Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice

• Published in: Science (American Association for the Advancement of Science) Vol. 379; no. 6634; pp. 826 - 833
• Main Authors: Schwarzer, Martin, Gautam, Umesh Kumar, Makki, Kassem, Lambert, Anne, Brabec, Tomáš, Joly, Amélie, Šrůtková, Dagmar, Poinsot, Pierre, Novotná, Tereza, Geoffroy, Stéphanie, Courtin, Pascal, Hermanová, Petra Petr, Matos, Renata C, Landry, Jonathan J M, Gérard, Céline, Bulteau, Anne-Laure, Hudcovic, Tomáš, Kozáková, Hana, Filipp, Dominik, Chapot-Chartier, Marie-Pierre, Šinkora, Marek, Peretti, Noël, Boneca, Ivo Gomperts, Chamaillard, Mathias, Vidal, Hubert, De Vadder, Filipe, Leulier, François
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science (AAAS) 24.02.2023
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Acetylmuramyl-Alanyl-Isoglutamine - therapeutic use; Animals; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Cell Wall - chemistry; Epithelial Cells - microbiology; Epithelial Cells - physiology; Gastrointestinal Microbiome - physiology; Germ-Free Life; Growth - drug effects; Growth - physiology; Growth Disorders - physiopathology; Growth Disorders - therapy; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - physiology; Intestines - microbiology; Intestines - physiology; Lactobacillaceae - physiology; Life Sciences; Malnutrition - physiopathology; Malnutrition - therapy; Mice; Nod2 Signaling Adaptor Protein - metabolism; Acetylmuramyl-Alanyl-Isoglutamine/pharmacology/therapeutic use; Epithelial Cells/microbiology/physiology; Animals; Cell Wall/chemistry; Germ-Free Life; Insulin/metabolism; Growth Disorders/physiopathology/therapy; Mice; Insulin-Like Growth Factor I/metabolism; Intestinal Mucosa/microbiology/physiology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ade9767

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of (strain Lp ) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that Lp 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 Lp , 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 Lp -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.