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
Abstract
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.