{"id":67615,"date":"2022-12-30T10:36:25","date_gmt":"2022-12-30T17:36:25","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=67615"},"modified":"2024-07-18T14:34:16","modified_gmt":"2024-07-18T20:34:16","slug":"new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\/","title":{"rendered":"New rheumatoid arthritis research points to bacterial strain in the gut as a disease trigger\u00a0"},"content":{"rendered":"
<\/div>
\"New
New research suggests a bacterial strain in the gut may trigger rheumatoid arthritis, an autoimmune disease that attacks the joints. Photo: Getty Images.<\/figcaption><\/figure>\n

To visualize the idea of the 80 or so autoimmune diseases that afflict some 24 million people in the United States<\/a>, consider a boxer bobbing and weaving in a ring. No visible opponent strides forth to land a blow, yet the boxer is engaged in a very real bout \u2013 with himself. He cannot emerge as a victor.<\/p>\n

The reasons why the immune systems of people with various forms of arthritis, Type 1 diabetes, lupus, multiple sclerosis and many other diseases go awry and cause the body-as-boxer to attack itself remain murky and the subject of intense investigation. Genetics, individual biomarkers, environmental exposures, and lifestyle choices are among the factors. Now researchers at the University of Colorado \u2013 Anschutz Medical Campus<\/a> have identified a new suspect: a strain of bacteria lurking in the gut that may be a trigger for rheumatoid arthritis (RA)<\/a>, an autoimmune disease that attacks the joints, causing often-severe pain and stiffness in about 1.5 million people in the U.S.<\/a><\/p>\n

The findings, published in late October in Science Translational Medicine<\/em>, focused on the moist inner lining of the intestine called the mucosa. There they searched for possible links between the jungle of gut microbes and antibodies found in people who have or are vulnerable to RA. They collected blood from people at risk for the disease and isolated the relevant disease-linked antibodies. In the lab, they demonstrated that the antibodies \u201ccross-reacted\u201d with bacteria from two families. That is, the antibodies bound to certain bacteria, creating an immune response.<\/p>\n

Studying gut bacteria and rheumatoid arthritis<\/strong><\/h2>\n
\"CU
CU Division of Rheumatology head Dr. Kristi Kuhn, senior author of the paper, believes the new finding is another step toward understanding the riddle of what triggers rheumatoid arthritis. Photo by the University of Colorado.<\/figcaption><\/figure>\n

That finding spurred further investigations and a powerful discovery. After culling bacteria from stool samples of individuals at risk for RA, the researchers isolated a new strain of bacteria, Subdoligranulum didolesgii<\/em> \u2013 more on that later \u2013 that the key antibodies targeted and bound to. Rather than eliminating the bacteria as an intruder, the antibodies launched an inflammatory attack by specific T cells, which normally help to protect the body from infections.<\/p>\n

That work showed the bacteria triggered a strong immune response in the gut. But could the reaction invade the joints? To test that, the researchers gave the Subdoligranulum didolesgii<\/em> strain orally to healthy mice. In short order, the rodents developed swollen and gnarled paws, reminiscent of the afflictions of human RA sufferers. Mice that did not receive that specific strain did not show these changes.<\/p>\n

As part of her Ph.D. work, CU Medical Scientist Training Program<\/a> student Dr. Meagan Chriswell was the lead author of the study. She cautioned that the findings, while promising, leave many questions yet to be answered about RA specifically and autoimmune disease in general. But the work sheds more light on the mysteries of the maladies, she added.<\/p>\n

\u201cThere is no presupposition on our part that [this bacteria] is the sole cause of RA,\u201d Chriswell said. \u201cThere are potentially other bacteria and other factors that could be happening biologically to drive it. However, this is the first time we have a discrete organism linked to the disease in this way. This is the beginning of a story, not the end.\u201d<\/p>\n

Others have taken note. Chriswell said she recently attended the annual meeting of the American College of Rheumatology conference<\/a> in Philadelphia, which highlighted the study as important to basic science research. The work, which included contributions from 10 other CU School of Medicine faculty from the CU School of Medicine divisions of Rheumatology and Infectious Disease and the Department of Pathology, also drew attention<\/a> from the school\u2019s Dean, Dr. John J. Reilly<\/a>.<\/p>\n

