Children's Immune Health

Children's Immune Health: A Nutritional and Natural-Health Reference

1. Definition and Overview

Children's immune health refers to the functional integrity and developmental adequacy of the immune system during childhood — a period spanning from birth through adolescence during which the body's defenses undergo continual maturation. The pediatric immune system is a dynamic and evolving network crucial for protecting children from infections and diseases; unlike adults, children's immune responses are characterized by a unique interplay between innate and adaptive immunity, shaped by genetic and environmental factors. Because this system is still forming, how it is supported — through nutrition, the early-life microbiome, lifestyle, and targeted natural interventions — has implications not only for short-term infection susceptibility but for long-term immune programming.

Early-life nutrition is a key determinant of infant gut microbiota development, immune maturation, and long-term health outcomes. The study of children's immune health in a nutritional and natural-health context therefore encompasses the micronutrients, macronutrients, botanical agents, dietary patterns, and lifestyle factors that the peer-reviewed literature has examined in relation to immune development, immune reactivity, and susceptibility to infection.

2. How the Pediatric Immune System Presents: Key Developmental Features

2.1 Innate vs. Adaptive Immunity in Early Life

Infants rely more on innate immunity — the immediate but non-specific immune response — due to the underdeveloped adaptive immune system. Infants are capable of mounting adaptive immune responses, but their ability to develop long-lasting immunity is limited; understanding the particularities of the neonatal adaptive immune system is therefore critical to guide the design of immune-based interventions in early life.

Although the CD4- and CD8-positive T cells are established around the 15th week of pregnancy, and mature T cells are already present in the newborn, they differ from adult T cells by being more tolerogenic and hyporesponsive to antigens. In the newborn, and through the first few months of life, around 40% of the circulating B cells are the B1 cells that only produce low-affinity IgM, and later in life they become replaced by the conventional B2 cells.

2.2 Passive Maternal Immunity and Its Waning

Newborns receive antibodies from their mothers, providing initial protection; this passive immunity wanes over time as the child's own immune system takes over. Because newborns and young children have an underdeveloped and immature immune system, they have to, at least partially, rely on the immune factors supplied by the mother.

2.3 Clinical Presentation of Reduced Immune Competence in Children

Children's immune systems are still developing, making them more susceptible to infections than adults. In the literature, impaired immune health in children presents broadly as increased frequency and severity of respiratory tract infections, gastrointestinal infections, and skin conditions. Malnutrition, for example, is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement; lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced.

2.4 The Immunological Memory Window

The child's immune system retains the memory of past infections and vaccinations, providing quicker and more effective responses to familiar pathogens. During early development, the immune system undergoes significant maturation, adapting to various pathogens while establishing immunological memory. This process occurs gradually across the first years of life, with the gut microbiome playing a central facilitating role.

3. Body Systems Involved

Children's immune health is not confined to a single organ system. The principal systems involved include:

• Lymphatic system: The thymus, lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT) are primary sites of immune cell development and activity. Thymic atrophy is an established consequence of malnutrition in children.
• Gastrointestinal system and gut microbiome: The development of the infant's microbiome in the first years of life is critical for immune system maturation, with evidence suggesting that early microbial exposures are key to training immune cells to distinguish between harmful and non-harmful antigens.
• Mucosal barriers: The respiratory and gastrointestinal mucosae represent the principal interface between pathogens and the child's immune system. Ascorbic acid supports the epithelial barrier against the entry of pathogens and the cellular functions of the innate and adaptive immune systems.
• Endocrine and metabolic systems: Nutritional status, hormone levels (including vitamin D as a secosteroid hormone), and metabolic health all modulate immune output. An optimal nutrient intake is shown to modulate immune maturation and response to inflammation, likely mediated by gut microbiota composition and function and through epigenetic mechanisms.

4. Contributing and Associated Factors

4.1 Malnutrition and Undernutrition

Malnourished children have increased risk of dying, with most deaths caused by infectious diseases; one mechanism behind this may be impaired immune function, though this immune deficiency of malnutrition had not previously been systematically reviewed. A landmark systematic review published in PLOS ONE (University of Copenhagen / Copenhagen University Hospital, 2014) reviewed 3,402 articles, of which 245 met inclusion criteria. Malnutrition was found to be associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement; lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced.

