Dr.ScherVideo_ RA and Microbiome

Arthritis Microbiome & Gut Health: Diet

Summary:  Arthritis… Newly diagnosed with arthritis have an arthritis microbiome that is skewed having greater abundance of the intestinal bacteria Prevotella copri than people without the inflammatory disease, or those who have had the disease for a while but were managing it with treatment. Also found: nutrient deficiencies.  Diet can change up that microbiome.  Read on and learn.

One of the first insightful articles that expanded my understanding of the connection between gut microbiome, dietary impact, and arthritis, was “The Boy With a Thorn in His Joints,” New York Times Magazine, February 2001.  Anywhere from 0.5 to 1 percent of the general population is estimated to have the condition, according to the Centers for Disease Control and Prevention.  If you are a reader of my work, you now know however, it isn’t just arthritis that the gut biome affects; literally all health and disease is affected by the gut microbiome, specifically the community of species present.

Three year old Shepard and his mom decide a life of high risk drugs was not going to happen, and Doctors Kahn and José Scher (Director of the Microbiome Center for Rheumatology and Autoimmunity-MICRA at NYU Langone Medical Center’s Hospital for Joint Diseases, and Director Arthritis Clinic NYU Hospital for Joint Disease, New York University School of Medicine) now recognize the paradigm shift connecting the gut microbiome bacterial community and arthritis.

The Arthritis Microbiome

Flash forward to today, and we learn of Dr. Scher’s latest R&D which updates the RA microbiome findings documenting the “Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis,” Scher et al., Nov 2013. 

This Huffington Post article explains the findings:  “Rheumatoid arthritis is treated with an assortment of medications, including antibiotics, anti-inflammatory drugs like steroids, and immune-suppression therapies.  Little is understood about how these medications affect gut bacteria.  “It could be that certain treatments help stabilize the balance of bacteria in the gut, or it could be that certain gut bacteria favor inflammation,” says Jose U. Scher, MD, director of the Microbiome Center for Rheumatology and Autoimmunity at NYU Langone Medical Center’s Hospital for Joint Diseases, and an author on the new study.”

“Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association,”study researcher Dan R. Littman, M.D., Ph.D., a microbiology and pathology professor at NYU, said in a statement. 

Pertinent details from the new study by Scher et al was published in the journal eLife, November 2013:  Researchers used genome sequencing to compare gut bacteria from patients with rheumatoid arthritis and healthy controls:

        • 44 fecal DNA samples from people newly diagnosed with rheumatoid arthritis who had not yet received immune-suppression treatments,
        • 26 fecal DNA samples from people with treated rheumatoid arthritis,
        • 16 fecal DNA samples from people with psoriatic arthritis (characterized by red, flaky skin in conjunction with joint inflammation), and
        • 28 fecal DNA sample from healthy people.
        • They conducted gene sequencing on the 16S gene of these samples.

Findings:  There is a marked association of the bacterial species Prevotella copri with new-onset untreated RA (NORA) patients and not with other patient groups. In other words, those newly diagnosed with rheumatoid arthritis have a greater abundance of the intestinal bacteria Prevotella copri than people without the inflammatory disease, or those who have had the disease for a while but were managing it with treatment.  Increases in Prevotella  abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects.  

The Prevalence of P. Copri Bacteria in the groups studied:  P. copri bacteria was found most in the fecal samples from the newly diagnosed patients with 75 percent of the samples carrying the bacteria.  Meanwhile, 21.4 percent of the samples from the healthy people carried the bacteria, 11.5 percent of samples from the people with treated rheumatoid arthritis carried it, and 37.5 percent of samples from people with psoriatic arthritis carried it.  

The below slides are from Dr. Jose Scher’s presentation: “The Microbiome in Rheumatoid Arthritis: Gums, Guts and Joints,” dated October, 2012 and shows the prevalence of the Pevotella species.

Prevotella High in NOVA, darker the square the higher the am

http://medicine.med.nyu.edu/education/grand-rounds/mgr-jose-scher-md-video

We also identified unique Prevotella genes that correlated with disease.  Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis.  This work identifies a potential role for P. copri in the pathogenesis of RA.

Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is unclear, the researchers say.  Both environmental influences, such as diet and genetic factors can shift bacterial populations within the gut, which may set off a systemic autoimmune attack.  Adding to the mystery, P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, the researchers found. 

