Vaginal microbiota transfer ameliorates cesarean-associated neurodevelopmental deficits in mice via N-bc2S1P synthesis on neonatal skin

 Highlights

  • •
    VMT restores skin N-bc2S1P linked to early neurodevelopment in cesarean-born neonates
  • •
    N-bc2S1P engages β-arrestin1-biased S1PR2 signaling in forebrain excitatory neurons
  • •
    β-arrestin1-biased S1PR2 signaling recruits AP-1/CBP to increase Notch H3K27ac
  • •
    Engineered S. epidermidis sustains N-bc2S1P and extends rescue of CS-associated deficits

Summary

Cesarean section (CS) bypasses neonatal exposure to maternal vaginal microbiota, leaving the metabolic contribution of skin microbiota to neurodevelopment unclear. In CS neonates receiving vaginal microbiota transfer, skin multi-omics at 24 h identified restoration of β-carboline-sphingosine-1-phosphate (N-bc2S1P), whose levels correlated with ASQ-3 scores at 3 and 6 months. In mice, N-bc2S1P assembled on neonatal skin by Lactobacillus crispatus and Bacteroides fragilis reaches the brain and selectively triggers β-arrestin1-biased S1PR2 signaling in forebrain excitatory neurons. This pathway promotes AP-1/CBP recruitment, increases H3K27 acetylation at Notch loci, and transiently ameliorates CS-associated early-life neurodevelopmental impairments. Because N-bc2S1P is rapidly cleared, we engineered the skin commensal Staphylococcus epidermidis to co-synthesize β-carboline and S1P, sustaining cutaneous N-bc2S1P production, prolonging brain exposure, and improving neurodevelopmental outcomes. These findings identify a microbe-derived, arrestin-biased S1PR2 agonist and show that engineered skin commensals extend transient maternal microbial signals into more durable neurodevelopmental benefit in mice.

Read full article at:
https://www.sciencedirect.com/science/article/abs/pii/S1931312826001319





Popular posts from this blog

Salivary microbiome diversity is associated with oral health and disease

Image
The oral microbiome is a complex community of bacteria, fungi, and viruses that inhabit the oral cavity. Microbes of the oral microbiome are implicated in health and disease. We collected 220 unstimulated saliva samples from patients with periodontal disease and varying degrees of dental caries, as well as from subjects with no signs of oral disease. Metagenomic analysis of saliva revealed significantly higher abundance of periodontal pathogens in people with gum disease, and significantly higher abundance of cariogenic species in people with dental caries. We also found that salivary microbiome diversity was significantly higher in people with periodontal disease, but not in those with only caries. Furthermore, oral microbiome diversity is affected by oral hygiene habits such as flossing frequency, but not brushing frequency. Clustering and differential analysis allowed us to identify specific commensal species, such as  Prevotella pallens and Veillonella atypica , which are signi...
Read more

Pacific has one of most successful years for grants in school history

Image
University of the Pacific secured 62 grants from federal, state and county agencies totaling more than $36 million—one of the best years for government grants in school history. The dramatic increase in fiscal year 2023—double the amount awarded to Pacific in 2022—was largely driven by three of the university’s largest grants, which include $6 million for the School of Health Sciences to  expand the social work program , $5.6 million for Benerd College to  support mental health services in K-12 schools  and $5 million to McGeorge School of Law to  improve mental health services in California . This was the best year for grants at Pacific in 15 years. “This is a reflection of the exceptional work our faculty are doing to address pressing issues,” said David Ojcius, assistant provost for research and scholarship. “These grants will have a significant impact on the community.”   Read full article at: https://www.pacific.edu/pacific-newsroom/pacific-has-on...
Read more