4.2 Gut Microbiome Composition

The development of the microbiota ecology parallels that of the gut mucosal immune system; accumulating evidence shows that perturbations in the gut microbiota in early life, while the immune system is still developing, can have long-lasting effects on local and systemic immune health.

The TEDDY study, a large prospective cohort, identified discrete phases of infant microbiome development: a development phase (3–14 months) characterized by rapid changes in microbiome composition heavily influenced by mode of birth and breastfeeding; a transitional phase (15–20 months) during which dietary changes such as the introduction of solid foods play a crucial role; and a stable phase (31–46 months) where the microbiome reaches a more stable and mature state resembling that of an adult's microbiome.

Childhood is a critical period for immune system development, which is greatly influenced by the gut microbiome; a number of factors affect the gut microbiome composition and diversity, including breastfeeding, formula feeding, and solid foods introduction. There is increasing evidence that disruptions in the early microbiome can lead to allergic conditions and food intolerances.

4.3 Mode of Feeding in Infancy

Breastfeeding is recognized as one of the most influential drivers of gut microbiome composition during infancy; differences in gut microbial communities between breastfed and formula-fed infants have been consistently observed and are hypothesized to partially mediate the relationships between breastfeeding and decreased risk for numerous communicable and non-communicable diseases in early life.

Breastfeeding and consumption of fiber-rich and fermented foods support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. Efforts to bridge the gap between breast milk and formula have led to the development of enriched formulas containing human milk oligosaccharides (HMOs), probiotics, prebiotics, and postbiotics; several studies have demonstrated that the gut microbiota composition of infants consuming modern formulas enriched with prebiotics more closely resembled that of breastfed infants, with increased relative abundances of Bifidobacterium.

4.4 Micronutrient Deficiency

Iron deficiency is common and results in iron deficiency anemia associated with a decrease in immune response to infections, fatigue and response to metabolic stress, reduced cognitive functions and impaired growth; iron deficiency is diagnosed when serum ferritin levels are below 12 µg/L for children less than 5 years, or below 15 µg/L for those 5 years and over.

Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc.

4.5 Physical Activity and Sedentary Behavior

Exercise has beneficial effects on the symptoms of metabolic syndrome and low-grade systemic inflammation in obese children; an Italian study demonstrated significant reductions in neutrophils, C-reactive protein, IL-6, IL-8, and other inflammatory markers in physically active obese children compared to sedentary ones.

4.6 Sleep

Sleep is essential to support the functions and health of the body, including immune system activity. Research has linked insufficient sleep duration in children to altered cytokine profiles and a greater risk of obesity and metabolic dysregulation, both of which indirectly affect immune competence.

5. Nutrients Studied in Relation to Children's Immune Health

5.1 Vitamin D

Mechanistic background: Higher vitamin D exposure in vitro induces a more tolerogenic immune response by upregulating regulatory T cell gene expression and affecting T cell subtypes and cytokine production. Vitamin D and zinc homeostasis are biochemically linked: zinc homeostasis and vitamin D functioning are linked; zinc intensifies the activity of specific vitamin D3-dependent promoters, while vitamin D augments the expression of zinc transporters such as ZnT10, aiding in maintaining zinc homeostasis.

Scientific evidence (human/clinical studies): A cross-sectional study of healthy children aged 1.8–5.9 years (n = 457) and a 12-week randomized trial using vitamin D-fortified foods in children aged 1.8–8.7 years (n = 77) in Montreal, Canada examined relationships between vitamin D status and immune function. The few previous trials that investigated whether vitamin D supplementation or food fortification affect immune function focused on incidence or severity of infection; one trial showed reduced acute upper respiratory tract infections (URTI), whereas a recent meta-analysis of supplementation trials in children under 5 years concluded that vitamin D intervention had no effect on incidence of illness. Evidence is therefore mixed, and these studies leave an important knowledge gap in children as to other potential vitamin D-related immune outcomes, including inflammatory cytokines or changes in leukocyte concentrations in blood.

