EMBO: 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:
doi: 10.15252/embj.201489966