Crohn’s disease, an autoimmune disorder, affects more than half a million Americans and causes symptoms such as diarrhea, abdominal pain, weight loss and fatigue. Up to a third of patients may experience joint inflammation, although the reasons for this are not entirely clear. Normally, the gut lining acts as a barrier, keeping bacteria confined to the intestines. In people with Crohn’s disease and spondyloarthritis, this barrier may be compromised and lead to immune cell responses to specific gut bacteria associated with joint inflammation. According to new study by Weill Cornell Medicine researchers, people with Crohn’s disease and related joint inflammation linked to immune system dysfunction have distinct gut bacteria or microbiota, with the bacterium Mediterraneibacter gnavus (formerly Ruminococcus gnavus) being a potential biomarker.
Increased IgA coating of Escherichia coli in Crohn-SpA identified a mechanistic role for adherent-invasive E. coli in shaping mucosal immunity in SpA. In addition, the studies identified distinct alterations in Mediterraneibacter gnavus, Dialister and Parabacteroides as enriched in the microbiome of individuals with HLA-B27-associated ankylosing spondylitis (ANS) compared to those without ANS including individuals with inflammatory bowel disease. HLA-B27 status was further identified as a significant contributor to microbiome composition in these patients. Previous studies of ANS included limited numbers of HLA-B27-negative individuals with Crohn disease, and the specific compositional differences between Crohn-pSpA and Crohn-AxSpA microbiomes have been less well studied.
The present research also raises the possibility that there could be a causative link between the gut microbiota and immune cell responses that govern inflammation, because demonstrated that the gut microbiota of people with Crohn’s and axial spondyloarthritis, which is joint inflammation of the spine and lower back, differs from individuals with Crohn’s and peripheral spondyloarthritis affecting other parts of the body like the knees, hips and shoulders. To explore which gut bacteria are linked to joint inflammation in Crohn’s disease, Dr. Longman and his colleagues analyzed deidentified stool samples from 106 people recruited from the Jill Roberts Center for Inflammatory Bowel Disease, one of the largest cohorts of patients that have been analyzed for this purpose.
Samples were from 44 participants with Crohn’s disease without joint inflammation, 39 with Crohn’s disease and peripheral spondyloarthritis, 14 with Crohn’s and axial spondyloarthritis, and 9 healthy controls. To gain a better understanding of the gut bacteria in these groups, Dr. Grace Maldarelli, instructor in medicine in the Division of Infectious Diseases at Weill Cornell Medicine, took serum, the clear part of the blood, from study participants and incubated it with their stool samples. She then identified bacteria that were coated with a specific type of antibody, IgG. This type of antibody circulates in the blood, can recognize potential pathogens, and can drive inflammation. She sequenced these antibody-coated bacteria to identify which ones were associated with the different study subgroups.
The research team found that IgG-coating of M. gnavus was observed in 33% of individuals with Crohn’s disease and peripheral spondyloarthritis and 29% with Crohn’s disease and axial spondyloarthritis, versus 11% in Crohn’s disease without inflammation and healthy controls. The researchers also found that participants with Crohn’s disease without joint inflammation and Crohn’s disease with peripheral spondyloarthritis had distinct gut bacteria compared with healthy controls. In addition, the gut bacteria of individuals with Crohn’s disease with axial spondyloarthritis were distinct from Crohn’s disease with peripheral spondyloarthritis. The level of IgG coating that the researchers saw in the peripheral blood also correlated with disease activity scores in patients with joint inflammation.
Mediteraneibacter gnavus has many epitopes, which are parts of the bacteria that the immune system can recognize and react to. For example, it encodes a number of proinflammatory molecules, including lipoglycan and glucorhamnan, as well as a superantigen-like protein, IbpA, which may contribute to its antigenic properties. In addition, M. gnavus also expresses strain-specific antigens capable of interacting with mucosal surface receptors. Future research may identify which epitope is responsible for causing an immune response so that scientists could target and alter this response as a potential treatment.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Maldarelli GA et al. Gut Microbes. 2025; 17(1):2464221.
Berland M et al. Arthritis Rheumatol. 2023; 75(1):41–52.
Stoll ML et al. Clin Exp Rheumatol. 2023; 41(5):1096–1104.
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