TY - JOUR
T1 - Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults
AU - Kelly, Paul
AU - Amadi, Beatrice
AU - Chandwe, Kanta
AU - Besa, Ellen
AU - Zyambo, Kanekwa
AU - Chama, Mubanga
AU - Tarr, Phillip I.
AU - Shaikh, Nurmohammad
AU - Ndao, I. Malick
AU - Storer, Chad
AU - Head, Richard
N1 - Funding Information:
The study was designed by BA and PK, and data collection was designed and supervised by EB, KZ, KC, NS, IMN and PK. First level transcriptomic analysis was carried out by MC and PK, and further analysis designed and carried out by PIT, CS, and RH. All authors have read and approved the final version of the manuscript. Data verification was carried out by PK, CS and RH. Processed data are available for all groups as fragments per kilobase mapped (FPKM) at https://datadryad.org/stash/share/CEApzEmW2uApkomDxSRE5EgDuBZT0dA1BZLSuXoN72A. Fastq data relating to stunted children have been deposited in GEO under accession number 162630. None.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/8
Y1 - 2021/8
N2 - Background: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. Methods: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. Findings: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. Interpretation: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study.
AB - Background: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. Methods: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. Findings: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. Interpretation: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study.
KW - Environmental Enteric Dysfunction
KW - Environmental enteropathy
KW - NADPH oxidase
KW - RNA sequencing
KW - intestinal digestion
KW - intestinal transport
KW - malnutrition
KW - xenobiotic metabolism
UR - http://www.scopus.com/inward/record.url?scp=85111250085&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2021.103509
DO - 10.1016/j.ebiom.2021.103509
M3 - Article
C2 - 34333236
AN - SCOPUS:85111250085
SN - 2352-3964
VL - 70
JO - EBioMedicine
JF - EBioMedicine
M1 - 103509
ER -