Gut bacteria and genetic risk for RA16 April 2024 by Paz Garcia and Isabelle Granville Smith A group of gut bacteria is linked with high genetic risk of rheumatoid arthritis (RA), according to new TwinsUK research. These findings will help researchers understand how RA may develop in the very early stages. RA is a long-term condition that causes swelling and stiffness in the joints and can lead to disability. It affects around 400,000 people in the UK. We know from previous research that certain genes can make some people are more likely to develop RA than others, and that a combination of genetic and environmental factors lead to RA. In this study, Professor Frances Williams and her pain research team at the Department of Twin Research and Genetic Epidemiology, King’s College London investigated whether high-risk genes were linked with certain types of gut bacteria. The researchers analysed genetic and microbiome data of 1,650 TwinsUK participants with no history of RA, so that they could see if they could spot any early warning signs before the onset of symptoms. The team calculated the twins’ genetic risk for RA and then looked at the gut bacteria identified from stool samples. Genes largely determine how the immune system behaves. The researchers proposed that the immune system then responds inappropriately to certain bacteria in the body, which ultimately leads to the immune system mistakenly attacking the joints. The way the immune system and our genes interact with oral and gut bacteria appears to influence the development of RA. The team found that bacteria from a group named Prevotella were associated with high genetic risk of RA. In addition, the researchers found bacteria from the same group were linked with early stages of RA when they analysed data from participants in another cohort study. These findings may one day help us predict who is likely to develop RA and prevent and treat the condition earlier and in new ways. First author Philippa Wells explained: “Our findings are in agreement with the gut microbiome having a role in the development of RA. Speculatively, in the future this could be a possible target for treating the condition. This is something future studies will need to explore.” “These methods let us investigate what is happening with the microbiome before onset of rheumatoid arthritis, as well as unpicking what influences the microbiome differences we see in people with RA. “From that, we can gain insight into the direction of influence, i.e., whether changes in the microbiome cause rheumatoid arthritis or vice versa and get a clearer idea of the underlying biology. What does this mean? In the future, we may be able to use the microbiome to predict whether and when someone might develop RA. Researchers could also develop treatment strategies for the condition that work through targeting bacteria in the body. The work was funded by the charity Versus Arthritis. Wells et al. Associations between gut microbiota and genetic risk for rheumatoid arthritis in the absence of disease: a cross-sectional study. Lancet Rheumatology, 2020.