In a pediatric COVID-19 context, supplementation of vitamin D was reported to decrease disease progression in pediatric patients; these studies suggest the use of vitamin D supplementation at doses of 1,000 IU/day for children under 1 year, or 2,000 IU/day for children aged 1–17 years, without observed serious side effects. This represents preliminary evidence from a specific clinical context and should not be generalized.

Evidence strength: Mixed to preliminary; evidence for a meaningful reduction in infection incidence in generally healthy, vitamin D-sufficient children is not well established. Benefit is more plausible in deficient populations.

5.2 Vitamin C (Ascorbic Acid)

Mechanistic background: Vitamin C is important for good immune function when it is part of a wholesome healthy diet; it acts as an antioxidant that protects cells from damage, and has antimicrobial properties and helps the body make antibodies that resist harmful germs. Ascorbic acid is a water-soluble micronutrient with antioxidant properties that plays a crucial role in the immune system, supporting the epithelial barrier against the entry of pathogens and the cellular functions of both the innate and adaptive immune systems.

Deficiency in children: Deficiency of vitamin C may start with mild symptoms such as lassitude or fatigue; deficiency in infants may result in bone abnormalities, such as impaired bone growth and disturbed skeletal development.

Scientific evidence: Historically, the importance of micronutrients in the immune system was based on vitamin C deficiency and the occurrence of scurvy; in the first recorded controlled clinical trial, published in 1753, James Lind demonstrated that those who consumed citrus fruit made the most remarkable recovery from scurvy. In modern pediatric studies, vitamin C has served as an active comparator (e.g., in echinacea trials) rather than as the primary intervention, limiting direct evidence about supplementation effects in already-replete children.

Evidence strength: The role of vitamin C in preventing deficiency-related immune dysfunction is well-established. Evidence that supplementation beyond dietary adequacy meaningfully reduces infection in healthy children is weak.

5.3 Zinc

Mechanistic background: Zinc is essential for the integrity of the immune system, with an important role in the maintenance, development, and activation of cells during innate and adaptive immune responses; it also plays a role in the integrity of epithelial barriers, which are essential for organism defense and prevention of pathogen entry.

Scientific evidence — diarrhea (strong evidence base): A 2024 systematic review and meta-analysis commissioned by the WHO reviewed 38 RCTs on zinc supplementation in children under 10 years with acute or persistent diarrhea. In children with acute diarrhea, zinc supplementation resulted in a greater proportion of children who recovered at last follow-up (RR = 1.07; 95% CI = 1.03–1.1; moderate certainty of evidence) and a reduction in the duration of diarrhea (MD = −13.27 hours; 95% CI = −17.66 to −8.89; moderate certainty of evidence). Based on such results, the WHO and UNICEF recommend oral zinc supplementation as a universal treatment for all children with acute diarrhea. However, according to the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN), there is not enough evidence to support its routine use in children with acute diarrhea living in Europe, where zinc deficiency is rare.

Scientific evidence — respiratory infections (mixed/negative evidence): Current evidence from the WHO suggests that zinc supplementation is not effective in the prevention or treatment of pneumonia. To date, studies evaluating zinc supplementation for the treatment of pneumonia have focused specifically on recovery from respiratory symptoms, with a relative lack of data regarding other important outcomes such as antibiotic treatment failure, need for hospitalization, escalation to intensive care, and lower respiratory tract infection-related deaths.

Evidence strength: Moderate certainty for benefit in acute diarrhea management, particularly in low- and middle-income country contexts. Evidence for prevention or treatment of respiratory infections is not currently supportive.

5.4 Iron

Iron deficiency is common and results in iron deficiency anemia associated with a decrease in immune response to infections, fatigue and response to metabolic stress, reduced cognitive functions and impaired growth. Combined supplementation of iron and vitamin A reduced the incidence of diarrhea- and respiratory-related illnesses in Chinese preschool children. Iron status assessment in children with active infections is complicated by the fact that serum ferritin, as a biomarker to evaluate iron status, can only be used in non-inflamed patients.

