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The edition of September of the Journal of Pediatric Gastroenterology and Nutrition (Journal of Pediatric Gastroenterology and Nutrition
, acronym in English, JPGN) brought up a topic that is currently much debated in academia: what would be the role of food in the child’s immune system?
Know more: The various effects of alcohol on the functioning of the immune system
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The role of proteins
Protein-calorie malnutrition is related to immune dysfunction and increased susceptibility to infections. It can lead to loss of lymphoid tissue and microbiome dysregulation, impairing the barrier function of the gastrointestinal tract. As infections occur, the high rates of cell proliferation and DNA replication that the intestinal epithelium needs for its proper functioning are impaired. In addition, protein deficiency impacts the functions of hematopoietic and lymphoid organs, such as the thymus, bone marrow, spleen, lymph nodes, and mucosa-associated lymphoid tissue, and compromises the function of innate and acquired immunities.
The role of proteins
Protein-calorie malnutrition is related to immune dysfunction and increased susceptibility to infections. It can lead to loss of lymphoid tissue and microbiome dysregulation, impairing the barrier function of the gastrointestinal tract. As infections occur, the high rates of cell proliferation and DNA replication that the intestinal epithelium needs for its proper functioning are impaired. In addition, protein deficiency impacts the functions of hematopoietic and lymphoid organs, such as the thymus, bone marrow, spleen, lymph nodes, and mucosa-associated lymphoid tissue, and compromises the function of innate and acquired immunities.
THE
arginine is essential for the proper functioning of the cardiovascular and immune systems and for wound healing. In the postoperative context, this amino acid is able to stimulate the response of macrophages and monocytes, in addition to being a substrate for the proper functioning of T cells. The use of parenteral nutrition enriched with arginine in patients with peritonitis was correlated with greater survival. In addition, enteral nutrition containing arginine, nucleotides and omega 3 was correlated with better functioning of the child’s immune system. Fatty acids that make up omega 3 (eicosapentaenoic and docosahexaenoic [DHA]) are able to suppress the pro-inflammatory state induced by low levels of arginine. And, apparently, arginine supplementation is related to the prevention of necrotizing enterocolitis in preterm infants. To date, there are few randomized clinical trials evaluating childhood arginine supplementation.
Better known than the previous amino acid,
glutamine also plays an important immunoregulatory role, being essential for lymphocyte proliferation, cytokine production , activation of macrophages and neutrophils. In healthy patients with a balanced diet, supplemental glutamine is not necessary. However, in the presence of catabolism or low protein intake, amino acid replacement may be required. Therefore, it is important to maintain an adequate protein intake, especially during periods of accelerated growth, such as the first years of life and puberty. Bioactive peptides also have important immunoregulatory functions. Most studies focus on proteins from dairy products, but proteins derived from vegetables and animals are also being studied. Peptides can be absorbed from the intestine, interact with macrophages, dendritic cells and B lymphocytes, influencing the production of cytokines and antibodies. 
The role of lipids
Lipids are an important energy source. Of particular importance are polyunsaturated fatty acids (polyunsaturated fatty acids – PUFAs) of high caloric density: omegas 6 and 3. Its importance in the child’s immune system is well known: both DHA and its precursor, omega 3, are correlated with modulation of adaptive and innate immune responses. DHA can inhibit the inflammatory response through some of its products such as resolvin, protectins and maresins. Type E and DA resolvins (RvD and RvE), in association with (neuro)protectin D1, are associated with the anti-inflammatory response. The latter also exhibits immunomodulatory activities. Maresins also have a strong anti-inflammatory action, similarly to RvD and RvE. For children under 2 years of age, a daily intake of DHA is recommended 100mg, in one or more meals, and 250mg in larger meals. The main sources of DHA are oily fish. However, fish rich in mercury should be avoided to avoid intoxication. Another type of fatty acid that can also modulate immune function is conjugated linoleic acid (conjugated linoleic acid – CLA) . Unlike the others mentioned, it is a trans fat (unsaturated), that is, not produced by the human body. It is generated in the intestinal lumen of ruminant animals and is present in cow’s milk, dairy products and also in breast milk. CLA acts in the production of cytokines, nitric oxide and eicosanoids (prostaglandins, leukotrienes) and inhibits the expression of eosinophilic cationic protein and receptors activated by peroxisome proliferators, both involved in the cellular inflammatory cascade. Furthermore, its protective effect on the development of atopic diseases in babies is well demonstrated. The role of carbohydrates
Prebiotics are non-digestible carbohydrates that influence the activity and composition of the microbiota. Many studies show that the consumption of a wide variety of carbohydrates with prebiotic activity increases the number of bacteria beneficial to human health. Carbohydrates with potential prebiotic activity are found in edible plants.Prebiotics have beneficial effects on the functioning of the immune system. Although the exact mechanism through which this occurs is not well understood, there are some hypotheses:
Increased production of short-chain fatty acids, such as propionic acid, capable of acting on hepatic lipogenic enzymes ;
Increased production of short-chain fatty acids, such as butyric acid, which acts as a genetic transcription factor;
Modulation of mucin production;
Increase in the number of lymphocytes and/or leukocytes in the mucosa-associated lymphoid tissue ([DHA] gut-associated lymphoid tissue
– GALT) and in the peripheral blood; Stimulation of phagocytic function of macrophages by increased secretion of immunoglobulin A by GALT. 
