Bones and the Biome

The Link Between Our Microbiota and Rheumatologic Disease

Bret S. Stetka, MD


March 04, 2016

Editor's Note:
With our microbiota—and their collective genome, the microbiome—continually being implicated in a range of diseases, Medscape recently spoke with New York University rheumatologist Dr Jose Scher, director of the Arthritis Clinic and Microbiome Center for Rheumatology and Autoimmunity at NYU Langone Medical Center, about the influence of gastrointestinal microbes on rheumatologic disease.

A Look Back

Medscape: When did the idea develop that our microbiota might play a role in rheumatologic disease?

Jose Scher, MD: This is a very old idea. The notion that gut material has a particular link with rheumatic disease has been around for at least 100 years, if not more. This was based on something called the toxemic factor hypothesis. The whole idea was that there were enough anaerobic bacteria in the gut that produced some sort of toxic factor that, when absorbed, would cause systemic inflammation of the joints.

There are also historical data suggesting that rheumatoid arthritis is a disease that was passed from Native American tribes to European conquerors when they came in the mid-15th century. These data come from Rothschild and Woods[1] and look specifically at skeletal remains in many different museums. Essentially, what they showed was that only remains from North American populations from 2000 or 3000 years ago had erosive disease related to rheumatoid-type damage. If you now go around the world and try to find similar skeletal remains with this phenotype, you won't find it.

The literature never really described rheumatoid-type disease until the late 18th century into the 19th century, so there is no real description of the disease. Forget about calling it "rheumatoid arthritis."

All of this information combined has suggested that there is a vector that actually transmits disease.

With all of this in mind, I always give the example of sulfasalazine. In the 1940s, sulfasalazine was the first rationally designed disease-modifying antirheumatic drug for rheumatoid arthritis. The idea was to combine a sulfa antibiotic with a salicylate, to provide anti-inflammatory medication at the same time as giving an antibiotic to target gut microorganisms.

Medscape: In the past 5 or 10 years, we have seen an explosion in microbiome research. How has this influenced rheumatology?

Dr Scher: The Human Microbiome Project started grew out of a fundamental idea from Joshua Lederberg—a very important microbiologist who was a Nobel Laureate at the age of 35 years—who said that the microbiome is a totality of microorganisms in our bodies that we haven't paid enough attention to. He recognized that we have about 100 trillion microbial cells coding for about 3 million different genes, which is 100-fold higher than the human genome. They are there, and they are doing something. You can't ignore them.

These microorganisms are essentially promoting health. With them, we have coevolved over thousands of years to live peacefully. The fundamental question is: If you alter the "normal" composition of the gut microbiota, can that lead to disease? Is there a triggering event or something downstream in terms of immune properties that these microorganisms now promote?

The answer, at least from animal models, is yes. I will give you the examples that have been out there. If you keep animals that are predisposed to get arthritis under germ-free environments—no microbes whatsoever—they typically don't get disease. If you then take these animals and raise them in conventional cages where there are normal microbes, they start getting the arthritis phenotype. This is true whether it is an induced arthritis model or a spontaneous arthritis model. They have been implicated as triggering factors for inflammation of the joints.


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