Malnutrition, Vitamin Deficiencies, the Immune System and Infections: Time to

Revisit Our Knowledge

Raz Somech, MD, PhD, Pediatric Immunology, Jeffrey Modell Foundation (JMF)
Center, Edmond and Lily Safra Childrens Hospital, Chaim Sheba Medical Center,
Tel Hashomer, 52621, affiliated to the "Sackler" Faculty of Medicine, Tel Aviv
University, Tel Aviv, Israel, Email: raz.somech@sheba.health.gov.il
Our immune system needs its nutrition in order to function efficiently in
protecting our body against infections. Infections are frequent and chronic in
malnourished patients. Recent discoveries provide new information and new
challenges regarding the link between nutrition and infections. Almost 900 million
people in the world are undernourished. Malnutrition is the primary cause of
immunodeficiency worldwide with infants, children, adolescents, and the elderly most
affected. Malnutrition in relation to the immune system can be classified into proteinenergy malnutrition and micronutrient deficiencies. Both conditions are associated
with significant impairments of cell-mediated immunity, antibody concentrations,
phagocyte function, complement system, and cytokine production (1). Several studies
report effects of nutrients and by-products of microbial metabolism on the expression
of antimicrobial peptide genes in order to highlight an emerging appreciation for the
role of dietary compounds in modulating the immune response (2).
Specific aims that will be discussed in the presentation are:
1. Contribution of deficiency in selected water-soluble and fat-soluble vitamins and
trace element micronutrients to immune dysfunction.
2. The effect of malnutrition on the thymus gland.
3. The gut microbiota involvement in severe acute malnutrition.
Micronutrient deficiencies have effects such as poor growth, impaired
intellect, and increased mortality and susceptibility to infection. Their deficiency
affects the innate T-cell-mediated immune response and adaptive antibody response.
Infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing
losses, and interfering with utilization by altering metabolic pathways. Antioxidant
vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract
potential damage caused by reactive oxygen species to cellular tissues, modulate
immune cell function and affect production of cytokines and prostaglandins.
Adequate intake of vitamins B 6 , folate, B 12 , C, E, and of selenium, zinc, copper,
and iron supports a Th1 cytokine-mediated immune response and avoids a shift to an
anti-inflammatory Th2 cell-mediated immune response. Vitamins A and D play
important roles in both cell-mediated and humoral antibody response and support a
Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both
innate immunity (mucosal epithelial regeneration) and adaptive immune response to
infection resulting in an impaired ability to counteract extracellular pathogens.
Vitamin D deficiency is correlated with a higher susceptibility to infections due to
impaired localized innate immunity and defects in antigen-specific cellular immune
response (3,4).
The gut microbiota include an enormous number of microorganisms located in
our gut. They act at the interface between the host and nutritional intake to modulate
not only immune functions but also metabolic pathways. Recent discoveries on how
the gut microbiota are also involved in severe acute malnutrition illuminate their

fundamental role in the pathogenesis of severe acute malnutrition (5). In children with
kwashiorkor, the microbiotas' metabolic capacity affects the development of the
disease (6). Moreover, antibiotic therapy together with ready-to-use therapeutic food
improved recovery and reduced mortality in children with kwashiorkor (7). These
findings suggest that an immature gut microbiome is an important contributing factor
in children with kwashiorkor.
The thymus gland is the main organ for cellular immunity including T cell
development, maturation and self- tolerance. Malnutrition due to protein energy
deficiency results in changes in the thymus. This includes severe atrophy due to
apoptosis-induced thymocyte depletion, as well as a decrease in cell proliferation. The
micro environmental compartment of the thymus is also affected in acute infections
which are common in malnourished patients (8). Profound changes in the thymus can
also be seen in deficiencies of vitamins and trace elements. These changes can be
reversed by appropriate supplementation (9). Strategies inducing thymus
replenishment should be considered in therapeutic approaches in malnutrition.
References:
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Infect Dis. 2008;46(10):1582-8.
2. Campbell Y, Fantacone ML, Gombart AF. Regulation of antimicrobial peptide
gene expression by nutrients and by-products of microbial metabolism. Eur J
Nutr. 2012;51(8):899-907.
3. Wintergerst ES, Maggini S, Hornig DH. Contribution of selected vitamins and
trace elements to immune function. Ann Nutr Metab. 2007;51(4):301-23
4. Cunningham-Rundles S, McNeeley DF, Moon A. Mechanisms of nutrient
modulation of the immune response. J Allergy Clin Immunol.
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6. Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for
kwashiorkor. Science. 2013; 339:548554.
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malnutrition. N. Engl. J. Med. 2013; 368:425435.
8. Savino W, et al. The thymus is a common target in malnutrition and infection.
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thymus: consequences on T-cell-mediated immune responses. Proc Nutr Soc.
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