Exciting research partially funded by the Lupus Research Alliance uncovers how gut bacteria may trigger autoimmune responses in lupus patients

A groundbreaking study led by Martin Kriegel, MD, PhD, Chief of Rheumatology and Clinical Immunology at the University of Münster, Germany, has revealed that certain gut bacteria can escape the gut and stimulate harmful immune activity in lupus patients. The research, published in the prestigious journal Science Translational Medicine, sheds light on the mechanisms behind this process, demonstrating how these bacteria interact with immune cells to trigger inflammation and autoimmunity.

For lupus patients, the findings are both hopeful and promising. By identifying how gut microbes escape and incite inflammation, researchers have opened the door to developing therapies that target these specific bacterial triggers.

“Some gut microbes can escape from the gut and stimulate immune cells in lupus. How they do that in human cells was unclear,” explained Dr. Kriegel. “We discovered a particular mechanism of inflammation upon bacterial escape that can be blocked by hydroxychloroquine, a commonly used drug for lupus.”

Gut Bacteria Trigger Lupus-Associated Inflammation

The study highlights that the escaping gut bacteria, called Enterococcus gallinarum, activate Th17 immune cells, which are known for driving inflammation, and stimulate the production of IgG3 autoantibodies, which can be damaging in autoimmune disease. This chain reaction of inflammation may contribute to disease flares and the chronic immune dysregulation seen in lupus. This process occurs through a mechanism involving Toll-like receptor 8 (TLR8), a pro-inflammatory molecule critical to lupus, and Dr. Kriegel found that its activation by the bacteria can be blocked using hydroxychloroquine.

What makes this study particularly novel is its focus on how gut pathobionts interact with human immune responses—a complex challenge that researchers have struggled to address. While most studies on the gut microbiome have been limited to animal models, Dr. Kriegel’s work bridges the gap by using both animal models and cells from individuals with lupus. This dual, translational approach provides critical insights into the mechanisms linking gut bacteria to human disease.

The LRA has had a long-standing interest in the microbiome field, supporting Dr. Kriegel’s ambitious work through the Lupus Research Alliance 2022 Global Team Science Award, 2021 Lupus Insight Prize, and 2014 Lupus Innovation Award (previously called the Novel Research Grant). Dr. Kriegel noted, “Escaping gut microbes could represent future treatment targets in certain lupus patients. We think that removing such triggers someday in patients may ameliorate disease without the need to strongly suppress the immune system.”

By uncovering how gut bacteria drive autoimmune activity, this research lays the groundwork for innovative therapies that could transform the lives of people with lupus in the future.