Contributed by Philippe J. Sansonetti, July 16, 2018 (sent for review April 16, 2018; reviewed by Dusko Ehrlich and François Leulier)
Stunting globally affects an estimated 155 million children under 5 years of age, representing about 25% of children worldwide. Due to poor understanding of the underlying pathophysiology, therapeutic interventions to efficiently correct for linear growth delay or associated pathophysiological disturbances are still lacking. Here, we describe the microbial composition of duodenal fluids from stunted children. We show that these children are affected by small intestinal bacterial overgrowth and harbor a characteristic microbial community composed mainly of oropharyngeal bacteria. This microbial signature is also reflected in their feces and conserved between countries. Stunting is traditionally considered to arise from recurrent enteric infections. This study shows that oropharyngeal taxa are associated with stunting, suggesting that alternative pathophysiological mechanisms are involved.
Linear growth delay (stunting) affects roughly 155 million children under the age of 5 years worldwide. Treatment has been limited by a lack of understanding of the underlying pathophysiological mechanisms. Stunting is most likely associated with changes in the microbial community of the small intestine, a compartment vital for digestion and nutrient absorption. Efforts to better understand the pathophysiology have been hampered by difficulty of access to small intestinal fluids. Here, we describe the microbial community found in the upper gastrointestinal tract of stunted children aged 2–5 y living in sub-Saharan Africa. We studied 46 duodenal and 57 gastric samples from stunted children, as well as 404 fecal samples from stunted and nonstunted children living in Bangui, Central African Republic, and in Antananarivo, Madagascar, using 16S Illumina Amplicon sequencing and semiquantitative culture methods. The vast majority of the stunted children showed small intestinal bacterial overgrowth dominated by bacteria that normally reside in the oropharyngeal cavity. There was an overrepresentation of oral bacteria in fecal samples of stunted children, opening the way for developing noninvasive diagnostic markers. In addition, Escherichia coli/Shigella sp. and Campylobacter sp. were found to be more prevalent in stunted children, while Clostridia, well-known butyrate producers, were reduced. Our data suggest that stunting is associated with a microbiome “decompartmentalization” of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.
↵1B.B.F., P.-A.R., and L.W.P. contributed equally to this work.
↵3A complete list of The Afribiota Investigators can be found in the SI Appendix.
Author contributions: P.V. and P.J.S. designed research; P.V., L.A., H.S., J.-R.M., F.M., and The Afribiota Investigators performed research; T.N., B.P.G., S.N.N., S.S.V., J.E.K.K., R.R., M.R., S.G.D., J.-C.G., B.B.F., and P.-A.R. supervised analyses and sample acquisition; P.V. cocoordinated the study; K.E.H. contributed her expertise on microbiota analysis; T.N., B.P.G., S.N.N., and S.S.V. performed duodenal aspirations; J.E.K.K. coordinated sample acquisition in the Central African Republic; R.R. supervised clinical aspects of the study in Madagascar; M.R. coordinated sample acquisition in Madagascar; S.G.D. supervised sample acquisition in the Central African Republic; J.-C.G. supervised clinical aspects of the study in the Central African Republic; B.B.F. provided his expertise on microbiota analysis; P.V. and P.-A.R. cosupervised small intestinal bacterial overgrowth (SIBO) analysis in the Central African Republic; L.W.P. supervised bioinformatic and biostatistic data analysis; J.-M.C. supervised SIBO analysis in Madagascar; P.J.S. cocoordinated the study and supervised the work of the first author; P.V., E.M., and L.W.P. analyzed data; and P.V., K.E.H., J.-M.C., and P.J.S. wrote the paper.
Reviewers: D.E., Institut National de la Recherche Agronomique; and F.L., Centre National de la Recherche Scientifique.
The authors declare no conflict of interest.
Data deposition: Sequence reads have been deposited in the European Nucleotide Archive, https://www.ebi.ac.uk/ena/ [accession nos. PRJEB27868 and ERP110005 (ERS2620873–ERS2621413)].
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1806573115/-/DCSupplemental.
Published under the PNAS license.
