The holy grail of microbiota-based research is the possibility of effecting changes in the disease state through alterations in the microbiota. As alluded to earlier, this can be achieved in mouse models of inflammatory disease; however, in humans the scope of possible changes is narrowed and the changes generally would have to be initiated after development of disease. With these caveats in mind, there are four basic ways to alter the microbiota (probiotics, antibiotics, diet and fecal transplant), all of which have been tested in humans to varying degrees.
Probiotics: If there is an imbalance in the microbiota, then the instinctual response is to ingest new ones. Although this possibility is appealing conceptually, it has not panned out well as a therapeutic option for rheumatic disease. Randomized trials of probiotics in adult and pediatric SpA both failed to show any effect, and likewise, studies in RA have shown minimal if any benefit (see Table 2).26-32
There are several reasons why this might be the case. For one, none of these trials were predicated upon an understanding of which microbiota may have been deficient in the patient population. Thus, concluding that the microbiota are irrelevant to disease on the basis of the negative probiotic trials would be akin to giving up on drug therapy.
Second, to the extent that one of the predisposing factors in inflammatory arthritis is decreased diversity, taking large numbers each day of a single or small set of organisms whose a priori abundance has not even been established may not address the underlying issue.
Finally, in the context of several trillion organisms firmly embedded in their intestinal niches, it is not clear to what extent the introduction of new organisms will even alter the microbiota because this has not been assessed in these studies. Think of it as trying to board a rush-hour subway that is already bursting at the seams.
That said, there have been successes with probiotic therapy. They are widely used in the management of ulcerative colitis; these patients likely have available niches due to the inflammatory process, as well as extensive antibiotic use.33 Additionally, a recent study using the same TEDDY database mentioned above showed probiotics to be effective in at-risk children if, and only if, administered prior to 27 days of life.34 The microbiota of neonates is in a high state of flux, so effectiveness in this age group does not necessarily translate to success in older children and adults. Nevertheless, more sophisticated approaches to altering the microbiota with probiotics will likely continue to be assessed in treating rheumatic disease.
