Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults

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.