Critical to the design and assessment of interventions for enteropathy and its
developmental consequences in children living in impoverished conditions are
non-invasive biomarkers that can detect intestinal damage and predict its effects
on growth and development. We therefore assessed fecal, urinary and systemic
biomarkers of enteropathy and growth predictors in 375 6-26 month-old children
with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301
of these children returned for followup anthropometry after 2-6m. Biomarkers
that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin
(if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption);
and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting
impaired defenses). In contrast, subsequent growth was predicted in those with
higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and
SAA (showing intestinal barrier disruption and inflammation). Better growth was
predicted in girls with higher plasma citrulline and in boys with higher plasma
tryptophan. Interactions were also seen with fecal MPO and neopterin in
predicting subsequent growth impairment.
Biomarkers clustered into markers of 1) functional intestinal barrier disruption and
translocation, 2) structural intestinal barrier disruption and inflammation and 3)
systemic inflammation. Principle components pathway analyses also showed
that L/M with %L, I-FABP and MPO associate with impaired growth, while also
(like MPO) associating with a systemic inflammation cluster of kynurenine, LBP,
sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with
stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low
zonulin) associated with fecal MPO and neopterin.
We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS
translocation and of intestinal and systemic inflammation can help elucidate how
we recognize, understand, and assess effective interventions for enteropathy and
its growth and developmental consequences in children in impoverished settings.