculares de la medicina, 53, 10–27. https://doi.org/10.1016/j.mam.2016.08.001

van Dam, B., van Hinsbergh, V. W., Stehouwer, C. D., Versteilen, A., Dekker, H., Buytenhek, R., Princen, H. M., & Schalkwijk, C. G. (2003). Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects. Cardiovascular research, 57(2), 563–571. https://doi.org/10.1016/s0008-6363(02)00699-5

van de Lagemaat, E. E., de Groot, L. C. P. G. M., & van den Heuvel, E. G. H. M. (2019). Vitamin B12 in Relation to Oxidative Stress: A Systematic Review. Nutrients, 11(2), 482. https://doi.org/10.3390/nu11020482

Venter, C., Eyerich, S., Sarin, T., & Klatt, K. C. (2020). Nutrition and the Immune System: A Complicated Tango. Nutrients, 12(3), 818. https://doi.org/10.3390/nu12030818

Verginelli, F., Aru, F., Battista, P., & Mariani-Costantini, R. (2009). Nutrigenetics in the light of human evolution. Journal of nutrigenetics and nutrigenomics, 2(2), 91–102. https://doi.org/10.1159/000228251

Wakade, C., Giri, B., Malik, A., Khodadadi, H., Morgan, J. C., Chong, R. K., & Baban, B. (2018). Niacin modulates macrophage polarization in Parkinson’s disease. Journal of neuroimmunology, 320, 76–79. https://doi.org/10.1016/j.jneuroim.2018.05.002

Wan, M. L. Y., Ling, K. H., El-Nezami, H., & Wang, M. F. (2019). Influence of functional food components on gut health. Critical reviews in food science and nutrition, 59(12), 1927–1936. https://doi.org/10.1080/10408398.2018.1433629

Wang, C., Zhang, R., Wei, X., Lv, M. y Jiang, Z. (2020). Metaloinmunología: La inmunidad controlada por iones metálicos. Avances en inmunología, 145, 187–241. https://doi.org/10.1016/bs.ai.2019.11.007

Wessels, I., Maywald, M., & Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9(12), 1286. https://doi.org/10.3390/nu9121286

Westfall, S., & Pasinetti, G. M. (2019). The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders. Frontiers in neuroscience, 13, 1196. https://doi.org/10.3389/fnins.2019.01196

Wu, W., Sun, M., Chen, F., Cao, A. T., Liu, H., Zhao, Y., Huang, X., Xiao, Y., Yao, S., Zhao, Q., Liu, Z., & Cong, Y. (2017). Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal immunology, 10(4), 946–956. https://doi.org/10.1038/mi.2016.114

Xu, C., Sun, R., Qiao, X., Xu, C., Shang, X., Niu, W., & Chao, Y. (2014). Effect of vitamin e supplementation on intestinal barrier function in rats exposed to high altitude hypoxia environment. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 18(4), 313–320. https://doi.org/10.4196/kjpp.2014.18.4.313

Zhang, Y. G., Wu, S., & Sun, J. (2013). Vitamin D, Vitamin D Receptor, and Tissue Barriers. Tissue barriers, 1(1), e23118. https://doi.org/10.4161/tisb.23118