Micronutrients Vitamins
Vitamins and minerals play a crucial role in both adaptive and innate immune responses. Sufficient intakes to generate adequate serum levels are essential to reduce susceptibility to infections.
Vitamin A: increases mucin secretion, aiding in the function of the mucosal barrier. It also regulates the differentiation, maturation and function of macrophages and neutrophils; Vitamin B6: acts in production of interleukin-2; Vitamin B9 (folic acid) and B12: Vitamin B12 plays an important role in the cytotoxic immune response by stimulating cells Natural Killer (NK) and CD8+. Vitamin B12 deficiency leads to the accumulation of tetrahydrofolic acid in its methylated form, which can be harmful. Keeping the amount of the two vitamins in balance is, therefore, extremely important for the immune response. Blood levels of vitamin B12 above 221 pmol/L (> 300ng/L or pg/mL) are considered normal;Vitamin C: acts on the growth and function of cells involved in innate and adaptive immunity, phagocytosis and microbial death, antibody production and epithelial barrier function ; Vitamin D: increases production by monocytes and macrophages of antimicrobial peptides such as cathelicidin and βdefensin. Promotes autophagy, as well as the chemotactic and phagocytic abilities of the cells of the innate immune system. In addition, it acts on the adaptive immune system, with a general inhibitory effect on both T cells and B cells and also on the innate, by inhibiting the differentiation and maturation of dendritic cells, generating a more tolerogenic state. The term hypovitaminosis D refers to serum levels of 25(OH)D Vitamin E: is involved in phagocytosis, proliferation and differentiation of T cells and antibody production. It is an important scavenger of reactive oxygen species, particularly harmful to polyunsaturated fatty acids present in membrane phospholipids and blood lipoproteins. During immune reactions, vitamin E protects cells and functional components, such as proteins and fatty acids, from damage caused by defense mechanisms against pathogens. Minerals
Zinc: the development and functioning of innate immunity are closely related to zinc homeostasis. When this mineral is deficient, the function of macrophages (phagocytosis, intracellular death), T and B cells and the production of cytokines are compromised. Zinc regulates the release of pro-inflammatory cytokines (interleukins 1 and 6 [IL-1 e IL-6] and tumor necrosis factor alpha [tumor necrosis factor alpha – TNF-α) by cells of innate immunity. Additionally, zinc deficiency is associated with diarrhea and respiratory infections. Zinc has been correlated with prevention of respiratory infections in children aged 2–60 months in low- and middle-income countries. And, in an Israeli study involving children aged 6 months to 3 years, zinc supplementation reduced the duration and severity of respiratory infections. The main dietary sources of zinc are plant foods such as grains, nuts and animal foods such as red meat, fish and cheese; Copper: has essential action on immunity mediated by cells and in the formation of antibodies. It acts on macrophages, helper T cells, B cells, neutrophils and NK cells . 
