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Home Science & Environment Medical Research

How gut bacteria might trigger autoimmune diseases like lupus

February 6, 2025
in Medical Research
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How gut bacteria might trigger autoimmune diseases like lupus
Introduction of E. gallinarum into a complex microbiota leads to systemic translocation and induction of autoantibodies. Credit: Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adj6294

Bacteria in the gut have been implicated in autoimmune diseases, like lupus, that don’t primarily affect the gastrointestinal system. But how those bacteria affect the human immune system remains unclear.

In a new study, Yale researchers show how a gut bacterium called Enterococcus gallinarum can travel outside of the gastrointestinal system and trigger an autoimmune response. The findings, researchers say, may inform new approaches for diagnosis and treatment of autoimmune diseases.

The study was published in Science Translational Medicine.

The human body hosts many different types of bacteria. These bacteria, known collectively as the body’s microbiome, play major roles in shaping human health. But sometimes bacteria native to the human microbiome can, under certain conditions, become harmful; these are called pathobionts.

E. gallinarum, a pathobiont found in the microbiome, can promote lupus, an autoimmune disease, in mouse models and has been detected in tissues outside of the gut in patients diagnosed with the disease.

For the new study, Yale researchers Noah Palm, professor of immunobiology at Yale School of Medicine (YSM), and Martin Kriegel, an associate professor adjunct at YSM, aimed to determine how E. gallinarum has these immune effects.

Palm and Kriegel are co-senior authors of the study.

Using both human cellular and mouse model approaches, the researchers found that after E. gallinarum leaves the gut (its home base) it is able to travel to lymph nodes and the liver before finally reaching the spleen. The lymph nodes and spleen are what are known as secondary lymphoid organs, which are part of the immune system and help launch immune responses. The researchers believe that it is in these organs where the bacterium triggers its widespread autoimmune effects.

T cells are a type of white blood cell that can transform into an inflammatory version called T helper 17 (TH17) cells. In the study, the researchers found that E. gallinarum induces the transformation of TH17 cells in the spleen and blood, which then push other immune cells to maturity, and those cells go on to produce autoantibodies—antibodies that attack the body rather than pathogens.

“One problem with autoimmune diseases is we don’t really know how they start,” said Kriegel, who is also a professor at the University of Münster in Germany. “But these findings help us piece together this puzzle, and we’re beginning to understand what the triggers and drivers of these diseases might be.”

The findings suggest pathobionts like E. gallinarum may serve as biomarkers for autoimmune disease risk. They may also be targets for treating the diseases.

“Maybe in the future we wouldn’t just target the immune system when treating autoimmune diseases,” said Kriegel. “We may also be able to target the triggering bacteria as well.”

More information:
Konrad Gronke et al, Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adj6294

Provided by
Yale University


Citation:
How gut bacteria might trigger autoimmune diseases like lupus (2025, February 6)
retrieved 6 February 2025
from https://medicalxpress.com/news/2025-02-gut-bacteria-trigger-autoimmune-diseases.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.



How gut bacteria might trigger autoimmune diseases like lupus
Introduction of E. gallinarum into a complex microbiota leads to systemic translocation and induction of autoantibodies. Credit: Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adj6294

Bacteria in the gut have been implicated in autoimmune diseases, like lupus, that don’t primarily affect the gastrointestinal system. But how those bacteria affect the human immune system remains unclear.

In a new study, Yale researchers show how a gut bacterium called Enterococcus gallinarum can travel outside of the gastrointestinal system and trigger an autoimmune response. The findings, researchers say, may inform new approaches for diagnosis and treatment of autoimmune diseases.

The study was published in Science Translational Medicine.

The human body hosts many different types of bacteria. These bacteria, known collectively as the body’s microbiome, play major roles in shaping human health. But sometimes bacteria native to the human microbiome can, under certain conditions, become harmful; these are called pathobionts.

E. gallinarum, a pathobiont found in the microbiome, can promote lupus, an autoimmune disease, in mouse models and has been detected in tissues outside of the gut in patients diagnosed with the disease.

For the new study, Yale researchers Noah Palm, professor of immunobiology at Yale School of Medicine (YSM), and Martin Kriegel, an associate professor adjunct at YSM, aimed to determine how E. gallinarum has these immune effects.

Palm and Kriegel are co-senior authors of the study.

Using both human cellular and mouse model approaches, the researchers found that after E. gallinarum leaves the gut (its home base) it is able to travel to lymph nodes and the liver before finally reaching the spleen. The lymph nodes and spleen are what are known as secondary lymphoid organs, which are part of the immune system and help launch immune responses. The researchers believe that it is in these organs where the bacterium triggers its widespread autoimmune effects.

T cells are a type of white blood cell that can transform into an inflammatory version called T helper 17 (TH17) cells. In the study, the researchers found that E. gallinarum induces the transformation of TH17 cells in the spleen and blood, which then push other immune cells to maturity, and those cells go on to produce autoantibodies—antibodies that attack the body rather than pathogens.

“One problem with autoimmune diseases is we don’t really know how they start,” said Kriegel, who is also a professor at the University of Münster in Germany. “But these findings help us piece together this puzzle, and we’re beginning to understand what the triggers and drivers of these diseases might be.”

The findings suggest pathobionts like E. gallinarum may serve as biomarkers for autoimmune disease risk. They may also be targets for treating the diseases.

“Maybe in the future we wouldn’t just target the immune system when treating autoimmune diseases,” said Kriegel. “We may also be able to target the triggering bacteria as well.”

More information:
Konrad Gronke et al, Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adj6294

Provided by
Yale University


Citation:
How gut bacteria might trigger autoimmune diseases like lupus (2025, February 6)
retrieved 6 February 2025
from https://medicalxpress.com/news/2025-02-gut-bacteria-trigger-autoimmune-diseases.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.


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