S. Tankou

Icahn School of Medicine at Mount Sinai Neurology

Author Of 1 Presentation

Microbiome Oral Presentation

PS10.04 - Effect of vancomycin on intestinal permeability during experimental autoimmune encephalomyelitis

Speakers
Presentation Number
PS10.04
Presentation Topic
Microbiome
Lecture Time
09:57 - 10:09

Abstract

Background

Two studies have reported increased intestinal permeability in multiple sclerosis (MS) patients. Other studies have observed increased intestinal permeability during experimental autoimmune encephalomyelitis (EAE). However, the mechanisms for increased intestinal permeability during EAE/MS remain poorly understood.

Objectives

Since trypsin regulates gut permeability via activation of proteinase activated receptor 2 (PAR2), the goal of this study is to investigate stool trypsin activity during EAE.

Methods

Stool were collected from adult C57BL/6J mice prior to EAE induction as well as at several time points post EAE induction. Stool trypsin activity was measured at time points of interest. Terminal ileum was collected from naïve and EAE mice to examine PAR2 expression. To investigate the role of the gut microbiota on gut trypsin activity during EAE, we induced EAE in mice receiving water or vancomycin. Next, germ-free (GF) mice were colonized with either control mice microbiota or microbiota from vancomycin treated mice and EAE was induced. Feces were collected from the colonized GF mice on the day of EAE induction.

Results

We did not observe change in stool trypsin activity during EAE in untreated mice. We found a 1.5 fold increased in PAR2 expression in the ileum of untreated EAE mice. We found that vancomycin treatment ameliorates EAE. GF mice colonized with microbiota from vancomycin treated mice developed less severe disease than GF mice colonized with feces from control mice. Unlike control mice, vancomycin treated mice had an intact intestinal permeability during EAE. In addition, stool trypsin activity was decreased in vancomycin treated mice during EAE. GF mice colonized with microbiota from vancomycin treated mice had lower stool protease activity compare to GF mice colonized with control microbiota.

Conclusions

Upregulation of intestinal PAR2 drives increased gut permeability during EAE. Vancomycin treatment preserves intestinal permeability via inhibition of stool trypsin activity. Vancomycin effect on stool trypsin activity is mediated via the microbiota. Identification of communities of gut derived bacteria that modulate stool trypsin activity could lead to the development of a novel class of drugs for the prevention and treatment of MS.

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Presenter Of 1 Presentation

Microbiome Oral Presentation

PS10.04 - Effect of vancomycin on intestinal permeability during experimental autoimmune encephalomyelitis

Speakers
Presentation Number
PS10.04
Presentation Topic
Microbiome
Lecture Time
09:57 - 10:09

Abstract

Background

Two studies have reported increased intestinal permeability in multiple sclerosis (MS) patients. Other studies have observed increased intestinal permeability during experimental autoimmune encephalomyelitis (EAE). However, the mechanisms for increased intestinal permeability during EAE/MS remain poorly understood.

Objectives

Since trypsin regulates gut permeability via activation of proteinase activated receptor 2 (PAR2), the goal of this study is to investigate stool trypsin activity during EAE.

Methods

Stool were collected from adult C57BL/6J mice prior to EAE induction as well as at several time points post EAE induction. Stool trypsin activity was measured at time points of interest. Terminal ileum was collected from naïve and EAE mice to examine PAR2 expression. To investigate the role of the gut microbiota on gut trypsin activity during EAE, we induced EAE in mice receiving water or vancomycin. Next, germ-free (GF) mice were colonized with either control mice microbiota or microbiota from vancomycin treated mice and EAE was induced. Feces were collected from the colonized GF mice on the day of EAE induction.

Results

We did not observe change in stool trypsin activity during EAE in untreated mice. We found a 1.5 fold increased in PAR2 expression in the ileum of untreated EAE mice. We found that vancomycin treatment ameliorates EAE. GF mice colonized with microbiota from vancomycin treated mice developed less severe disease than GF mice colonized with feces from control mice. Unlike control mice, vancomycin treated mice had an intact intestinal permeability during EAE. In addition, stool trypsin activity was decreased in vancomycin treated mice during EAE. GF mice colonized with microbiota from vancomycin treated mice had lower stool protease activity compare to GF mice colonized with control microbiota.

Conclusions

Upregulation of intestinal PAR2 drives increased gut permeability during EAE. Vancomycin treatment preserves intestinal permeability via inhibition of stool trypsin activity. Vancomycin effect on stool trypsin activity is mediated via the microbiota. Identification of communities of gut derived bacteria that modulate stool trypsin activity could lead to the development of a novel class of drugs for the prevention and treatment of MS.

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