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Gut microbes trigger autoimmune disease later in life in mice

19.01.2015

Researchers have revealed that the colonization of the gut of young mice by certain types of bacteria can lead to immune responses later in life that are linked to disease.

Increases in the levels of segmented filamentous bacteria can trigger changes in the lymphoid tissue of the mouse gut that result in the production of antibodies that attack components of the cell nucleus.

This type of damage is a hallmark of autoimmune diseases like systemic lupus erythematosus and systemic sclerosis where organs throughout the body are damaged by wayward immune responses. The findings are published in The EMBO Journal.

"Our results demonstrate how gut health in young animals may be linked to autoimmune disease in older animals," says Dirk Elewaut, Professor at Ghent University Hospital in Belgium and VIB Inflammation Research Center, Ghent University, Ghent, Belgium who is one of the lead authors of the study.

"The microbiome of the young mouse impacts a loss of tolerance of the secondary immune system against proteins in the nucleus of the cell. The attack of certain proteins by the body's own immune system can subsequently lead to tissue damage and disease."

The researchers used mice in which secondary lymphoid organs were lacking for their studies. Secondary lymphoid organs include lymph nodes, tonsils, spleen and other structures where lymphocytes, the white blood cells that play essential roles in the body's immune system, are activated.

The mice were produced by interfering with lymphotoxin and Hox11, two essential proteins involved in the autoimmune response of animals. The scientists showed that approximately one quarter of mice modified in this way spontaneously developed antibodies that would attack components of the cell nucleus.

This increase in undesired, self-inflicted immune reactions was influenced by the presence of segmented filamentous bacteria in the gut of younger mice. Segmented filamentous bacteria are clostridia-related microorganisms found in the gut of many animals including mice, rats and humans.

"We have demonstrated a link between the microbiome of young mice and the later onset of autoimmune disease," says Elewaut. "Further work is needed to establish the precise molecular mechanisms that leads to the onset of diseases like systemic lupus erythematosus and systemic sclerosis in humans but we now have a new path of enquiry that we can pursue and look for potential interventions."

Commensal microbiota influence systemic autoimmune responses

Jens T. Van Praet, Erin Donovan, Inge Vanassche, Michael B. Drennan, Fien Windels, Amélie Dendooven, Liesbeth Allais, Claude A. Cuvelier, Fons van de Loo, Paula S. Norris, Andrey A. Kuglov, Sergei A. Nedospasov, Sylvie Rabot, Raul Tito, Jeroen Raes, Valerie Gaboriau-Routhiau,Nadine Cerf-Bensussan, Tom Van de Wiele, Gérard Eberl, Carl F. Ware and Dirk Elewaut

Read the paper:

The paper will be available at 12:00 noon on Monday 19th January

doi: 10.15252/embj.201489966

http://dx.doi.org/10.15252/embj.201489966

If you would like to receive a PDF of the paper during the embargo period please send an email to barry.whyte@embo.org

Further information on The EMBO Journal is available at emboj.embopress.org

Media Contacts

Barry Whyte
Head | Public Relations and Communications
barry.whyte@embo.org

Karin Dumstrei
Senior Editor, The EMBO Journal
Tel: +49 6221 8891 406
Karin.dumstrei@embo.org

About EMBO

EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.

For more information: http://www.embo.org

Barry Whyte | EurekAlert!

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