Scientists find link between bacterium in the gut ecosystem and lupus

Scientists at UT Health San Antonio, the academic health center of The University of Texas at San Antonio, found a link between a bacterium in the gut microbiome, or ecosystem, and lupus, which could lead to more effective treatment of the disease, in a study published in Nature Communications.

Systemic lupus erythematosus, the most common form of lupus, is a chronic autoimmune disease that affects approximately 1.5 million Americans. The disease has no cure and current treatments merely manage symptoms and prevent organ damage. Lupus symptoms can vary greatly, and many people spend years visiting different doctors looking for relief.

Researchers from UT San Antonio's Joe R. and Teresa Lozano Long School of Medicine found that the bacterium Faecalibacterium prausnitzii, F. prausnitzii, is depleted in the gut microbiome of lupus patients. The study showed that supplementation with the bacteria greatly reduced markers of the disease in animal models.

This is the first time in lupus research that we have identified a bacterium that is depleted and when returned, it helps."

Laurence Morel, PhD, Professor and Zachary Foundation Distinguished Chair of the Department of Microbiology, Immunology and Molecular Genetics

Morel and Yong Ge, PhD, assistant professor in the same department, headed the breakthrough study that makes the connection between the gut microbiome and lupus.

What is lupus?

Lupus is a disease in which the immune system attacks the body's healthy tissues and organs leading to inflammation of joints, skin, the brain, heart, lungs and other organs.

The current standard of care for symptom management is immunosuppressants, such as steroids. While effective, they can have side effects such as weight gain, swelling and cardiovascular complications, and can make people more susceptible to infection. In fact, a major cause of lupus mortality is infection.

Scientists have been investigating connections between the gut microbiome and lupus for about a decade. Previous research has found that the gut microbiome of lupus patients is different than that of a healthy person. At least three bacteria strains have been identified that are connected to lupus progression.

How the gut affects immune response

Prior to this current study, Ge conducted research that found F. prausnitzii enhances the ability of gut microbes to digest dietary fiber under healthy conditions.

F. prausnitzii helps reduce inflammation by producing butyrate, one of the most common short chain fatty acids. Butyrate is the main source of energy for cells lining the colon that maintain the barrier, called mucin, between the gut at the rest of the body. Butyrate is produced when "good" bacteria in the gut digest dietary fiber. When there is less F. prausnitzii, fiber is not sufficiently processed and the mucin lining breaks down.

"If you have less bacteria digesting that fiber, you have less short chain fatty acids and a more pro-inflammatory condition," said Ge.

The research team found that reintroduction of the bacteria partially restored immune regulation and also showed positive effects on the kidneys and spleen. While the exact mechanisms of the bacterium are not fully understood, Ge said it appears to have an indirect effect of modifying the microbiome by directing it to digest less mucin and more fiber, promoting better gut health.

"We were very excited that a single probiotic strain could do such big things," Ge said.

Not all probiotics are the same

Probiotics have become popular supplements, and many people include yogurt and fermented foods in their diet to aid digestive health. However, F. prausnitzii has strain-specific beneficial properties and is not in common over-the-counter probiotic products.

The bacterium is highly sensitive to oxygen and quickly becomes inactive when exposed to air. It also depletes quickly and frequent treatment is needed to maintain levels. While probiotic treatment with F. prausnitzii appears promising, further research is needed to fully understand its role in the microbiome and evaluate its benefits.

What comes next

Morel said the next step in their research will include further investigation into metabolites to discover which cell populations are associated with immune protection or inflammation. If certain metabolites have beneficial effects, this could be another path for future lupus treatments. The team is also creating studies related to the effect of diet, the microbiome and immune system.

"We want to put all of this together for a mechanistic, stringent study linking different carbohydrates in the diet with health outcomes," Morel said.