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

Faubion, William A.; Camilleri, Michael; Murray, Joseph A.; Kelly, Paul; Amadi, Beatrice; Kosek, Margaret; Enders, Felicity; Larson, Jenifer; Grover, Madhusudan; Boe, G.; Dyer, Roy B.; Singh, Ravinder J.

doi:10.1136/bmjgh-2016-000066

Cited by 46 publications

(56 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…tTG IgA assay normal limits differ depending assay kit; we expressed anti-tTG concentrations as percentages of upper limits of normal for the particular kit utilized (IBL International, Germany in Pakistan, Orgentech, Germany in Zambia, Inova, California, and Quest and Labcorp in St. Louis). Additionally, biomarkers potentially reflective of EED or undernutrition processes common to at least two sites' cohorts were analyzed in this report and included urinary dual sugar (lactulose, rhamnose or lactulose, mannitol) permeability testing (Zambia and St. Louis) [41], and serum concentrations of insulin-like growth factor 1 (IGF-1) and glucagon-like peptide 2 (GLP-2) (Zambia and Pakistan). Individual data are included in S1 Dataset.…”

Section: Anthropometric Clinical and Laboratory Assessmentsmentioning

confidence: 99%

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

et al. 2020

View full text Add to dashboard Cite

BackgroundA major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. Data Availability Statement: All relevant analyses are within the manuscript and its Supporting was assessed. The histology index was further used to identify within-and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. ResultsEight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet's AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort. ConclusionsWe propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world. Author summaryThe study of EED has been limited by the lack of a rigorously tested, reproducible histology index that can provide insight to the pathogenesis of this entity. In this study we report the first duodenal histology index that was developed using an unbiased approach, with excellent inter-observer reproducibility, for the study of EED. The EED histology index readily identified histologic features that are common or unique to cohorts of distinct geographic locations. Incorporating the histology index into future clinical studies will provide useful insight into the pathogenesis and for intervention strategy development.

show abstract

Section: Anthropometric Clinical and Laboratory Assessmentsmentioning

confidence: 99%

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

et al. 2020

View full text Add to dashboard Cite

show abstract

“…EED was determined by assessing both gut permeability and inflammation. The lactulose absorption (L%) was measured via sugar absorption test, as previously described (24), and was used as a maker to assess the gut permeability of the children. Classification of EED severity was performed as previously described (25).…”

Section: Prevalence and Measurement Of Eedmentioning

confidence: 99%

“…To determine the role of Campylobacter in EED, the levels of lactulose and MPO were measured as indicators of EED (24,25). Additional details concerning the prevalence of EED and stunting among children in this study are described in Chen et al (under review).…”

Section: The Campylobacter In the Stools Was Not Associated With Diarmentioning

confidence: 99%

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

Terefe

Deblais

Ghanem

et al. 2020

Front. Public Health

View full text Add to dashboard Cite

High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360-498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41-60%) by PCR and 88% (80-93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5-12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter Terefe et al. Campylobacter and Microbiome in Stools were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple nonthermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

show abstract

“…In fact, the mass of saccharides that is absorbed during 1 hour in the healthy gut following ingestion orally is typically up to 2% of rhamnose and 0.07% of lactulose administered in children in USA 45. In healthy adults, the fractional excretion over 24 hours is 31.2%±3.4% (SEM) for 13 C-mannitol and 0.32%±0.03% for lactulose 46.…”

Section: Introductionmentioning

confidence: 99%

Leaky gut: mechanisms, measurement and clinical implications in humans

Camilleri

2019

Gut

699

448

View full text Add to dashboard Cite

The objectives of this review on ‘leaky gut’ for clinicians are to discuss the components of the intestinal barrier, the diverse measurements of intestinal permeability, their perturbation in non-inflammatory ‘stressed states’ and the impact of treatment with dietary factors. Information on ‘healthy’ or ‘leaky’ gut in the public domain requires confirmation before endorsing dietary exclusions, replacement with non-irritating foods (such as fermented foods) or use of supplements to repair the damage. The intestinal barrier includes surface mucus, epithelial layer and immune defences. Epithelial permeability results from increased paracellular transport, apoptosis or transcellular permeability. Barrier function can be tested in vivo using orally administered probe molecules or in vitro using mucosal biopsies from humans, exposing the colonic mucosa from rats or mice or cell layers to extracts of colonic mucosa or stool from human patients. Assessment of intestinal barrier requires measurements beyond the epithelial layer. ‘Stress’ disorders such as endurance exercise, non-steroidal anti-inflammatory drugs administration, pregnancy and surfactants (such as bile acids and dietary factors such as emulsifiers) increase permeability. Dietary factors can reverse intestinal leakiness and mucosal damage in the ‘stress’ disorders. Whereas inflammatory or ulcerating intestinal diseases result in leaky gut, no such disease can be cured by simply normalising intestinal barrier function. It is still unproven that restoring barrier function can ameliorate clinical manifestations in GI or systemic diseases. Clinicians should be aware of the potential of barrier dysfunction in GI diseases and of the barrier as a target for future therapy.

show abstract

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

Cited by 46 publications

References 37 publications

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

Leaky gut: mechanisms, measurement and clinical implications in humans

Contact Info

Product

Resources

About