Microbiome Poster Presentation

P0678 - Selected Clostridia strains increase responses related to interferon beta signaling and butyrate levels in experimental autoimmune encephalomyelitis (ID 1576)

Speakers
  • L. Calvo-Barreiro
Authors
  • L. Calvo-Barreiro
  • H. Eixarch
  • T. Cornejo
  • M. Castillo
  • L. Mestre
  • C. Guaza
  • J. González López
  • X. Montalban
  • C. Espejo
Presentation Number
P0678
Presentation Topic
Microbiome

Abstract

Background

MS patients show a significant decrease in Clostridia clusters XIVa and IV in the gut microbiome. We have previously reported that a mixture of human gut-derived 17 Clostridia strains, which belong to Clostridia clusters XIVa, IV, and XVIII, improved the clinical outcome of experimental autoimmune encephalomyelitis (EAE) mice as a therapeutic approach. The clinical improvement was related to lower histopathological signs in the central nervous system (CNS) and to an enhanced immunoregulatory response of regulatory T (Treg) cells in the periphery.

Objectives

We aimed to study in depth the mechanism of action of the treatment with Clostridia strains in Experimental Autoimmune Encephalomyelitis

Methods

In two independent experiments, myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6/J mice were treated with Clostridia strains (n=15) or vehicle (n=15) via oral gavage from 13-14 days post-immunization (dpi) until the end of the experiment (28 dpi). At 28 dpi, spleens and spinal cords were collected to perform transcriptome studies and serum was collected to determine the short-chain fatty acid (SCFA) levels. In three independent experiments, MOG-immunized C57BL6/J mice were orally gavaged with butyrate (n=19) or vehicle (n=18) from 13-15 dpi until 28 dpi. Then, spinal cords were collected to perform histopathological studies.

Results

Therapeutic administration of Clostridia strains ameliorated EAE clinical course, as previously reported. Transcriptome studies revealed increased antiinflammatory responses related to interferon beta in the periphery and lower activation, differentiation, and proliferation of immune cells in the CNS. Higher levels of the immunomodulatory SCFA butyrate were detected in the serum of Clostridia-treated mice. Therefore, we studied the therapeutic effect of butyrate on EAE. We observed a slight therapeutic impact on EAE clinical course that was connected to a noticeable improve concerning axonal damage and a tendency to lower demyelination, inflammation, and astrogliosis in the CNS.

Conclusions

Clostridia strains perform their therapeutic effect on EAE enhancing the immunoregulatory response of Treg cells and antiinflammatory responses related to interferon beta signaling pathway in the periphery. The beneficial outcome exerted by the oral administration of the 17 Clostridia strains was not exclusively related to the production of the SCFA butyrate.

Collapse