Arthritis and Gut Bacteria

New research suggests that gut bacteria may very well play a role in the development of rheumatoid arthritis and also underscores the importance of gut bacteria (which outnumber human cells ten-to-one) in keeping our bodies healthy.

It's well known that the 10 to 100 trillion bacterial cells that live in the human intestinal tract (comprising the gut microbiome) help digest food, provide essential micronutrients, and keep harmful bacteria from overwhelming us. Disturbances in the gut microbiome (so-called dysbiosis) have been associated with various illnesses, such as colorectal cancer, obesity, and IBS (irritable bowel syndrome),  with a possible role, also for Alzheimer's disease and other abnormalities of the brain.


To this list, we can now add rheumatoid arthritis (RA).

Earlier this month, Jose Scher and his colleagues, in a report published in eLIFE, presented evidence (based on DNA sequencing of 16S ribosomal genes) that sufferers of newly diagnosed, as-yet-untreated RA have a gut biome that is significantly enriched in Prevotella copri, a bacterium that exists as a minority species in the normal microbiota.

Overall, 75% of new-onset untreated rheumatoid arthritis (NORA) patients had P. copri versus 11.5% for chronic, treated AR patients and 21.4% of healthy controls.

To see if the Prevotella-associated metagenome is sufficient to predispose to increased inflammatory responses, antibiotic-treated mice were colonized with P. copri by oral gavage. Analysis of DNA extracted from fecal samples two weeks post-gavage confirmed robust colonization with P. copri. Said the researchers:

In comparison to fecal DNA from mice gavaged with media alone, P. copri-colonized mice had reduced Bacteroidales and Lachnospiraceae... Consistent with a previous report of a Prevotella taxon exacerbating an inflammatory phenotype (Elinav et al., 2011), exposure of P. copri-colonized mice to 2% dextran sulfate sodium (DSS) in drinking water for 7 days resulted in more severe colitis as assessed by enhanced weight loss, worse endoscopic score, and increased epithelial damage on histological analysis when compared to littermate controls gavaged with media alone... These data suggest that a Prevotella-defined microbiome may have the propensity to support inflammation in the context of a genetically susceptible host.

It is well established that RA is a multifactorial disease that occurs in sequential phases. Typically, the disease is preceded by a prolonged period of autoimmunity (i.e., presence of circulating auto-antibodies), in a pre-clinical state that lasts many years, during which time one sees no clinical or histologic evidence of inflammatory arthritis. With the onset of clinical disease, auto-antibodies increase along with circulating pro-inflammatory cytokines. This has led to the so-called "second-event" hypothesis in RA, which proposes that an environmental factor of some kind triggers systemic joint inflammation in the context of pre-existent autoimmunity. A change in the gut microbiome (of a kind that favors Prevotella copri) might be the final triggering event.

The report by Scher et al. by no means proves a causal role for gut bacteria in development of RA, but it adds new handwriting on the wall (saying that gut bacteria may very well play a role in development of RA) and points the way to new research and/or additional prevention and treatment options (perhaps involving probiotics and/or fecal transplant technology). If nothing else, it underscores the importance of gut bacteria (which outnumber human cells ten-to-one) in keeping our bodies healthy and points up the fact that the human body is, at the end of the day, an ecosystem that (like any other ecosystem) relies on a delicate balance between competing and cooperating elements for its ongoing successful existence.

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Sequencing the genome of a particular species of an animal is important in terms of preserving genetic diversity. Future generations don't necessarily have to worry about our memory of the Canadian Lynx warping the way hearsay warped perception a long time ago.

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It is easy to see how one can look at 66,000 genomic sequences stored away as being the analogous equivalent of the Svalbard Global Seed Vault. It is a potential tool for future conservationists.

But what are the practicalities of sequencing the genome of a lynx beyond engaging with broad bioethical questions? As the animal's habitat shrinks and Earth warms, the Canadian lynx is demonstrating less genetic diversity. Cross-breeding with bobcats in some portions of the lynx's habitat also represents a challenge to the lynx's genetic makeup. The two themselves are also linked: warming climates could drive Canadian lynxes to cross-breed with bobcats.

John Organ, chief of the U.S. Geological Survey's Cooperative Fish and Wildlife units, said to MassLive that the results of the sequencing "can help us look at land conservation strategies to help maintain lynx on the landscape."

What does DNA have to do with land conservation strategies? Consider the fact that the food found in a landscape, the toxins found in a landscape, or the exposure to drugs can have an impact on genetic activity. That potential change can be transmitted down the generative line. If you know exactly how a lynx's DNA is impacted by something, then the environment they occupy can be fine-tuned to meet the needs of the lynx and any other creature that happens to inhabit that particular portion of the earth.

Given that the Trump administration is considering withdrawing protection for the Canadian lynx, a move that caught scientists by surprise, it is worth having as much information on hand as possible for those who have an interest in preserving the health of this creature—all the way down to the building blocks of a lynx's life.

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