Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models.

Autor:	Vonaesch P; Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France.; Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, 75005 France.; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, 4123 Switzerland.; Department of Fundamental Microbiology, University of Lausanne, Lausanne, 1015 Switzerland.; University of Basel, Basel, 4001, Switzerland., Araújo JR; Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France.; Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, 75005 France., Gody JC; Complexe Hospitalo-Universitaire Pédiatrique de Bangui, Bangui, Central African Republic., Mbecko JR; Laboratoire d'Analyse Médicale, Institut Pasteur de Bangui, Bangui, Central African Republic., Sanke H; Laboratoire d'Analyse Médicale, Institut Pasteur de Bangui, Bangui, Central African Republic., Andrianonimiadana L; Unité de Bactériologie Expérimentale, Institut Pasteur de Madagascar, Antananarivo, 101 Madagascar., Naharimanananirina T; Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona; Antananarivo, 101 Madagascar., Ningatoloum SN; Complexe Hospitalo-Universitaire Pédiatrique de Bangui, Bangui, Central African Republic., Vondo SS; Complexe Hospitalo-Universitaire Pédiatrique de Bangui, Bangui, Central African Republic., Gondje PB; Complexe Hospitalo-Universitaire Pédiatrique de Bangui, Bangui, Central African Republic., Rodriguez-Pozo A; Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France.; Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, 75005 France.; Translational Immunology Laboratory, Institut Pasteur, 75015 Paris, France., Rakotondrainipiana M; Unité d'Epidémiologie et de Recherche Clinique, Institut Pasteur de Madagascar, Antananarivo, 101 Madagascar., Kandou KJE; Laboratoire de Coprologie Fonctionnelle, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013 France., Nestoret A; Unité d'Epidémiologie, Institut Pasteur de Bangui, Bangui, Central African Republic., Kapel N; Unité d'Epidémiologie, Institut Pasteur de Bangui, Bangui, Central African Republic., Djorie SG; Laboratoire de Coprologie Fonctionnelle, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013 France., Finlay BB; Michael Smith Laboratory, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, BC V6T 1Z4 Canada., Wegener Parfrey L; Biodiversity Center, University of British Columbia, Vancouver, BC, BC V6T 1Z4 Canada., Collard JM; Complexe Hospitalo-Universitaire Pédiatrique de Bangui, Bangui, Central African Republic., Randremanana RV; Unité d'Epidémiologie et de Recherche Clinique, Institut Pasteur de Madagascar, Antananarivo, 101 Madagascar., Sansonetti PJ; Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France.; Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, 75005 France.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Oct 11; Vol. 119 (41), pp. e2209589119. Date of Electronic Publication: 2022 Oct 05.
DOI:	10.1073/pnas.2209589119
Abstrakt:	Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.
Databáze:	MEDLINE
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