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Updated: Jul 12, 2025
Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE
Paola Bianchimano1,2,3, Kacper Iwanowski1,2,3, Emma M Smith1,2,3
1Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract:
Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific Lactobacilli and ameliorating disease during EAE. Furthermore, Lactobacilli enriched in the gut of vancomycin-treated EAE mice at day 3 post immunization negatively correlated with gut trypsin activity and EAE severity. In untreated EAE mice, we observed increased intestinal permeability and increased intestinal protease activated receptor 2 (PAR2) expression at day 3 post immunization. Prior studies have shown that trypsin increases intestinal permeability by activating PAR2. Our results suggest that the interaction between intestinal PAR2 and trypsin may be a key modulator of intestinal permeability and disease severity during EAE.
Insights
Vancomycin treatment improved gut barrier integrity and reduced disease severity in a multiple sclerosis model by suppressing gut trypsin activity and increasing beneficial Lactobacilli. This suggests a link between gut trypsin, intestinal permeability, and neuroinflammation.
Area of Science:
- Neuroimmunology
- Gastroenterology
- Microbiome Research
Background:
- Increased intestinal permeability is observed in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).
- The precise mechanisms linking gut barrier dysfunction to neuroinflammation in EAE remain largely unknown.
Purpose of the Study:
- To investigate the role of gut trypsin activity and intestinal permeability in modulating neuroinflammation during EAE.
- To explore the therapeutic potential of vancomycin in preserving intestinal barrier integrity and ameliorating EAE.
Main Methods:
- Administration of vancomycin to EAE mice to assess its effects on intestinal barrier integrity, gut trypsin activity, and gut microbiota composition.
- Correlation analysis between Lactobacilli abundance, gut trypsin activity, and EAE severity.
- Measurement of intestinal permeability and protease activated receptor 2 (PAR2) expression in EAE mice.
Main Results:
- Vancomycin treatment preserved intestinal barrier integrity, reduced gut trypsin activity, and increased the abundance of specific Lactobacilli species.
- Lactobacilli enrichment in vancomycin-treated mice correlated negatively with gut trypsin activity and EAE severity.
- Untreated EAE mice exhibited increased intestinal permeability and elevated PAR2 expression, suggesting trypsin-PAR2 pathway involvement.
Conclusions:
- The interaction between gut trypsin and PAR2 in the intestine appears to be a critical factor influencing intestinal permeability and EAE severity.
- Targeting gut trypsin activity and modulating the gut microbiome may represent a promising therapeutic strategy for MS.
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