Microbiota-dependent Formylated Peptide Receptor (Fpr1/2) Signaling Regulates Enteric Nervous System Development and...

Area of Science:

• Immunology and Neuroscience
• Gastrointestinal Physiology
• Microbiome Research

Background:

• Formylated peptide receptors 1 and 2 (FPRs) are pattern recognition receptors involved in innate immunity.
• The role of FPRs in the development of the enteric nervous system (ENS) and gastrointestinal (GI) motility remains unexplored.
• Bacterial formylated peptides are ligands for FPRs, suggesting a link between the microbiota and gut function.

Purpose of the Study:

• To investigate the role of FPRs in ENS development and GI motility.
• To determine if maternal microbiota-FPR signaling influences embryonic ENS development.
• To explore FPRs as potential therapeutic targets for GI hypomotility disorders.

Main Methods:

• Generated mice with germline, epithelial-, and neural crest-specific deletion of the Fpr1/2 locus.
• Utilized gestational microbiota suppression and colonization models in mice.
• Assessed ENS density via immunostaining and confocal imaging; measured GI motility and fecal formylated peptides.

Main Results:

• FPR deletion in mice led to reduced ENS density and impaired GI motility.
• Antibiotic exposure during pregnancy decreased ENS density and GI motility in offspring.
• Restoring maternal microbiota during gestation improved ENS development and GI motility in offspring.

Conclusions:

• Microbiota-FPR signaling is essential for normal ENS development and GI motility in mice.
• FPRs represent a potential therapeutic target for correcting GI hypomotility.
• Prudent use of antibiotics during pregnancy is advised due to potential impacts on ENS development.