Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 May 2:13:826268.
doi: 10.3389/fimmu.2022.826268. eCollection 2022.

Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies

Husheem Michael  1 , Joshua O Amimo  1   2 , Gireesh Rajashekara  1 , Linda J Saif  1 , Anastasia N Vlasova  1
Affiliations
Review

Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies

Husheem Michael et al. Front Immunol. .

Abstract

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children's health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus-a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.

Keywords: gnotobiotic model; human rotavirus; immunity; microbiota; protein calorie-deficient diet.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Vicious cycle of malnutrition and infection and its impacts on morbidity, mortality, and long-term disability.
Figure 2
Figure 2
Schematic depiction of pathobiological features and interactions observed in different types of malnutrition (kwashiorkor and marasmus) in children.
Figure 3
Figure 3
Comparison of clinical and immune parameters of kwashiorkor in humans, pigs, and mice.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of Childhood Malnutrition on Host Defense and Infection. Clin Microbiol Rev (2017) 30(4):919–71. doi: 10.1128/CMR.00119-16 - DOI - PMC - PubMed
    1. Scrimshaw NS. INCAP Studies of Nutrition and Infection. Food Nutr Bull (2010) 31(1):54–67. doi: 10.1177/156482651003100107 - DOI - PubMed
    1. Spoelstra MN, Mari A, Mendel M, Senga E, van Rheenen P, van Dijk TH, et al. . Kwashiorkor and Marasmus are Both Associated With Impaired Glucose Clearance Related to Pancreatic Beta-Cell Dysfunction. Metabo: Clin Experiment (2012) 61(9):1224–30. doi: 10.1016/j.metabol.2012.01.019 - DOI - PubMed
    1. Jones KD, Thitiri J, Ngari M, Berkley JA. Childhood Malnutrition: Toward an Understanding of Infections, Inflammation, and Antimicrobials. Food Nutr Bull (2014) 35(2 Suppl):S64–70. doi: 10.1177/15648265140352S110 - DOI - PMC - PubMed
    1. Prendergast A, Kelly P. Enteropathies in the Developing World: Neglected Effects on Global Health. Am J Trop Med Hyg (2012) 86(5):756–63. doi: 10.4269/ajtmh.2012.11-0743 - DOI - PMC - PubMed