“Expansion of P. copri in the intestinal microbiota exacerbates colonic inflammation in mouse models and may offer insight into the systemic autoimmune response seen in rheumatoid arthritis,” says Randy S. Longman, MD, PhD, a post-doctoral fellow in Dr. Littman’s laboratory and a gastroenterologist at Weill-Cornell, and an author on the new study. Exactly how this expansion relates to disease remains unclear even in animal models, he says.

Current treatments for rheumatoid arthritis target symptoms. However, by highlighting the role played by gut bacteria, the work of Scher et al. suggests that novel treatment options focused on curbing the spread of P. copri in the gut could delay or prevent the onset of this disease.

Also of importance, note that micronutrient insufficiency was found in the newly diagnosed NORA group:  Functional potential of the NORA metagenome (defined by an absence of functions present in Bacteroides and Clostridia, clades typically found in low abundance in Prevotella-high NORA subjects which were found here to have high P. copri bacterial species):  The resultant NORA microbiome would have a low abundance of vitamin metabolism (i.e., biotin, pyroxidal, and folate) and pentose phosphate pathway modules, consistent with a lack of these functions in  Prevotella  genomes.  The article did not address whether this deficiency persisted for the medicated study group.  

Lastly, make sure you catch the video presentation: Dr. Jose Scher, MD: “The Microbiome in Rheumatoid Arthritis: Gums, Guts, and Joints,” Oct 2012:

DrScher_RAMicrobiome
http://medicine.med.nyu.edu/education/grand-rounds/mgr-jose-scher-md-video

Here,  Dr. Scher discusses his research on the contribution of intestinal and oral microbes to the pathogenesis of rheumatologic diseases:

    1. Noting that genes are insufficient to explain the pathology in RA, Dr. Scher discusses the role of the microbiome and, specifically, the role of bacterial species (SFB) in the modulation of the human immune system in the pathogenesis of rheumatoid arthritis.
    2. Dr. Scher discusses the relationship between periodontitis and its prevalence in RA and their causal relationship concluding: PD precedes RA.
    3. Dr. Scher discusses the finding that patients with RA appear more likely to harbor specific gut flora (Prevotella rich).
    4. Dr. Scher ends with the speculation that therapy for RA in the future may be combined with therapy for periodontitis.

There you have it.  RA research is following microbiome investigations as are so many other chronic diseases.

Relative to dietary modulation and management of RA, the Chicago Tribune article, “A Gut Reaction? Rheumatoid Arthritis Has Confounded Efforts To Identify Its Trigger. Mounting Evidence Points to a New Suspect: A Disturbance in the Bacteria That Live in the Intestines,”   offers some insight.  While I must leave further discussion of this aspect for a later post, the below slide shows what protocol worked for the Walker baby, “The Boy With a Thorn in His Joints,” New York Times Magazine, February 2001, which is the article mentioned at the start of this post.  Walker’s protocol, not surprisingly, sounds a lot like PALEO, SCD, or GAPS with a nightshade twist.  It’s very similar to the Autoimmune Protocol (AIP) which makes total sense since RA is an autoimmune.

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7 thoughts on “Arthritis Microbiome & Gut Health: Diet”

  1. Don’t want to lose this: Video, “Do Autoimmune Diseases Begin in the Gut?” Dr. Stephen Paget. I am the physician-in-chief emeritus at Hospital for Special Surgery, and professor of medicine at Weill Cornell School of Medicine in New York City Dec 17, 2014. Today I am going to talk about the microbiome, an extraordinary concept that is probably not well understood by most physicians but that truly defines us as people.

    It now has become clear that the makeup of those bacteria can define whether we are healthy or have disease. What is truly extraordinary is that we now have ways to change a person’s bacterial growth and microbiome.

    Animal models of different types of arthritis have shown that an animal that lives in a germ-free environment may not develop a certain type of arthritis. As soon as the animal is moved to an environment with specific bacteria, however, those bacteria interact with the animal’s genetics and other environmental factors internally and externally to cause arthritis.

    Thus, as we learn more about autoimmune diseases and types of arthritis, we have a tremendous opportunity to make a huge difference. Some scientists have shown that periodontal bacteria may play a significant role as a stimulus for rheumatoid arthritis. Similarly, intestinal bacteria play a significant role as a cause of various types of spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis.

    This is a new world and a new age. We are coming to grips with who we are as organisms, both the organism that is visible on the outside and the organism that is inside us, with both working together in health and in disease.

    .http://www.medscape.com/viewarticle/836491

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