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Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.
Chen, Robert Y; Kung, Vanderlene L; Das, Subhasish; Hossain, M Shabab; Hibberd, Matthew C; Guruge, Janaki; Mahfuz, Mustafa; Begum, S M Khodeza Nahar; Rahman, M Masudur; Fahim, Shah Mohammad; Gazi, M Amran; Haque, Rashidul; Sarker, Shafiqul A; Mazumder, Ramendra N; Di Luccia, Blanda; Ahsan, Kazi; Kennedy, Elizabeth; Santiago-Borges, Jesus; Rodionov, Dmitry A; Leyn, Semen A; Osterman, Andrei L; Barratt, Michael J; Ahmed, Tahmeed; Gordon, Jeffrey I.
Afiliação
  • Chen RY; 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
  • Kung VL; 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
  • Das S; 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
  • Hossain MS; 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
  • Hibberd MC; 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
  • Guruge J; 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
  • Mahfuz M; 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
  • Begum SMKN; 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
  • Rahman MM; 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
  • Fahim SM; 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
  • Gazi MA; 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
  • Haque R; 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
  • Sarker SA; 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
  • Mazumder RN; 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
  • Di Luccia B; 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
  • Ahsan K; 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
  • Kennedy E; 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
  • Santiago-Borges J; 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
  • Rodionov DA; 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
  • Leyn SA; 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
  • Osterman AL; 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
  • Barratt MJ; 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
  • Ahmed T; 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
  • Gordon JI; 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
N Engl J Med ; 383(4): 321-333, 2020 07 23.
Article em En | MEDLINE | ID: mdl-32706533
ABSTRACT

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. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Etiology_studies Limite: Animals / Female / Humans / Infant / Male País/Região como assunto: Asia Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Etiology_studies Limite: Animals / Female / Humans / Infant / Male País/Região como assunto: Asia Idioma: En Ano de publicação: 2020 Tipo de documento: Article