The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

CarMeN Laboratory INSERM INRAE Université Claude Bernard Lyon 1 69310 Pierre Bénite France

Genomics Core Facility European Molecular Biology Laboratory 69117 Heidelberg Germany

Institut de Génomique Fonctionnelle de Lyon Ecole Normale Supérieure de Lyon CNRS UMR5242 UCBL Lyon 1 F 69007 Lyon France

Institut Pasteur Université Paris Cité CNRS UMR6047 INSERM U1306 Biology and Genetics of the Bacterial Cell Wall Unit F 75015 Paris France

Laboratory of Gnotobiology Institute of Microbiology of the Czech Academy of Sciences 54922 Novy Hradek Czech Republic

Laboratory of Immunobiology Institute of Molecular Genetics of the Czech Academy of Sciences 14220 Prague Czech Republic

Univ Lyon Hospices Civil de Lyon Gastro enterology and Pediatric Nutrition Hôpital Femme Mere Enfant F 69500 Bron France

Université Paris Saclay INRAE AgroParisTech Micalis Institute 78350 Jouy en Josas France

University of Lille Inserm U1003 F 59000 Lille France

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$a Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice / $c M. Schwarzer, UK. Gautam, K. Makki, A. Lambert, T. Brabec, A. Joly, D. Šrůtková, P. Poinsot, T. Novotná, S. Geoffroy, P. Courtin, PP. Hermanová, RC. Matos, JJM. Landry, C. Gérard, AL. Bulteau, T. Hudcovic, H. Kozáková, D. Filipp, MP. Chapot-Chartier, M. Šinkora, N. Peretti, IG. Boneca, M. Chamaillard, H. Vidal, F. De Vadder, F. Leulier

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