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

Science. 2023 Feb 24;379(6634):826-833. doi: 10.1126/science.ade9767. Epub 2023 Feb 23.

Abstract

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.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Acetylmuramyl-Alanyl-Isoglutamine / therapeutic use
  • Animals
  • Cell Wall / chemistry
  • Epithelial Cells / microbiology
  • Epithelial Cells / physiology
  • Gastrointestinal Microbiome* / physiology
  • Germ-Free Life
  • Growth Disorders / physiopathology
  • Growth Disorders / therapy
  • Growth* / drug effects
  • Growth* / physiology
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology
  • Intestines* / microbiology
  • Intestines* / physiology
  • Lactobacillaceae* / physiology
  • Malnutrition* / physiopathology
  • Malnutrition* / therapy
  • Mice
  • Nod2 Signaling Adaptor Protein* / metabolism

Substances

  • Insulin
  • Insulin-Like Growth Factor I
  • Nod2 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Acetylmuramyl-Alanyl-Isoglutamine
  • mifamurtide