TY - JOUR
T1 - Duodenal quantitative mucosal morphometry in children with environmental enteric dysfunction
T2 - a cross-sectional multicountry analysis
AU - Ehsan, Lubaina
AU - Coomes, David
AU - Kelly, Paul
AU - Greene, Adam R.
AU - Ali, S. Asad
AU - Mulenga, Chola
AU - Denno, Donna M.
AU - VanBuskirk, Kelley
AU - Raghib, Muhammad Faraz
AU - Mahfuz, Mustafa
AU - Moore, Sean R.
AU - Hossain, Md Shabab
AU - Ahmed, Tahmeed
AU - Sullivan, Peter B.
AU - Moskaluk, Christopher A.
AU - Syed, Sana
AU - Kumail, Ahmed
AU - Sheraz, Ahmed
AU - Ashraful, Alam Md
AU - Khodeza Nahar, Begum SM
AU - Subhasish, Das
AU - Lee A, Denson
AU - Mohammad, Fahim Shah
AU - Amran, Gazi Md
AU - Mehedi, Hasan Md
AU - Aneeta, Hotwani
AU - Junaid, Iqbal
AU - Talat, Iqbal Najeeha
AU - Zehra, Jamil
AU - Furqan, Kabir
AU - Ta-Chiang, Liu
AU - Nath, Mazumder Ramendra
AU - Shyam S, Ragahavan
AU - Masudur, Rahman
AU - Najeeb, Rahman
AU - Kamran, Sadiq
AU - Alam, Sarker Shafiqul
AU - Phillip I, Tarr
AU - Guillermo J, Tearney
AU - Fayaz, Umrani
AU - Grace, Umutesi
AU - Omer H, Yilmaz
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/9
Y1 - 2024/9
N2 - Background: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. Objectives: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. Methods: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n = 69), and those with no pathologic abnormality (NPA; n = 8) or celiac disease (n = 18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared with NPA or celiac disease and identify associations between morphometry and histology or immunohistochemistry among children with EED. Results: In duodenal biopsies, median EED villus height (248 μm), crypt depth (299 μm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 μm villus height; 246 μm crypt depth; 1.6 V:C ratio) and celiac disease (208 μm villus height; 365 μm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist-determined subjective semiquantitative villus architecture. Conclusions: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides, although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. Although acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.
AB - Background: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. Objectives: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. Methods: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n = 69), and those with no pathologic abnormality (NPA; n = 8) or celiac disease (n = 18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared with NPA or celiac disease and identify associations between morphometry and histology or immunohistochemistry among children with EED. Results: In duodenal biopsies, median EED villus height (248 μm), crypt depth (299 μm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 μm villus height; 246 μm crypt depth; 1.6 V:C ratio) and celiac disease (208 μm villus height; 365 μm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist-determined subjective semiquantitative villus architecture. Conclusions: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides, although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. Although acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.
KW - crypt
KW - gastrointestinal morphology
KW - global health
KW - pediatric
KW - villi
UR - http://www.scopus.com/inward/record.url?scp=85203980577&partnerID=8YFLogxK
U2 - 10.1016/j.ajcnut.2024.04.027
DO - 10.1016/j.ajcnut.2024.04.027
M3 - Article
C2 - 38685382
AN - SCOPUS:85203980577
SN - 0002-9165
VL - 120
SP - S41-S50
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
ER -