Evidence strength: Well-established that iron deficiency impairs immune function. Evidence that supplementation in iron-replete children confers further immune benefit is absent.

5.5 Omega-3 Fatty Acids

Omega-3 fatty acids, with anti-inflammatory properties, help regulate the immune response, and their deficiency may lead to imbalanced reactions and chronic inflammation. Dietary omega-3 long-chain fatty acids, prebiotics, and micronutrients are beneficial to the immune system.

A randomized, double-blind, placebo-controlled trial in iron-deficient South African schoolchildren found that n-3 long-chain PUFAs reduced respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren (published in the American Journal of Clinical Nutrition, 2015).

Evidence strength: Preliminary. Omega-3 fatty acids have plausible mechanisms in immune regulation, and some clinical data support reduced inflammatory markers; however, dedicated, large RCTs in generally healthy children are lacking.

5.6 Vitamin A

Vitamin A is a well-established micronutrient for immune function in children, particularly recognized in the context of deficiency in low-income countries. Foods rich in vitamin A, alongside zinc, iron, copper, selenium, and vitamins D, E, group B, and C, should be offered to stimulate immune function in children. Vitamin A deficiency is recognized by WHO and UNICEF as a significant contributor to child mortality from infectious diseases in deficient populations, though this reference source was not directly retrieved in full in this search.

Evidence strength: Strong evidence for correction of deficiency; benefit in replete populations is not supported.

5.7 Protein and Amino Acids

Proteins are essential for the proper functioning of immune cells, including T and B cells, and influence the production of cytokines that regulate immune responses; the complement system, involved in inflammation and pathogen destruction, also requires sufficient protein; moreover, proteins contribute to wound healing, and their deficiency can impair tissue repair. Protein and amino acid deficiencies can compromise innate and adaptive immune functions, particularly following injury or during illness.

6. Herbs and Natural Ingredients: Traditional Use and Scientific Evidence

6.1 Echinacea (Echinacea purpurea, E. angustifolia, E. pallida)

Traditional use: Echinacea species were used by numerous Indigenous peoples of North America — including the Plains tribes — as a remedy for infections, wounds, snake bites, and various inflammatory conditions. It was adopted into Western herbal medicine in the late 19th century primarily for "blood purification" and immune support during colds and fevers, most commonly prepared as a tincture or decoction of the root or aerial parts.

Scientific evidence — adults and children: One recent study found that echinacea might reduce the chance of respiratory tract infection and associated complications in children, but overall, there isn't enough evidence to support a clear connection, according to the NIH National Center for Complementary and Integrative Health (NCCIH).

A 2021 randomized, blinded, controlled clinical trial (Ogal et al., published in European Journal of Medical Research) examined Echinacea purpurea extract (Echinaforce® Junior tablets, 400 mg) versus 50 mg vitamin C as active control, given three times daily for two periods of two months to children aged 4–12 years. Overall, 429 cold days occurred in 103 children with echinacea compared to 602 days in 98 children with vitamin C (p < 0.001); echinacea prevented 32.5% of RTI episodes, resulting in an odds ratio of OR = 0.52 (95% CI 0.30–0.91, p = 0.021).

A meta-analysis of 30 clinical studies covering 5,652 participants found that echinacea reduced viral respiratory infections by 32%, and the progression to secondary complications and the subsequent need for antibiotics by up to 56% and 71%, respectively (p < 0.05). The RTI preventive benefits were primarily attributed to echinacea's antiviral effects, with multiple phytochemical compounds shown to interfere with pathogen-ligand/host-receptor interactions; anti-inflammatory and immune-modulatory actions were revealed under in vitro and ex vivo conditions.

Recent NCCIH-sponsored research suggests that the activity of echinacea extracts is influenced by soil conditions that affect the plant's bacterial community, highlighting the importance of standardization and sourcing in interpreting study results.

Evidence strength: Preliminary to moderate. While some RCTs and meta-analyses show benefit in reducing RTI frequency and complications in children, heterogeneity in formulations, preparations, and populations limits firm conclusions. The NCCIH characterizes the evidence as insufficient for a clear connection.

