Improving the detection of environmental enteric dysfunction: A lactulose, rhamnose assay of intestinal permeability in children aged under 5 years exposed to poor sanitation and hygiene

W. A. Faubion, M. Camilleri, J. A. Murray, P. Kelly, B. Amadi, M. N. Kosek, F. Enders, J. Larson, Madhusudan Grover, G. Boe, R. Dyer, R. Singh

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Abstract

Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. Methods: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. Findings: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was −0.1 (−1.8 to 2.4), −1.8 (−3.3 to −0.2) and −2.3 (−8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). Conclusions: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.

Original languageEnglish (US)
Article numbere000066
JournalBMJ Global Health
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2016

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Lactulose
Rhamnose
Sanitation
Hygiene
Zambia
Peru
Permeability
Urine
Monosaccharides
Disaccharides
Social Conditions
Mass Spectrometry
High Pressure Liquid Chromatography
Weights and Measures
Growth
Population

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health Policy

Cite this

@article{c70f52e5f30240f9971c0ea0d1e52e9b,
title = "Improving the detection of environmental enteric dysfunction: A lactulose, rhamnose assay of intestinal permeability in children aged under 5 years exposed to poor sanitation and hygiene",
abstract = "Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. Methods: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. Findings: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was −0.1 (−1.8 to 2.4), −1.8 (−3.3 to −0.2) and −2.3 (−8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). Conclusions: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.",
author = "Faubion, {W. A.} and M. Camilleri and Murray, {J. A.} and P. Kelly and B. Amadi and Kosek, {M. N.} and F. Enders and J. Larson and Madhusudan Grover and G. Boe and R. Dyer and R. Singh",
year = "2016",
month = "1",
day = "1",
doi = "10.1136/bmjgh-2016-000066",
language = "English (US)",
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journal = "BMJ Global Health",
issn = "2059-7908",
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TY - JOUR

T1 - Improving the detection of environmental enteric dysfunction

T2 - A lactulose, rhamnose assay of intestinal permeability in children aged under 5 years exposed to poor sanitation and hygiene

AU - Faubion, W. A.

AU - Camilleri, M.

AU - Murray, J. A.

AU - Kelly, P.

AU - Amadi, B.

AU - Kosek, M. N.

AU - Enders, F.

AU - Larson, J.

AU - Grover, Madhusudan

AU - Boe, G.

AU - Dyer, R.

AU - Singh, R.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. Methods: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. Findings: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was −0.1 (−1.8 to 2.4), −1.8 (−3.3 to −0.2) and −2.3 (−8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). Conclusions: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.

AB - Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. Methods: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. Findings: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was −0.1 (−1.8 to 2.4), −1.8 (−3.3 to −0.2) and −2.3 (−8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). Conclusions: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.

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