The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior

Area of Science:

• Neuroscience
• Immunology
• Microbiology
• Developmental Biology

Background:

• The gut microbiota influences brain development and behavior, but mechanisms remain unclear.
• Bacterial peptidoglycan (PGN) is a key component of bacterial cell walls.

Purpose of the Study:

• To investigate if bacterial peptidoglycan (PGN) from the gut microbiota impacts brain development.
• To identify the molecular mechanisms of gut-brain communication involving PGN.

Main Methods:

• Expression-profiling to analyze PGN-sensing molecules and transporters in the developing brain.
• Utilized germ-free and antibiotic-treated mice to manipulate gut microbiota.
• Examined PGN-recognition protein 2 (Pglyrp2) knockout mice for behavioral and gene expression changes.

Main Results:

• PGN-sensing pattern-recognition receptors (PRRs) and the PGN transporter PepT1 are expressed in the developing brain.
• Expression of these molecules in the striatum is sensitive to gut microbiota manipulation.
• Pglyrp2 knockout mice showed altered autism risk gene c-Met expression and sex-dependent social behavior changes.

Conclusions:

• Bacterial PGN can translocate to the brain and activate innate immune PRRs.
• Gut microbiota-derived PGN signaling influences brain development and behavior.
• Central PRR activation by microbial products is a potential gut-brain communication pathway.