A devastating inflammatory disease known as rheumatoid arthritis (RA) affects millions of people worldwide. The underlying cause of RA is mostly unknown. While the specific microbe (or microbes) has not been identified, researchers have long suspected that the microbiome influences how the disease develops.
Now, researchers have identified a strain of Subdoligranulum bacteria that may be responsible for the development of RA in a recent Science Translational Medicine article. Some people at risk for the disease have antibodies to this bacterium, and RA patients are more likely to have T cells activated by Subdoligranulum than healthy controls. More interestingly, mice exposed to this bacterium developed a condition similar to RA in humans.
To better understand these species, the researchers cultured bacteria from these two families of bacteria in high concentrations in a person's stool. They identified isolates 1 and 7 of Subdoligranulum bacteria as possible candidates for triggering the development of RA. In the blood of RA patients, isolate 7 was a more potent T-cell activator than isolate 1.
The scientists fed the isolate 7 bacteria to mice to see if the bacteria actually caused the disease. Kristine Kuhn, a rheumatologist at the University of Colorado and co-author of the study, said that scientists did not expect anything to happen when they gave bacteria to mice without using any other substance to activate the immune system.
According to Kuhn, we believed we had to somehow strengthen their immune system. Meagan [Chriswell, a different author] kept an eye on mice to ensure continued colonization. A few weeks later, while I was out of town, he contacted me and said, "Kristine, you'll never believe this but the rats' paws are starting to swell." This is comparable to the swollen hand and finger joints that RA patients suffer.
While other bacteria have previously been associated with human RA, Subdoligranulus is unique to date in its ability to cause RA-like symptoms in mice without the addition of further immune damage.
Beyond those visible to the naked eye, mice and human RA patients had a variety of features. According to Kuhn, similar to rheumatoid arthritis, antibodies were getting into the joints. “So we started profiling the antibodies in the serum of mice and found that many of these antibodies target the same proteins that are targeted in rheumatoid arthritis,” the researcher said.
While this study convincingly demonstrated that this strain can cause an RA-like condition in mice, Rabi Upadhyay, a medical oncologist at NYU Grossman School of Medicine who studies the microbiome, immunity, and cancer, who was not involved in this study, is only to blame Subdoligranulum. He said it may be too soon for the study because the study doesn't necessarily rule out other species.
He said it's difficult to quantify how important a role this particular isolate will play. “He might be the dominant player, which explains why they found him in the first place. However, it is possible to develop more if they go back and create larger screens; [Subdoligranulum] will then just be one of many.
In parallel, researchers discovered this Subdoligranulum strain in only 16,7% of individuals with early-stage RA or at risk of developing RA. This indicates that this strain is most likely not the only cause of the disease.
According to Upadhyay, the study is nonetheless interesting. There is currently no treatment available that can prevent or cure the disease, and immunosuppressant medications used to treat symptoms can have harmful side effects.
“The reason I think this line of research is particularly exciting is that it gets to the true onset of disease so well that we can design therapeutics to disrupt the colonization of bacteria… we can design therapeutics to disrupt the colonization of bacteria to see if you can prevent a percentage of the disease prevalence by getting rid of colonization. This will completely change the types of treatment a rheumatologist can apply.
Source: the-scientist.com/news-opinion
Günceleme: 30/04/2023 00:46