Abstract
In many countries, there is a tendency towards an increase
in the number of patients, particularly children and adolescents,
with metabolic disorders, such as insulin resistance, metabolic
syndrome, obesity, impaired glucose tolerance, type 2 diabetes
(T2D), which lead to serious consequences for human health. A
significant number of studies indicate that the intestinal microbiota
significantly affects the development of metabolic disorders (MD),
and a promising biological non-invasive biomarker of increased intestinal
permeability is considered to be human zonulin – the only
known physiological modulator which increases intestinal permeability
by interacting with a mammalian cell receptor and subsequent
activation of intracellular signaling, leading to the destruction
of intercellular tight junctions. This review focuses on studies
indicating that zonulin is a key regulator of intestinal permeability
associated with the development of chronic metabolic diseases in
childhood and adolescence. Zonulin may play a role not only as a
marker of intestinal permeability disorders, but also as a possible
indicator of early MD in children and adolescents with overweight/
obesity, helping to identify children and adolescents at risk of MD
even at an early stage and implement targeted and timely preventive
measures. The aim. To analyze the literature data to determine
the role of zonulin as an early marker of MD in children and adolescents.
Material and methods. A comprehensive literature review
was conducted using relevant keywords in PubMed, Scopus, and
Google Scholar search engines. According to the keywords «zonu-lin», «metabolic disorders», «insulin resistance»; «obesity», «type 2
diabetes», «intestinal permeability», «children and adolescents» 61
literature sources were selected for in-depth analysis. Conclusions.
Literature data indicate that the intestinal microbiota significantly
affects the development of MD, and an important factor involved
in the regulation of intestinal barrier permeability is zonulin – an
endogenous protein that modulates intercellular tight junctions
in the epithelium of the small intestine. Increased zonulin levels
can serve as an early diagnostic marker of metabolic disorders in
childhood and adolescence. According to the results of studies, increased
zonulin levels are associated with overweight/obesity, insulin
resistance, T2D and other MD in both adults and children. Further
research is needed for a deeper understanding of the pathophysiological
role of zonulin, as well as for the development of effective
methods for the prevention and treatment of MD.
References
risk for type 2 diabetes. Curr Nutr Rep. 2020 Jun;9(2):83-93. doi:
10.1007/s13668-020-00307-3.
2. Agus A, Clément K, Sokol H. Gut microbiota-derived metabolites
as central regulators in metabolic disorders. Gut. 2021
Jun;70(6):1174-82. doi: 10.1136/gutjnl-2020-323071.
3. Lebovitz HE. Insulin resistance: definition and consequences.
Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S135-48. doi:
10.1055/s-2001-18576. PMID: 11460565.
4. Bjerregaard LG, Jensen BW, Ängquist L, Osler M, Sørensen TIA,
Baker JL. Change in overweight from childhood to early adulthood
and risk of type 2 diabetes. N Engl J Med. 2018 Apr 5;378(14):1302-
12. doi: 10.1056/NEJMoa1713231.
5. World Health Organization. Regional Office for Europe WHO European Regional Obesity Report 2022. Copenhagen:
WHO Regional Office for Europe; 2022. [cited 2025 May 08].
Available from: https://apps.who.int/iris/bitstream/hand
le/10665/353747/9789289057738-eng.pdf
6. Arends NJ, Boonstra VH, Duivenvoorden HJ, Hofman PL,
Cutfield WS, Hokken-Koelega AC. Reduced insulin sensitivity
and the presence of cardiovascular risk factors in short
prepubertal children born small for gestational age (SGA). Clin
Endocrinol (Oxf). 2005 Jan;62(1):44-50. doi: 10.1111/j.1365-
2265.2004.02171.x.
7. Stąpor N, Beń-Skowronek I. Insulin resistance in childrenPediatr
Endocrinol Diabetes Metab. 2015;20(3):107-15. Polish. doi:
10.18544/PEDM-20.03.0010.
8. Caricilli AM, Saad MJ. The role of gut microbiota on insulin
resistance. Nutrients. 2013 Mar 12;5(3):829-51. doi: 10.3390/
nu5030829.
9. Diamant M, Blaak EE, de Vos WM. Do nutrient-gut-microbiota
interactions play a role in human obesity, insulin resistance and type
2 diabetes? Obes Rev. 2011 Apr;12(4):272-81. doi: 10.1111/j.1467-
789X.2010.00797.x.
10. Vangipurapu J, Fernandes Silva L, Kuulasmaa T, Smith U, Laakso M.
Microbiota-related metabolites and the risk of type 2 diabetes.
Diabetes Care. 2020 Jun;43(6):1319-25. doi: 10.2337/dc19-2533.