Arthritis

Arthritis and Gut Bacteria

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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