TY - JOUR
T1 - Duodenal microbiota in stunted undernourished children with enteropathy
AU - Chen, Robert Y.
AU - Kung, Vanderlene L.
AU - Das, Subhasish
AU - Hossain, M. Shabab
AU - Hibberd, Matthew C.
AU - Guruge, Janaki
AU - Mahfuz, Mustafa
AU - Begum, Khodeza Nahar
AU - Rahman, M. Masudur
AU - Fahim, Shah Mohammad
AU - Gazi, M. Amran
AU - Haque, Rashidul
AU - Sarker, Shafiqul A.
AU - Mazumder, Ramendra N.
AU - Di Luccia, Blanda
AU - Ahsan, Kazi
AU - Kennedy, Elizabeth
AU - Santiago-Borges, Jesus
AU - Rodionov, Dmitry A.
AU - Leyn, Semen A.
AU - Osterman, Andrei L.
AU - Barratt, Michael J.
AU - Ahmed, Tahmeed
AU - Gordon, Jeffrey I.
N1 - Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.
PY - 2020/7/23
Y1 - 2020/7/23
N2 - BACKGROUND Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r=−0.49; P=0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED.
AB - BACKGROUND Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r=−0.49; P=0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED.
UR - http://www.scopus.com/inward/record.url?scp=85088429919&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1916004
DO - 10.1056/NEJMoa1916004
M3 - Article
C2 - 32699454
AN - SCOPUS:85088429919
SN - 0028-4793
VL - 383
SP - 321
EP - 333
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 4
ER -