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

Les enfants présentant un retard de croissance présentent une colonisation ectopique de l'intestin grêle par des bactéries buccales, qui provoquent une malabsorption des lipides dans des modèles expérimentaux

Pascale Vonaesch (1, 2, 3, 4) , João Araújo (1) , Jean-Chrysostome Gody (5) , Jean-Robert Mbecko (6) , Hugues Sanke (6) , Lova Andrianonimiadana (7) , Tanteliniaina Naharimanananirina (8) , Synthia Nazita Ningatoloum (5) , Sonia Sandrine Vondo (5) , Privat Bolmbaye Gondje (5) , Andre Rodriguez-Pozo (1, 9) , Maheninasy Rakotondrainipiana (10) , Kaleb Jephté Estimé Kandou (11) , Alison Nestoret (6) , Nathalie Kapel (6) , Serge Ghislain Djorie (11) , B. Brett Finlay (12) , Laura Wegener Parfrey (12) , Jean-Marc Collard (5) , Rindra Vatosoa Randremanana (10) , Philippe Sansonetti (1, 13)

1 Pathogénie microbienne moléculaire
2 Swiss Tropical and Public Health Institute [Basel]
3 UNIL - Université de Lausanne = University of Lausanne
4 Unibas - Université de Bâle = University of Basel = Basel Universität
5 Centre pédiatrique de Bangui
6 Institut Pasteur de Bangui
7 IPM - Unité de Bactériologie Expérimentale [Antananarivo, Madagascar]
8 CHUJRA - Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona
9 Immunologie Translationnelle - Translational Immunology lab
10 Institut Pasteur de Madagascar
11 CHU Pitié-Salpêtrière [AP-HP]
12 UBC - University of British Columbia
13 CdF (institution) - Collège de France

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.

Mots clés: environmental enteric dysfunction; lipid malabsorption; low-grade inflammation; small intestine; stunted child growth

Domaines: Sciences du Vivant [q-bio]; Hépatologie et Gastroentérologie

Pascale Vonaesch, João Araújo, Jean-Chrysostome Gody, Jean-Robert Mbecko, Hugues Sanke, et al.. Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (41), pp.e2209589119. ⟨10.1073/pnas.2209589119⟩. ⟨pasteur-03879197⟩