6.2 Elderberry (Sambucus nigra)

Traditional use: European folk medicine has a centuries-long tradition of using elderberry flowers and berries as remedies for colds, fever, and respiratory complaints. Preparations included syrups, wines, teas, and poultices. The berries were also used in Nordic and Central European traditional medicine to support the body during febrile illness.

Scientific evidence: Elderberry has traditionally been used to prevent and treat respiratory problems. A systematic review published in BMC Complementary Medicine and Therapies (PMC, 2021) examined elderberry for the prevention and treatment of viral respiratory illnesses. There is low-certainty evidence that fewer people receiving an echinacea/elderberry product may recover after one day compared to people receiving oseltamivir (RR 0.36, 95% CI 0.10 to 1.30), low-certainty evidence of little to no differences in recovery rates at three days (RR 1.03, 95% CI 0.85–1.25), and moderate-certainty evidence of no difference at five days (RR 1.06, 95% CI 0.99–1.14).

A meta-analysis cited by NCCIH (Complementary Therapies in Medicine, 2019) found that black elderberry (Sambucus nigra) supplementation effectively treated upper respiratory symptoms across randomized, controlled clinical trials. Most trials in the literature have been conducted in adults, and during the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of "cytokine storm." Pediatric-specific clinical evidence remains sparse.

Evidence strength: Low certainty overall; predominantly adult data; pediatric-specific evidence is lacking. Traditional use is well-documented, but clinical evidence base is limited and of mixed quality.

6.3 Probiotics and Gut Microbiome Modulators

Traditional use: Fermented foods — including yogurt, kefir, sauerkraut, and miso — have been consumed across diverse cultures for millennia, and the health-conferring qualities of these foods were recognized long before the microbial sciences. Their use in supporting children's digestive and overall health is embedded in traditional diets worldwide.

Scientific evidence: Probiotics labeled "infant-type bifidobacteria" (ITB), such as B. longum subsp. infantis strains, have gained significant attention in recent years for their potential to positively influence the gut microbiome, early immune system development, and consequently future health. However, significant knowledge gaps remain regarding the actual clinical impact, the optimal strains, dosing regimens, and treatment duration.

With respect to inflammation, a larger meta-analysis of 167 clinical trials involving adults and children found that pro- and synbiotics were effective in reducing CRP and TNF-α in both healthy and diseased subjects, although a disease-dependent reduction of other specific pro-inflammatory markers was also observed. However, the evidence from clinical trials that specific probiotics improve health is compromised by the large number of different probiotics that are evaluated, with few studies evaluating the same strains; there is also considerable diversity in participants recruited and inflammatory markers measured.

With respect to atopic dermatitis (eczema) — an immune-mediated condition common in children — a 2024 systematic review and meta-analysis of RCTs found that some studies suggest that probiotics may reduce SCORAD (severity) scores in children with atopic dermatitis, while other studies have found no significant difference between experimental and placebo groups. Studies have associated the increasing prevalence of pediatric allergic disorders with gradual alteration in the gastrointestinal microbiota of infants; previous reviews have demonstrated a preventive effect of some probiotics on the development of eczema; these findings align with research suggesting that changes in the infant gut microbiome modulate the immune system, potentially influencing not only allergic and atopic diseases but also infections, inflammatory conditions, and autoimmune disorders in general.

For diarrhea, Cochrane reviews (Collinson et al., 2020; Guo et al., 2019) have examined probiotics for treating acute infectious diarrhea and for the prevention of antibiotic-associated diarrhea in children. A 2025 meta-analysis noted probiotics may reduce the duration of diarrhea in children with severe acute malnutrition. Mechanistic studies suggest that probiotics may improve nutritional recovery through several pathways: modulating the composition of gut microbiota, enhancing mucosal barrier integrity, promoting nutrient uptake, and regulating immune responses via short-chain fatty acids (SCFAs) and other metabolites.

Evidence strength: Strain-specific and condition-specific. Evidence is strongest for reduction of diarrhea duration and antibiotic-associated diarrhea. Evidence for prevention of atopic conditions is preliminary and inconsistent. Overall, the field is complicated by substantial heterogeneity in strains, dosages, and outcome measures across studies.