Bacteria correlations in an autoimmune disease research chain<\/strong><\/h2>\n

Far from being a stand-alone, the study is an extension of many years of work by specialists in the Division of Rheumatology on autoimmune diseases and how mucosal surfaces throughout the body \u2013 mouth, lungs, and gut among them \u2013 may be involved, said senior author and Division of Rheumatology head Dr. Kristi Kuhn<\/a>. Kuhn is a researcher in RA and other forms of arthritis and autoimmune disease who also practices in the UCHealth Rheumatology Clinic \u2013 Anschutz Medical Campus<\/a>.<\/p>\n

\"PhD
Ph.D. researcher Dr. Meagan Chriswell was lead author of recently published research implicating a new bacterial strain in triggering rheumatoid arthritis. Photo by the University of Colorado.<\/figcaption><\/figure>\n

Kuhn said research interest in the mucosa sprang in part from a connection between inflammatory bowel disease<\/a> (IBD) and spondyloarthritis<\/a>, which mainly attacks the spine but can also invade arm and leg joints, the skin and the intestines. Kuhn co-authored a 2021 article<\/a> that summarized the long-running interest and research in links between the two conditions. The paper noted that \u201csignificant numbers\u201d of patients with spondyloarthritis also have IBD and inflammation in the gut. Kuhn and her co-authors also pointed to the intestinal mucosa as an entry point for a possible \u201cenvironmental trigger\u201d for the arthritis in IBD patients.<\/p>\n

Kuhn had already published widely on evidence supporting the connections between the mucosa and the development of RA and other kinds of arthritis. These included co-authored papers released in 2016<\/a>, 2018<\/a> and 2019<\/a>. The new study, with Chriswell and colleagues, focuses on the intestinal mucosa as a thriving home for both the antibodies linked to RA and microbes that might be their targets.<\/p>\n

\u201cWe wanted to take these antibodies that have mucosal features and see if they start to [bind to] bacteria,\u201d Kuhn said. \u201cThe gut is our largest exposure to microbes.\u201d<\/p>\n

A strain with a spiritual and scientific connection<\/strong><\/h2>\n

What of this still mysterious bacterial strain, Subdoligranulum didolesgii<\/em>? Its importance is not only scientific but also cultural. Chriswell said she proposed the name as a member of the Cherokee Nation. \u201cDidolesgii\u201d is the Cherokee word for arthritis or rheumatism<\/a>. She noted that indigenous people carry a disproportionate risk for arthritis. At the same time, their scholarly and academic work has been \u201cchronically underrepresented in the literature,\u201d she added.<\/p>\n

\u201cThe [Cherokee] name is in recognition of the disease burden and an acknowledgment of the contributions through history of indigenous scholars,\u201d Chriswell said.<\/p>\n

As for science and research, the RA-bacterial connection raises many questions while pointing the way toward additional study. For example, Chriswell said the research did not find Subdoligranulum didolesgii <\/em>in the mucosa of healthy individuals, but the sample size was small and insufficient to prove its existence is unique to people at risk for RA.<\/p>\n

\u201cThe preliminary evidence suggests that it is not in healthy people, but we need larger population studies,\u201d she said.<\/p>\n

Opportunities for further study<\/strong><\/h2>\n

The nature of the new strain is also a candidate for further probing. Chriswell noted that researchers will need to \u201ctease out\u201d whether Subdoligranulum didolesgii <\/em>is a \u201ccommensal\u201d organism \u2013 one that naturally exists in people but \u201cstarts behaving badly\u201d and triggering an autoimmune response \u2013 or a response-triggering pathogen that people catch.<\/p>\n

\u201cThat is unclear and is another area of active research in the lab,\u201d Chriswell said.<\/p>\n

Kuhn said the study suggests other directions, including \u201cdrilling down to understand the mechanism of how bacteria go on to trigger the immune response.\u201d For example, does it lead the immune system to target a healthy protein in the body that looks like an invader? This reaction, dubbed \u201cmolecular memory,\u201d is the driver in patients with strep throat who contract rheumatic fever. In that disease, the immune system attacks a target that looks like the bacteria but instead interacts with a human protein in heart tissue and damages the valves. Could Subdoligranulum didolesgii <\/em>drive a similar process, leading the immune system to attack joint tissue? Alternatively, she added, could the bacteria be \u201csomehow training our immune response to be more likely to react against our own tissue?\u201d<\/p>\n

