Gut Bacteria can Cause, Predict and Prevent Rheumatoid Arthritis

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Collinsella aerofaciens enhances arthritis severity. Two weeks post-immunization (marked with arrow) a subset of mice were treated with C. aerofaciens every alternate day for 4 weeks (marked with arrows), n = 10. Mice not treated with C. aerofaciens (n = 8) were used as a control. Mice were followed for a incidence and onset of arthritis (*P = 0.068) and b disease severity. Collinsella enhances T-cell proliferation. c T-cell proliferation was measured by culturing sorted (by fluorescence-activated cell sorting) CD4 cells from the spleens of CII-primed mice cultured with dendritic cells that were pre-cultured with Collinsella for 4 h. **P = 0.02 (n = 3 mice/group). Collinsella reduces the expression of the tight junction protein ZO-1 and Occludin. d CACO-2 cells cultured with or without Collinsella stained with ZO-1 and Occludin showed differences in the expression of tight junction proteins. e Quantification of the mean fluorescence intensity of ZO-1 and Occludin expression in CACO-2 cells cultured alone or in the presence of Collinsella, # P < 0.05 and *P < 0.01. f Increased gut permeability was observed in DQ8 mice when Collinsella was administered. Sera of mice were tested for FITC-Dextran before and after treating mice with Collinsella for 3 weeks (*P = 0.03; n = 10 mice/group). g Fold difference in the expression of Th17 regulatory cytokine/chemokine transcripts in CACO-2 cells cultured with C. aerofaciens compared with CACO-2 cells cultured with bacterial growth media. Error bars represent standard error of the mean values. Experiments were repeated for reproducibility

Collinsella aerofaciens enhances arthritis severity. Two weeks post-immunization (marked with arrow) a subset of mice were treated with C. aerofaciens every alternate day for 4 weeks (marked with arrows), n = 10. Mice not treated with C. aerofaciens (n = 8) were used as a control. Mice were followed for a incidence and onset of arthritis (*P = 0.068) and b disease severity. Collinsella enhances T-cell proliferation. c T-cell proliferation was measured by culturing sorted (by fluorescence-activated cell sorting) CD4 cells from the spleens of CII-primed mice cultured with dendritic cells that were pre-cultured with Collinsella for 4 h. **P = 0.02 (n = 3 mice/group). Collinsella reduces the expression of the tight junction protein ZO-1 and Occludin. d CACO-2 cells cultured with or without Collinsella stained with ZO-1 and Occludin showed differences in the expression of tight junction proteins. e Quantification of the mean fluorescence intensity of ZO-1 and Occludin expression in CACO-2 cells cultured alone or in the presence of Collinsella, # P < 0.05 and *P < 0.01. f Increased gut permeability was observed in DQ8 mice when Collinsella was administered. Sera of mice were tested for FITC-Dextran before and after treating mice with Collinsella for 3 weeks (*P = 0.03; n = 10 mice/group). g Fold difference in the expression of Th17 regulatory cytokine/chemokine transcripts in CACO-2 cells cultured with C. aerofaciens compared with CACO-2 cells cultured with bacterial growth media. Error bars represent standard error of the mean values. Experiments were repeated for reproducibility

The bacteria in your gut can predict susceptibility to RA, suggests Veena Taneja, Ph.D., an immunologist at Mayo Clinic’s Center for Individualized Medicine. Dr. Taneja recently published 2 studies connecting the dots between gut microbiota and rheumatoid arthritis. More than 1.5 million Americans have RA. Dr. Taneja’s team studies indicate that testing for specific microbiota in the gut can help physicians predict and prevent the onset of rheumatoid arthritis.

Prevotella histicola

Prevotella histicola

The paper in Genome Medicine summarizes a study of RA patients, their relatives and a healthy control group. It aimed to find a biomarker that predicts susceptibility. They noted an abundance of certain rare bacterial lineages causes a microbial imbalance that is found in RA patients. “Using genomic sequencing technology, we were able to pin down some gut microbes that were normally rare and of low abundance in healthy individuals, but expanded in patients with rheumatoid arthritis,” Dr. Taneja says.

Patients with RA are characterized by expansion of rare microbial lineages. a, b LefSe analysis was performed to identify differentially abundant taxa, which are highlighted on the phylogenetic tree in cladogram format (a) and for which the LDA scores are shown (b). Red and green colors indicate an increase or decrease in taxa, respectively, in the RA patients compared with controls. Among the identified taxa, the association of the genus Eggerthella was the most significant and remained significant after Bonferroni correction for multiple testing. The genus Faecalibacterium had the largest LDA score. c Representation of the relative abundances of Eggerthella and Faecalibacterium in RA patients, first-degree relatives (FDR) and healthy controls (HC). Each bar represents the abundance of a given sample. Solid and dashed lines indicate mean and median, respectively

Patients with RA are characterized by expansion of rare microbial lineages. a, b LefSe analysis was performed to identify differentially abundant taxa, which are highlighted on the phylogenetic tree in cladogram format (a) and for which the LDA scores are shown (b). Red and green colors indicate an increase or decrease in taxa, respectively, in the RA patients compared with controls. Among the identified taxa, the association of the genus Eggerthella was the most significant and remained significant after Bonferroni correction for multiple testing. The genus Faecalibacterium had the largest LDA score. c Representation of the relative abundances of Eggerthella and Faecalibacterium in RA patients, first-degree relatives (FDR) and healthy controls (HC). Each bar represents the abundance of a given sample. Solid and dashed lines indicate mean and median, respectively

Based on mouse studies, researchers found an association between the gut microbe Collinsella and the arthritis phenotype. The presence of these bacteria may lead to new ways to diagnose patients and to reduce the imbalance that causes rheumatoid arthritis before or in its early stages. Continued research could lead to preventive treatments.

The second paper in Arthritis and Rheumatology, explored another facet of gut bacteria. Dr. Taneja treated one group of arthritis-susceptible mice with a bacterium, Prevotella histicola vs a group that had no treatment. The study found that mice treated with the bacterium had decreased symptom frequency and severity, and fewer inflammatory conditions associated with rheumatoid arthritis. The treatment produced fewer side effects, such as weight gain and villous atrophy – a condition that prevents the gut from absorbing nutrients – that may be linked with other, more traditional treatments.

While human trials have not yet taken place, the mice’s immune systems and arthritis mimic humans, and shows promise for similar, positive effects. Since this bacterium is a part of healthy human gut, treatment is less likely to have side effects.

Rheumatoid arthritis is an autoimmune disorder; it occurs when the body mistakenly attacks itself. The body breaks down tissues around joints, causing swelling that can erode bone and deform the joints. The disease can damage other parts of the body, including the skin, eyes, heart, lung and blood vessels. http://newsnetwork.mayoclinic.org/discussion/study-gut-bacteria-can-cause-predict-and-prevent-rheumatoid-arthritis/
http://dx.doi.org/10.1186/s13073-016-0299-7
http://dx.doi.org/10.1002/art.39785