Table 1.
Biomarkers of Environmental Enteric Dysfunction
| Domain | Biomarker | Method | Sample Type |
|---|---|---|---|
| Intestinal absorption | Mannitol recoverya | Mass spectrometry | Urine (2 h collection) |
| Intestinal inflammation | α-1 antitrypsin, neopterin, myeloperoxidase | ELISA | Stool |
| Enterocyte damage | I-FABP | ELISA | Plasma |
| Intestinal regeneration | REG-1B | ELISA | Stool |
| Intestinal barrier function | Lactulose recoverya | Mass spectrometry | Urine (2 h collection) |
| Microbial translocation | EndoCAb, LPSb, sCD14, sCD163 | ELISA | Plasma |
| Systemic inflammation | CRP, AGP | ELISA | Plasma |
| Growth hormone activity | IGF-1 | ELISA | Plasma |
In a subgroup of infants recruited to SHINE (250 human immunodeficiency virus [HIV]–unexposed infants per trial arm, and all HIV-exposed infants), urine, stool, blood, and saliva samples are collected at 3, 6, 12, and 18 months of age. At 1 month of age, paired maternal and infant stool and blood are collected.
Abbreviations: AGP, α-1 acid glycoprotein; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; EndoCAb, endotoxin core antibody; I-FABP, intestinal fatty acid binding protein; LPS, lipopolysaccharide; REG-1B, regenerating gene 1B; sCD14, soluble CD14; sCD163, soluble CD163; SHINE, Sanitation Hygiene Infant Nutrition Efficacy.
a Lactulose-mannitol (LM) testing is conducted at 3, 6, 12, and 18 months. Prior to testing, a pre-LM urine sample is collected to measure baseline mannitol. Infants are fasted for at least 30 minutes before ingesting 2 mL/kg of a solution containing mannitol (50 mg/mL) and lactulose (250 mg/mL). Total urine is collected in an adhesive bag for 2 hours, during which time the mother is encouraged to feed her infant regularly to permit collection of an adequate volume of urine. Collected urine is preserved using chlorhexidine to prevent overgrowth of bacteria, measured, and taken back to the laboratory for storage at −80°C for subsequent measurement of lactulose and mannitol concentrations by mass spectrometry.
b LPS will be measured in mothers only, because endotoxin-free conditions of blood collection cannot be guaranteed in infants.