• Robert Y Chen, Vanderlene L Kung, Subhasish Das, M Shabab Hossain, Matthew C Hibberd, Janaki Guruge, Mustafa Mahfuz, S M Khodeza Nahar Begum, M Masudur Rahman, Shah Mohammad Fahim, M Amran Gazi, Rashidul Haque, Shafiqul A Sarker, Ramendra N Mazumder, Di LucciaBlandaBFrom the Edison Family Center for Genome Sciences and Systems Biology (R.Y.C., V.L.K., M.C.H., J.G., B.D.L., K.A., E.K., J.S.-B., M.J.B., J.I.G.), the Center for Gut Microbiome and Nutrition Research (R.Y.C., V.L.K., M.C.H., J.G., K.A., M., Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Dmitry A Rodionov, Semen A Leyn, Andrei L Osterman, Michael J Barratt, Tahmeed Ahmed, and Jeffrey I Gordon.
• From the Edison Family Center for Genome Sciences and Systems Biology (R.Y.C., V.L.K., M.C.H., J.G., B.D.L., K.A., E.K., J.S.-B., M.J.B., J.I.G.), the Center for Gut Microbiome and Nutrition Research (R.Y.C., V.L.K., M.C.H., J.G., K.A., M.J.B., J.I.G.), and the Department of Pathology and Immunology (V.L.K., M.J.B., J.I.G.), Washington University School of Medicine, St. Louis; the International Center for Diarrhoeal Disease Research, Bangladesh (S.D., M.S.H., M.M., S.M.F., M.A.G., R.H., S.A.S., R.N.M., T.A.), the Department of Pathology, Dr. Sirajul Islam Medical College (S.M.K.N.B.), and Sheikh Russel National Gastroliver Institute and Hospital (M.M.R.), Dhaka, Bangladesh; the A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow (D.A.R., S.A.L.); and the Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (D.A.R., S.A.L., A.L.O.).
• N. Engl. J. Med. 2020 Jul 23; 383 (4): 321333321-333.

BackgroundEnvironmental 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).MethodsIn 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.ResultsOf 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.ConclusionsThese 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. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).Copyright © 2020 Massachusetts Medical Society.

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