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Updated: Sep 9, 2025
Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice
Published on: February 3, 2016
Microbiota-dependent Formylated Peptide Receptor (Fpr1/2) Signaling Regulates Enteric Nervous System Development and
Bindu Chandrasekharan1, Huixia Wu2, Charlie Smoller2
1Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia; Department of Pediatrics, Emory University, Atlanta, Georgia.
Background & Aims:
Formylated peptide receptors 1 and 2 (Fpr1/2 or FPRs) are G-protein-coupled pattern recognition receptors that bind bacterial formylated peptides. The role of FPRs in enteric nervous system (ENS) development and gastrointestinal (GI) motility is unknown.
Methods:
We generated mice with germline, epithelial-, and neural crest-specific deletion of the Fpr1/2 locus and assessed ENS structure and GI motility. We also employed a gestational microbiota suppression model using antibiotic-treated wild-type dams, alongside a transient gestational colonization model in pregnant germ-free mice using auxotrophic Escherichia coli, to determine whether temporary restoration of maternal microbiota-Fpr1/2 signaling can regulate embryonic ENS development. Enteric neuronal density at embryonic day 18.5, postnatal day 2 (P2), and in adult mice was assessed by CLARITY immunostaining and confocal imaging of pan neuronal markers (Tuj1, HuD, and Peripherin). Fecal formylated peptide (fMLF) content was measured by mass spectrometry. GI motility was assessed by stool frequency, total GI transit time, and FITC-dextran intestinal transit assay.
Results:
Germline, epithelial, and neural crest-specific Fpr1/2 deletion resulted in reduced fetal, postnatal, and post weaning ENS density and epithelial innervation with reduced GI motility in post weaned mice. The 3-week-old pups derived from antibiotic-treated pregnant wild-type dams showed significantly reduced ENS density and GI motility, with reduced fecal fMLF. Critically, transient gestational colonization of pregnant germ-free mice with auxotrophic E. coli significantly improved enteric neuronal density and GI motility in 6-week-old offspring.
Conclusions:
Collectively our data show that microbiota-Fpr1/2 signaling in the murine gut is critical for normal ENS development and GI motility and identify Fpr1/2 as a potential therapeutic target to correct GI hypomotility. Our data also suggests a cautious approach to antibiotic usage during pregnancy.
Insights
Microbiota signaling through formylated peptide receptors (FPRs) is crucial for developing the gut
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.
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