Rheumatology Practice Changers 2014

Bret S. Stetka, MD; Stephen A. Paget, MD

Disclosures

December 18, 2014

In This Article

The Microbiome

The human microbiome consists of about 100 trillion microbial cells, outnumbering human cells 10 to 1. Thus, it can significantly affect human physiology. For example, in healthy individuals, the microbiota provides a wide range of metabolic functions that humans lack. However, an altered microbiota is associated with such diseases as inflammatory bowel disease and probably RA, spondyloarthropathies, and other rheumatologic diseases.

Thus, studying the human microbiome is an important task that has been undertaken by such initiatives as the Human Microbiome Project and MetaHIT. At the 2014 ACR meeting, numerous studies focused on the microbiome and its role in disease pathogeneses.

One French study[12] evaluated the relationship between gut microbiota variations and disease activity in spondyloarthritis (SpA) and RA. The investigators concluded that variations were found both in SpA and RA, compared with healthy controls, that primarily correlated with disease activity. Whether such variations are a cause or a consequence of chronic joint inflammation remains to be determined.

Another study[13] focused on the possible connection between antibiotic use and the development of juvenile idiopathic arthritis. Antibiotic exposure was associated with an increased incidence of juvenile idiopathic arthritis in a dose-dependent fashion in a large pediatric population; antibiotic therapy may there fore be implicated in disease pathogenesis, perhaps mediated through alteration in the microbiome.

Moving from the arthritides to the vasculitides, a study[14] from the Cleveland Clinic looked the microbiomes of patients with inflammatory and noninflammatory thoracic aortic aneurysms (TAAs). The investigators were curious as to whether the propensity of these conditions to affect the proximal aorta suggests common pathways in pathogenesis that could include infection, abnormalities in immune tolerance or response, presence of neoantigens, or alterations in the substrate microbiome. They sought to describe the microbiome of inflammatory (giant cell arteritis and Takayasu arteritis) and noninflammatory TAAs in patients who underwent surgical reconstruction.

They concluded, interestingly, that TAAs are not sterile. Specimens from patients with different disease associations host distinct microbial communities. Further analysis is needed to assess whether differences in microbial communities play etiologic roles or are secondary results of different types of aortic injury.

Many patients these days are aware of the potential importance of the microbiome and are taking probiotics. The studies noted above and other seminal studies done at New York University have demonstrated compelling evidence of connections between the flora in our mouths, intestines, and elsewhere with obesity and also with rheumatologic disorders, such as RA, the arthritis associated with inflammatory bowel disease, and the spondyloarthropathies. How this concept will translate into treatment opportunities remains to be seen but is likely to evolve quickly.

One biome-based therapy—fecal transplantation—is catching on quickly, perhaps surprisingly so given what it entails. Fecal transplants have been found to be nearly twice as effective as antibiotics in treating patients with recurring Clostridium difficile infection; however, the FDA has grappled with how to regulate this approach. In early 2013, the agency announced that it would treat them as biologic drugs requiring an Investigational New Drug application, which typically precedes a clinical trial.

Will rheumatologists someday be using such treatments as the sole option in our diseases, or as part of combination treatment? It is of interest that we continue to heavily immunosuppress these disorders when their origin may, in part or wholly, be due to bacteria.

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