Children who suffer from disabilities copper are more susceptible to bacterial infections, especially respiratory ones. Liver and fish are rich in copper; small amounts are found in aged cheeses. Nuts and cocoa are an alternative vegan source;Selenium: has essential anti-inflammatory effects, exerted through the mitogen-activated protein kinase (mitogen-activated protein kinase – MAPK), nuclear factor kappa B (nuclear factor-κB – NF-kB) and the regulation of pro-inflammatory mediators dependent on the peroxisome proliferator activated receptor (peroxisome proliferator-activated receptor – PPAR). Selenium deficiency has been associated with sepsis in intensive care patients. Premature babies are prone to low levels and supplementation decreases the risk of nosocomial sepsis. Selenium can be found in liver, meat and fish. Low selenium intake is found in many areas of Europe due to the low levels found in the soil; Iron: the proliferation and maturation of various cells of the immune system are dependent on iron, particularly lymphocytes. Intracellular iron participates in the release of reactive oxygen species and the production of antimicrobial peptides by macrophages. In addition, iron supplementation in patients with deficiency has been correlated with increased TNF-a, IL-6, and IL-10 mRNA in peripheral blood mononuclear cells. Iron deficiency is common and results in iron deficiency anemia, associated with increased susceptibility to infections, fatigue, metabolic stress, reduced cognitive functions and impaired growth. Iron deficiency is diagnosed when serum ferritin levels are below 12mg/L for children under 5 years of age, or below 15mg/L for those 5 years and older. In a Chinese study, combined iron and vitamin A supplementation reduced the incidence of diarrhea and respiratory illness in Chinese preschool children. Foods contain heme iron found in meat and non-heme iron found in vegetables and dairy products. The latter is less absorbed. Consumption of vitamin C together with iron improves its absorption. Meat, egg, grains, vegetables and some vegetables are rich in iron.
Read too: Recommendations on the vegetarian diet for children and adolescents
The role of lipids
- Increased production of short-chain fatty acids, such as propionic acid, capable of acting on hepatic lipogenic enzymes ;
MicronutrientsVitamins
Vitamin C: acts on the growth and function of cells involved in innate and adaptive immunity, phagocytosis and microbial death, antibody production and epithelial barrier function ; Vitamin D: increases production by monocytes and macrophages of antimicrobial peptides such as cathelicidin and βdefensin. Promotes autophagy, as well as the chemotactic and phagocytic abilities of the cells of the innate immune system. In addition, it acts on the adaptive immune system, with a general inhibitory effect on both T cells and B cells and also on the innate, by inhibiting the differentiation and maturation of dendritic cells, generating a more tolerogenic state. The term hypovitaminosis D refers to serum levels of 25(OH)D Vitamin E: is involved in phagocytosis, proliferation and differentiation of T cells and antibody production. It is an important scavenger of reactive oxygen species, particularly harmful to polyunsaturated fatty acids present in membrane phospholipids and blood lipoproteins. During immune reactions, vitamin E protects cells and functional components, such as proteins and fatty acids, from damage caused by defense mechanisms against pathogens. Minerals – NF-kB) and the regulation of pro-inflammatory mediators dependent on the peroxisome proliferator activated receptor (peroxisome proliferator-activated receptor – PPAR). Selenium deficiency has been associated with sepsis in intensive care patients. Premature babies are prone to low levels and supplementation decreases the risk of nosocomial sepsis. Selenium can be found in liver, meat and fish. Low selenium intake is found in many areas of Europe due to the low levels found in the soil; Iron: the proliferation and maturation of various cells of the immune system are dependent on iron, particularly lymphocytes. Intracellular iron participates in the release of reactive oxygen species and the production of antimicrobial peptides by macrophages. In addition, iron supplementation in patients with deficiency has been correlated with increased TNF-a, IL-6, and IL-10 mRNA in peripheral blood mononuclear cells. Iron deficiency is common and results in iron deficiency anemia, associated with increased susceptibility to infections, fatigue, metabolic stress, reduced cognitive functions and impaired growth. Iron deficiency is diagnosed when serum ferritin levels are below 12mg/L for children under 5 years of age, or below 15mg/L for those 5 years and older. In a Chinese study, combined iron and vitamin A supplementation reduced the incidence of diarrhea and respiratory illness in Chinese preschool children. Foods contain heme iron found in meat and non-heme iron found in vegetables and dairy products. The latter is less absorbed. Consumption of vitamin C together with iron improves its absorption. Meat, egg, grains, vegetables and some vegetables are rich in iron.Read too: Recommendations on the vegetarian diet for children and adolescents Considerations In short, several macro and micronutrients influence the immune response. Together, diet, microbiome and epigenetic factors act to modulate the immune system. Such complexity makes it challenging to investigate the role of a single nutrient. Further studies analyzing the optimal food intake (and blood/plasma levels) of these nutrients to achieve satisfactory immunoregulatory action are needed. However, some conclusions have already been reached and corroborated by the present work: babies should be breastfed as long as possible and foods rich in arginine, glutamine, bioactive peptides, DHA, prebiotics, zinc, iron, copper, selenium and vitamins (D, A, E, group B, C) must be offered when solids are introduced. Author:
References:
- VERDUCI, E. ; KÖGLMEIER, J. Immunomodulation in Children: The Role of the Diet.
Journal of Pediatric Gastroenterology and Nutrition, v. 73, no. 3, p. 293–298, 1 sept. 2021. doi:
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