TABLE 1.
Domains of EED and its sequelae, corresponding biomarkers, and assays used in the SHINE (Sanitation Hygiene Infant Nutrition Efficacy) trial1
| Assay | ||||
|---|---|---|---|---|
| Biomarker | Rationale and previous reports | Platform and manufacturer | Limit of detection | |
| EED domain | ||||
| Altered intestinal architecture | Plasma intestinal fatty acid binding protein | Found mostly at tips of small intestinal villi. Released into circulation after epithelial damage (48) | ELISA, Hycult Biotechnology, Uden, Netherlands | 47 pg/mL |
| Plasma citrulline | Biomarker of total intestinal mass (38, 49) | Chromatography tandem MS with electrospray ionization, Waters, Wilmslow, United Kingdom | 100 ng/mL | |
| Impaired intestinal regeneration | Fecal regenerating gene 1β | Stool regenerating gene protein, which is a measure of intestinal injury and repair (36, 38) | ELISA, TECHLAB Inc, Blacksburg, VA, USA | 0.625 ng/mL |
| Intestinal permeability | Fecal α-1 antitrypsin | Indicates leakage of plasma protein into intestine (35) | ELISA, BioVendor, Brno, Czech RepublicProminence LC (Shimadzu) with mass spectrometer with electrospray ionization (Restek column SciexQTRAP5000) |
1.5 ng/mL1 ng/mL for both sugars |
| Urinary lactulose:mannitol ratio | Uptake of large sugar (lactulose) through impaired intestinal barrier and reduced mannitol absorption due to reduced surface area (20) | |||
| Microbial translocation | Plasma soluble CD14 | Marker of LPS stimulation of monocytes (50) | ELISA, R&D Systems, Minneapolis, MN, USA | 125 pg/mL |
| Intestinal inflammation | Fecal myeloperoxidase | Biomarker of gut inflammation (51, 53) | ELISA, Immundiagnostik, Bensheim, Germany | 1.6 ng/mL |
| Fecal neopterin | Biomarker of gut inflammation (53) | ELISA, GenWay Biotech, Inc., San Diego, CA, USA | 0.7 nmol/L | |
| Systemic sequelae | ||||
| Systemic inflammation | Plasma C-reactive protein | Acute-phase protein | ELISA, R&D Systems, Minneapolis, MN, USA | 0.01 ng/mL |
| Plasma kynurenine-to-tryptophan ratio | Induction of IDO enzyme in response to inflammation (52) | Ultra-high performance LC tandem MS with electrospray ionization, Waters, Wilmslow, United Kingdom | 40 ng/mL (kynurenine)200 ng/mL (Trp) | |
| Growth-hormone axis | Plasma insulin-like growth factor 1 | Required at growth plate to mediate effects of growth hormone (54, 55) | ELISA, R&D Systems, Minneapolis, MN, USA | 0.026 ng/mL |
1
EED, environmental enteric dysfunction; IDO, Indoleamine-pyrrole 2,3-dioxygenase.