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Gut bugs and arthritis

Hippocrates said “all disease begins in the gut”, which might be close to the truth. This research looked at a type of gut bacteria that may help protect against rheumatoid arthritis

Study under review: Human Gut-Derived Prevotella histicola Suppresses Inflammatory Arthritis in Humanized Mice.

Introduction

Rheumatoid arthritis is an inflammatory disease of the joints, often leading to pain, swelling, stiffness, and a loss of joint function. It has been estimated[1] that 1.3 million U.S. adults suffer from rheumatoid arthritis, with the disease being more common among older adults.

What makes rheumatoid arthritis unique from other forms of arthritis is that it is an autoimmune disease, just like celiac disease or type 1 diabetes. As the disease progresses, the body’s own immune system attacks the joint tissue, leading to damaged cartilage and bone tissue as well as weakened muscles, ligaments, and tendons in the surrounding area. Ultimately, this inflammatory autoimmune attack may lead to disability and a reduced quality of life[2] if left untreated.

As with other autoimmune diseases, rheumatoid arthritis has a strong genetic component that revolves around the human leukocyte antigen (HLA) complex. As shown in Figure 1, The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as bacteria. Within the HLA complex lies a set of DQ genes that code for specific proteins that sit on the surface of certain immune cells. These proteins are responsible for attaching to protein fragments outside the cell so that they may be presented to the immune system. If the immune system recognizes the fragment as foreign, it triggers a response to attack any cells of compounds in the body that carry the same fragment.

Figure 1: Antigen presentation

Several autoimmune disorders, including celiac disease and type-1 diabetes, have been associated with variations in the HLA-DQ genes that lead to the immune system falsely believing some aspect of the body is foreign. Thus, it attacks itself (villi of the small intestine in celiac disease, and the pancreatic beta-cells in type-1 diabetes).

Although one study[3] has suggested an association between HLA-DQ genes and rheumatoid arthritis development, another study[4] has failed to support this finding. Still, a third study[5] has suggested that HLA-DQ genes may affect the clinical expression of rheumatoid arthritis in humans, and transgenic[6] mouse[7] models[8] expressing this mutation (DQ8 mice) develop an inflammatory arthritis similar to rheumatoid arthritis when immunized with type-II collagen. Since rheumatoid arthritis is an autoimmune condition in which the immune system believes that collagen protein is foreign and therefore attacks it, DQ8 mice that develop arthritis upon exposure to type-II collagen provide strong support for a link between the HLA-DQ8 genes and rheumatoid arthritis development.

Another important aspect of rheumatoid arthritis appears to be the gut microbiome, with numerous studies suggesting that a dysbiotic microbiome[9][10] may be present. For instance, a previous analysis[11] of the microbiome of patients with rheumatoid arthritis revealed significantly fewer Bifidobacterium and bacteria of the Bacteroides-Porphyromonas-Prevotella group, B. fragilis subgroup, and the Eubacterium rectale-Clostridium coccoides group than the fecal microbiota of patients with fibromyalgia (a chronic disease that isn’t necessarily inflammatory). Similar alterations[12] in the gut microbiome have been observed in the aforementioned DQ8 mice as well.

However, not all studies support these findings. One study[13] reported that patients with rheumatoid arthritis had an overabundance of Prevotella copri compared to healthy individuals. Additionally, colonization of germ-free mice with this bacterium resulted in an enhanced susceptibility to chemically induced colitis.

Recently, a group of researchers from the Mayo Clinic obtained a patent for the bacteria Prevotella histicola[14], based on preliminary research suggesting that P. histicola is able to reduce disease symptoms in an animal model of multiple sclerosis. This was accomplished in part through interactions with the immune system and a reduction of inflammatory cytokines, both of which play an active role in rheumatoid arthritis. However, there is no research investigating P. histicola’s effect on rheumatoid arthritis. The current study investigated if P. histicola could affect the systemic and gut-specific immune response in an animal model of rheumatoid arthritis and whether this would translate into material changes in arthritic symptoms.

Rheumatoid arthritis is an inflammatory autoimmune disease of the joints associated with a dysbiosis of the gut microbiome. There is preliminary research showing that the bacteria P. histicola may suppress inflammation through its interactions with the immune system. The current study sought to investigate whether these benefits may be observed in an animal model of rheumatoid arthritis.

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