Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Gut dysbiosis is associated with acceleration of lupus nephritis

We previously published about this research in a story titled “The Relationship Between Gut Bacterium and Lupus Nephritis” which can be found here. The study was originally published in the journal Scientific Reports. You can view the full text of the study here.

This research team was affiliated with The Ohio State University Wexner Medical Center and College of Medicine.

What Happened?

In recent years, a growing number of studies have begun to illustrate the relationship between the state of the gut microbiome and a variety of different diseases, such as Parkinson’s disease, multiple sclerosis, and even mental illness. The gut microbiome refers to the community of microorganisms that survive and thrive in the digestive system of human beings. These bacteria, under normal circumstances, often play a vital role in digestion, but more and more evidence suggests that they could do a whole lot more.

Few studies have been conducted in the relationship of the gut microbiome to lupus and lupus nephritis, but some early research has recognized gut microbiome dysbiosis (an imbalance of microorganisms) in patients. In this study, researchers sought to understand if changes to the microbiome could have an effect on lupus, an autoimmune disease that can cause damage to internal organs and most often impacts young women. The scientists found that the introduction of Segmental Filamentous Bacteria (SFB) to the gut of mice with lupus cause significant worsening of disease and was associated particularly with lupus nephritis, a rare complication that causes kidney damage.

Mice that had developed lupus nephritis saw the severity of the disease increase substantially. The inflammatory lesions found on these kidneys of these mice, a common characteristic of the disease, became much more active. The researchers attributed this effect to a specific effect triggered by SFB. While normally the wall of the intestine is a barrier that is relatively impermeable, SFB caused the intestinal wall to become leaky. This allows a very small amount of the intestinal contents to circulate through the rest of the body. 

SFB also had an effect on other types of bacteria that made up the mouse gut microbiome, causing an imbalance in the species composition, or dysbiosis. The scientists were driven to investigate the effect of SFB due to their impacts in rheumatoid arthritis models, another autoimmune disease. 

About Lupus Nephritis

Lupus nephritis is a medical complication characterized by kidney inflammation which can appear as a result of systemic lupus erythematosus, more commonly known as lupus. In effect it is a form of glomerulonephritis, but this form is linked specifically to lupus and has notable differences in outcomes and presentation. Lupus nephritis is an autoimmune disease in which the body’s own immune system mistakenly attacks healthy tissue. The cause of lupus and lupus nephritis is not well understood, with a variety of genetic and environmental factors possibly playing a role. Symptoms of the disease include swelling, fever, foamy urine, joint pain, high blood pressure, muscle pain, and the characteristic butterfly rash that also appears with systemic lupus. Treatment usually involves the use of immune system suppressing drugs such as corticosteroids, but when the disease progresses to kidney failure, kidney transplant is the best option. To learn more about lupus nephritis, click here.

Why Does it Matter?

The results of this research reveal a mechanism that could potentially function as a major driving force for the progression of lupus and lupus nephritis more specifically, giving the medical field vital insight. Lupus is a complex disease, and precisely how it originates is not particularly well known. However, a variety of factors, such as hormones, genetics, and environmental considerations are believed to play a role. This research has identified changes to the microbiome as one of these factors. 

“This is a major finding, because it provides a basis for future studies that will examine the effects of interventions that target the gut microbiota in the management of lupus.” – Dr. Wael Jarjour, Lead Author

The data will allow for the testing of a variety of approaches that will attempt to act on the microbiome and restore ‘balance’ to see if this causes the disease severity to improve. One approach that the scientists plan to evaluate is whether the complete elimination of SFB from the microbiome can allow lupus nephritis to improve or resolve.