Abstract
BackgroundStunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first 2 years of a child’s life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function.ResultsHere we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old (n = 14) and 1-year-old children (n = 22) living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. Among processes altered in 1-year-old children, we identified one-carbon metabolism, the significance of which is supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3). Together, these results suggest altered one-carbon metabolism in this population of stunted children.ConclusionsThe epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting.Trial registration ClinicalTrials.gov NCT01375647. Registered 17 June 2011, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01375647.
Highlights
Stunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition
Profiling the Histone H3 acetylation on lysine 27 (H3K27ac) landscape in stunted and healthy infants We obtained samples of peripheral blood mononuclear cells (PBMC) from 18-week-old (n = 14) and 1-year-old (n = 22) Bangladeshi infants enrolled in the PROVIDE (“performance of rotavirus and oral polio vaccines in developing countries”, total of 700 enrolled children) study [19] and performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) to profile histone H3 acetylation on lysine 27 (H3K27ac) (Fig. 2a)
The results obtained using ∆height-for-age z-score (HAZ) are more informative about factors associated with the development of stunting because the HAZ score often changes dynamically during early infancy, and children born with low HAZ scores are not certain to becoming stunted, and vice versa (Fig. 2a)
Summary
Stunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first 2 years of a child’s life and is associated with developmental deficiencies and life-long health problems. Stunting is a global health problem in which a child does not reach their linear growth potential due to chronic or recurrent undernutrition. Stunting emerges within the first ~ 1000 days after conception, a crucial time in child development, and if left untreated it can lead to Kupkova et al Clin Epigenet (2021) 13:182 irreversible life-long health problems such as cognitive impairment, a dysfunctional immune system, vaccine failure, and significantly increased risk of mortality below the age of 5 years (Fig. 1) [1,2,3,4,5,6,7]. New nutritional interventions are needed, those provided to children living in urban slum areas of low- and middle-income countries [7, 15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