Another challenge is to define other risk factors that could spark the immune response, Kuhn said. As she put it, \u201cHow do you go from having the bacteria and being at risk to developing RA? Is it just having these bacteria or are there other environmental factors? How do we start to put these puzzle pieces together to understand the risk and the trigger point for developing the disease?\u201d She added that she and her colleagues have not ruled out the role of other bacterial strains \u2013 not only in the gut, but also the mouth, lungs and other sites \u2013 as disease-spurring culprits.<\/p>\n

A new ray of light on a mysterious process<\/strong><\/h2>\n

What does the new work portend for patients who have or are at risk for RA? Kuhn said for now treatment will remain focused on helping patients stick to effective medication regimens<\/a> and manage risk factors, such as smoking, stress and body mass index, that are within their control. But further research, she added, could identify pathways that might be modified once the disease is triggered.<\/p>\n

\u201cThe study helps us get closer to diagnosing the disease, detecting it earlier and hopefully discovering how to modify it,\u201d Kuhn said.<\/p>\n

Chriswell added that while it is \u201chard to make specific claims\u201d from the study, it did succeed in probing \u201cthe mixed community of organisms\u201d that make up the microbiome<\/a> and pulling out one \u201cthat appears to drive disease.\u201d She hopes that spurs the scientific community to further expose the biologic machinery that underlies those misery-inducing changes.<\/p>\n

Study co-author Dr. Kevin Deane<\/a>, associate professor in the CU Division of Rheumatology, called the new findings \u201ca major breakthrough in our understanding of how autoimmune disease develops.\u201d He added that Chriswell\u2019s and Kuhn\u2019s \u201cexperimental approach to use antibodies derived from humans to identify a bacterial organism that drives arthritis in an animal model should serve as a model for future studies that can explore the role of additional organisms in triggering autoimmune diseases.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

To visualize the idea of the 80 or so autoimmune diseases that afflict some 24 million people in the United States, consider a boxer bobbing and weaving in a ring. No visible opponent strides forth to land a blow, yet the boxer is engaged in a very real bout \u2013 with himself. He cannot emerge […]<\/p>\n","protected":false},"author":2143,"featured_media":67618,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[5],"tags":[4781,102],"class_list":["post-67615","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innovative-care","tag-research-in-health-care","tag-rheumatology"],"acf":[],"yoast_head":"\nNew research looks at gut bacteria as a trigger for rheumatoid arthritis - UCHealth Today<\/title>\n<meta name=\"description\" content=\"New research suggests a bacterial strain found in the gut may trigger rheumatoid arthritis, an autoimmune disease that attacks the joints.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.uchealth.org\/today\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New rheumatoid arthritis research points to bacterial strain in the gut as a disease trigger\u00a0\" \/>\n<meta property=\"og:description\" content=\"New research suggests a bacterial strain found in the gut may trigger rheumatoid arthritis, an autoimmune disease that attacks the joints.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.uchealth.org\/today\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\/\" \/>\n<meta property=\"og:site_name\" content=\"UCHealth Today\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/uchealthorg\/\" \/>\n<meta property=\"article:published_time\" content=\"2022-12-30T17:36:25+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-07-18T20:34:16+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2022\/12\/30120631\/rheumatoidarthritis.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"800\" \/>\n\t<meta property=\"og:image:height\" content=\"533\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"author\" content=\"Tyler Smith\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@uchealth\" \/>\n<meta name=\"twitter:site\" content=\"@uchealth\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Tyler Smith\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"8 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/\"},\"author\":{\"name\":\"Tyler Smith\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/#\\\/schema\\\/person\\\/98c85c0e40c4933eedcec2cd054f349d\"},\"headline\":\"New rheumatoid arthritis research points to bacterial strain in the gut as a disease trigger\u00a0\",\"datePublished\":\"2022-12-30T17:36:25+00:00\",\"dateModified\":\"2024-07-18T20:34:16+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/\"},\"wordCount\":1676,\"publisher\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/uchealth-wp-uploads.s3.amazonaws.com\\\/wp-content\\\/uploads\\\/sites\\\/6\\\/2022\\\/12\\\/30120631\\\/rheumatoidarthritis.webp\",\"keywords\":[\"Research in health care\",\"Rheumatology\"],\"articleSection\":[\"Innovative care\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/\",\"url\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/new-rheumatoid-arthritis-research-gut-bacteria-disease-trigger\\\/\",\"name\":\"New research looks at gut bacteria as a trigger for rheumatoid arthritis - 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