Quantifying lactulose and mannitol using LC-MS/MS in a clinical study of children with environmental enteric disease
L M V C Magalhães1, F A P Rodrigues1,2, J Q Filho1
1Centro de Biomedicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Insights
Environmental enteric disease (EED) in children damages the intestinal barrier. A validated LC-MS/MS method accurately measures this damage using the lactulose:mannitol ratio (LM test) in community samples.
Area of Science:
- Gastroenterology
- Analytical Chemistry
- Pediatrics
Background:
- Intestinal epithelium barrier dysfunction (DIEB) is common in early childhood, leading to severe complications, particularly in malnourished children with environmental enteric disease (EED).
- Accurate diagnosis and intervention are challenging due to limited clinical tools, necessitating advanced analytical techniques.
- The lactulose:mannitol ratio (LM test) is a key biomarker for DIEB.
Purpose of the Study:
- To validate a high-performance liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) for measuring DIEB via the LM test.
- To assess LM test in children from different socioeconomic backgrounds in Fortaleza, Ceará.
- To confirm the utility of LC-MS/MS for detecting EED biomarkers in community settings.
Main Methods:
- Method validation included laboratory parameters: limit of detection (LD), limit of quantification (LQ), specificity, linearity, accuracy, and precision.
- Community samples were collected from children in Fortaleza, Ceará, categorized by Human Development Index (HDI).
- The EED group comprised children from low HDI areas (0.000–≤0.499), while the control group was from high HDI areas (>0.8).
Main Results:
- The LC-MS/MS method validation demonstrated acceptable standards for detection and recovery.
- Children in the EED group exhibited significantly lower mannitol excretion compared to controls (P<0.0001).
- The LM ratio was significantly higher in the EED group than in the control group (P<0.0001), indicating increased intestinal permeability.
Conclusions:
- A robust LC-MS/MS analytical approach was successfully validated for measuring the LM test in community samples.
- This sensitive method confirmed significant intestinal epithelial barrier damage in populations residing in low socioeconomic conditions.
- The findings highlight the utility of advanced analytical techniques for diagnosing EED and its impact on intestinal health in vulnerable populations.
Abstract:
Dysfunction of the intestinal epithelium barrier (DIEB) is frequent and can lead to serious complications in early childhood when diagnosis and clinical intervention are limited, especially in children with environmental enteric disease and malnutrition. The use of refined analytical techniques is increasingly necessary in this context. This study aimed to validate the high-performance liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) to measure DIEB by lactulose:mannitol ratio detection (LM test) in samples of children with different social profiles from Fortaleza, Ceará. The first experimental set was conducted to validate the method through laboratory parameters, such as limit of detection (LD), limit of quantification (LQ), specificity/selectivity, linearity, accuracy, and precision. All validation parameters achieved detection and recovery standards within an acceptable coefficient of variation. Community samples (human development index (HDI) from 0.000 to ≤0.499) were obtained from children from the cohort study Malnutrition-Enteric Diseases, Fortaleza-CE (environmental enteric disease; EED group). The control group samples came from a school located in a region with a high HDI (>0.8). Mannitol excretion was lower in the EED group than in the control group (P<0.0001). On the other hand, LM was higher in this group compared to the control group (P<0.0001). For the first time, a robust analytical approach was used to detect biomarkers of environmental enteropathy (LM) in community samples, confirming with high-sensitivity the damage to the intestinal epithelial barrier function in populations living in low socio-economic conditions.
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