Prolonged dysbiosis and altered immunity under nutritional intervention in a physiological mouse model of severe acute malnutrition
Fanny Hidalgo-Villeda,
Matthieu Million,
Catherine Defoort,
Thomas Vannier,
Ljubica Svilar,
Margaux Lagier,
Camille Wagner,
Cynthia Arroyo-Portilla,
Lionel Chasson,
Cécilia Luciani,
Vincent Bossi,
Jean-Pierre Gorvel,
Hugues Lelouard,
Julie Tomas
Affiliations
Fanny Hidalgo-Villeda
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France; Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras; IHU-Méditerranée Infection, Marseille, France
Matthieu Million
IHU-Méditerranée Infection, Marseille, France; Ap-HM, Marseille, France
Catherine Defoort
C2VN, INRA, INSERM, Aix Marseille University, CriBioM, Marseille, France
Thomas Vannier
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Ljubica Svilar
C2VN, INRA, INSERM, Aix Marseille University, CriBioM, Marseille, France
Margaux Lagier
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Camille Wagner
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Cynthia Arroyo-Portilla
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France; Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
Lionel Chasson
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Cécilia Luciani
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Vincent Bossi
Ap-HM, Marseille, France
Jean-Pierre Gorvel
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Hugues Lelouard
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France
Julie Tomas
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France; Corresponding author
Summary: Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer’s patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.