6.4 Human Milk Oligosaccharides (HMOs) and Prebiotics

Traditional context: Human milk has always contained HMOs, which constitute the third most abundant solid component of breast milk; their immune-modulating role through the gut microbiome is only now being fully characterized scientifically.

Scientific evidence: Breastmilk contains factors that can affect key players in allergy development such as gut barrier function, the gut microbiota, and oral tolerance induction. Several studies have demonstrated that the gut microbiota composition of infants consuming modern formulas enriched with prebiotics more closely resembled that of breastfed infants, with increased relative abundances of Bifidobacterium and decreased relative abundances of Enterobacteriaceae and Peptostreptococcaceae.

Evidence strength: Growing and generally positive body of evidence for HMOs and prebiotic supplementation in formula; the research base is expanding rapidly but optimal prebiotic formulations for immune outcomes in children are not fully defined.

7. Dietary Patterns and Lifestyle Factors

7.1 Overall Diet Quality

Foods rich in arginine, glutamine, bioactive peptides, docosahexaenoic acid, prebiotics, zinc, iron, copper, selenium, and vitamins (D, A, E, group B, C) should be offered to stimulate immune function in children; nutrition counselling should start early in life, emphasizing the importance of foods with immune-modulating properties, promoting healthy eating.

Breastfeeding and consumption of fiber-rich and fermented foods support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. Dietary modulation of immune function in early life is an important and relevant approach, which can help to support immune health in the first 1,000 days of life.

7.2 Breastfeeding as a Dietary Foundation

Exclusive breastfeeding is recommended for the first six months of life, but many infants receive pumped milk, formula, donor human milk, or other nutritional sources during this critical period; substantive evidence shows early nutrition influences development of the microbiome and immune system, affecting lifelong health.

A large, multi-center study confirmed that breastfeeding status was the most significant factor associated with microbiome structure in early life.

7.3 Introduction of Solid Foods

During the transitional microbiome phase (15–20 months), the microbiome begins to show signs of settling but is still undergoing significant shifts in its composition; dietary changes, such as the introduction of solid foods, play a crucial role in this phase. Several studies have demonstrated that breastfeeding promotes a favorable microbiome; in contrast, formula feeding and the early incorporation of certain solid foods may adversely affect microbiome development.

7.4 Physical Activity

The primary approach to preventing childhood obesity is lifestyle modification including physical activity; exercising has beneficial effects on the symptoms of metabolic syndrome and low-grade systemic inflammation in obese children. Physical activity's ability to reduce inflammatory markers in children — including C-reactive protein, IL-6, and IL-8 — has been demonstrated in Italian pediatric studies, representing a plausible indirect pathway for immune support.

7.5 Sleep

Sleep is essential to support the functions and health of the body, including immune system activity. The relationship between sleep and immune function in children is an active area of research; longitudinal cohort data (e.g., from the EDEN birth cohort) have associated sleep duration trajectories with specific serum cytokine levels at age 5, suggesting that adequate sleep is one modifiable lifestyle determinant of immune competence in early childhood.

8. Evidence Gaps and Research Limitations

Across the literature on children's immune health in a nutritional context, several consistent limitations emerge:

• More information regarding the optimal dietary intake (and blood/plasma levels) to achieve an immunoregulatory action of specific nutrients in children is desirable; well-designed intervention studies investigating the effects of whole dietary patterns on the immune system are needed.
• The evidence from clinical trials that specific probiotics improve health is compromised by the large number of different probiotics evaluated, with few studies evaluating the same strains; there is also substantial diversity regarding the participants recruited and inflammatory markers measured.
• The majority of studies on zinc supplementation and respiratory infections were conducted in low- and middle-income countries, making the conclusions most applicable to those settings.
• Better design of human clinical studies addressing dosage and combinations of micronutrients in different populations are required to substantiate the benefits of micronutrient supplementation.
• Significant knowledge gaps remain regarding the actual clinical impact, optimal strains, dosing regimens, and treatment duration for probiotic interventions in infants and children.

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