Nature(IF 69.504) 16S+metabolism+transcription reveals that intermittent fasting promotes repair of nerve damage

mouse dorsal root ganglion; mouse serum

 Technical route

Step 1: Metabolomics analysis of the effects of different dietary patterns on mice with sciatic nerve injury;

Step 2: 16S sequencing to explore the microbial factors of IPA metabolite changes;

Step 3: Validation of microbial-mediated metabolic effects with vancomycin;

Step 4: Strain infection and gavage experiments proved that IPA affects the growth of DRG neurons in mice;

Step 5: Transcriptome sequencing to mine CXCR2-mediated sciatic nerve injury repair;

Step 6: Physiological indicators reflect that IPA promotes innervation

 Research result

1.

A mouse sciatic nerve extrusion model was established, and the injured mice were treated with intermittent fasting (IF) and regular diet (AL) for 10 days, and it was observed that IF could promote axon regeneration within 72 hours

2.

Studies have shown that vancomycin can be used to treat bacterial infections

3.

16S rDNA amplicon sequencing was performed on the cecum of four groups of mice to verify the effect of vancomycin on the flora in different treatment groups

4.

To investigate whether axonal regeneration is related to the synthesis of IPA by gut microbes, the guts of mice were infected with Cs fldC strains and Cs WT strains that were incapable of producing IPA after vancomycin depleted Gram-positive bacteria in the guts of mice.

5.

RNA sequencing analysis and antibody experiments were performed on DRG in healthy mice, DRG in mice that received IPA for 10 days after sciatic nerve injury at two time points, 72 hours and 3 days, and DRG in mice administered orally with PBS

Figure 5 IPA treatment alters DRG gene expression and increases neutrophil numbers

6.
Exploring the therapeutic effect of flora metabolites: IPA promotes repair and skin innervation

To explore whether IPA can accelerate injury repair, the recovery of physiological sensory function was assessed by thermal stimulus response and mechanical pain response
.
The results showed that IPA-treated mice recovered faster from thermal injury, ie, induced sensory recovery by improving epidermal nerve distribution, but did not induce neuropathic pain
.

Figure 6 IPA accelerates damage repair and affects innervation

Xiaobian summary

In this study, a mouse model of sciatic injury was established, and different dietary methods were used to intervene and verify the interference with antibiotics
.
Using a multi-omics combined model of metabolomics + 16S + transcriptome sequencing, we demonstrated a neural regeneration mechanism that relies on intermittent fasting to modulate the microbiota, thereby producing changes in IPA metabolites
.
This study provides new therapeutic strategies for nerve injury, promoting axonal regeneration and enhancing nerve recovery
.