TY - JOUR
T1 - Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study
AU - EEDBI Consortium
AU - Iqbal, Najeeha T.
AU - Lawrence, Sarah
AU - Ahmed, Tahmeed
AU - Chandwe, Kanta
AU - Fahim, Shah M.
AU - Houpt, Eric R.
AU - Kabir, Furqan
AU - Kelly, Paul
AU - Liu, Jie
AU - Mahfuz, Mustafa
AU - Mweetwa, Monica
AU - VanBuskirk, Kelley
AU - Tarr, Phillip I.
AU - Denno, Donna M.
AU - Ahmed, Kumail
AU - Ahmed, Sheraz
AU - Alam, Md Ashraful
AU - Ali, S. Asad
AU - Amadi, Beatrice
AU - Das, Subhasish
AU - Gazi, Md Amran
AU - Haque, Rashidul
AU - Hasan, Md Mehedi
AU - Hossain, Md Shabab
AU - Hotwani, Aneeta
AU - Hussain, Shahneel
AU - Iqbal, Junaid
AU - Jakhro, Sadaf
AU - Liu, Ta Chiang
AU - Mazumder, Ramendra Nath
AU - Moskaluk, Christopher A.
AU - Qureshi, Abdul Khalique
AU - Raghavan, Shyam S.
AU - Rahman, Masudur
AU - Rahman, Najeeb
AU - Sadiq, Kamran
AU - Sarker, Shafiqul Alam
AU - Sullivan, Peter B.
AU - Tearney, Guillermo J.
AU - Umrani, Fayaz
AU - Yilmaz, Omer H.
AU - Zyambo, Kanekwa
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9
Y1 - 2024/9
N2 - Background: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease. Objectives: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology. Methods: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data. Results: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [β 0.2 (95% CI: 0.1, 0.3); P = 0.002 and β 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [β 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [β 4.2 (95% CI: 0.8, 7.7); P = 0.017 and β 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters. Conclusions: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.
AB - Background: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease. Objectives: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology. Methods: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data. Results: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [β 0.2 (95% CI: 0.1, 0.3); P = 0.002 and β 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [β 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [β 4.2 (95% CI: 0.8, 7.7); P = 0.017 and β 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters. Conclusions: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.
KW - LMIC
KW - TAC
KW - enteropathogens
KW - environmental enteric dysfunction
KW - qPCR
KW - virulence loci
UR - http://www.scopus.com/inward/record.url?scp=85204011596&partnerID=8YFLogxK
U2 - 10.1016/j.ajcnut.2024.02.026
DO - 10.1016/j.ajcnut.2024.02.026
M3 - Article
AN - SCOPUS:85204011596
SN - 0002-9165
VL - 120
SP - S84-S93
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
ER -