In this issue, Healio Rheumatology covers the expanding implications of the microbiome in autoimmune disease as the notion of the microbiome is now widespread and is heard across multiple disciplines. Nobel Laureate Joshua Lederberg has coined the microbiome “the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space.”

Leonard Calabrese

One cannot read a newspaper or magazine without being inundated with the implications of the microbiome on health and disease. While the concept that our body’s cells are vastly outnumbered by our prokaryotic brethren is now accepted, the complexities of this vast system are continuously being revealed. It now seems certain that popping a probiotic or eating yogurt will not alter the incidence or natural history of autoimmune disease. In fact, I believe the Human Microbiome Project, which was launched in 2008 with laudatory goals including stimulating research in the field, is highly reminiscent of its parent, the Human Genome Project, which in 2003 completed the sequencing of the human genome. This feat promised to provide the blueprint for health and disease. While remarkable, it scientifically has left us with a seemingly endless series of complex unanswered questions.

Disease Onset Pathogenesis

For rheumatologists, it appears clear the microbiome is in some way integral to affecting both disease onset and pathogenesis. Early work in animal models, especially using genetically manipulated gnonobiotic mice subsequently undergoing microbiomic manipulation, has clearly demonstrated the importance of the microbiome in shaping the immune response and influencing the development and course of numerous autoimmune diseases. In humans, advances in the lab, especially targeted and even metagenomic sequencing, coupled with dramatic advances in informatics, has allowed new and innovative research – some of which is highlighted in this issue.

I would like to point out two intriguing observations to support the importance and potential of microbiomics in autoimmunity as well the dramatic complexities we must hurdle to have a clearer understanding of the field. First, what are the evidence in humans that the microbiome may be a driver of autoimmunity? Consider that Finland has one of the highest incidences of type 1 diabetes in the world and studies have previously demonstrated that the microbiome of children developing the disease appear to change in a predictable way in the year preceding the disease. This observation raised the question of possible causality, yet the evidence was incomplete.

Important Study

In an important recently published study, Vatanen and colleagues compared the microbiome of children genetically at risk for type 1 diabetes in Finland and Estonia to the microbiome of children from neighboring Russia, a country and region with a dramatically lower incidence of type 1 diabetes. In this elegant prospective study, they demonstrated that the type 1 diabetes predisposed children of Finland had microbiomes skewed to Bacteroides species while the Russian children were skewed to Escherichia coli. They then demonstrated the lipopolysaccharides from these respective bacteria were differentially capable of inducing inflammation as demonstrated by the capacity of respective lipopolysaccharides moieties to stimulate nuclear factor-kappaB dependent cytokines. They subsequently demonstrated in the animal model of non-obese mice, which are predisposed to type 1 diabetes, E. coli but not Bacteroides species were capable of decreasing the incidence of type 1 diabetes, suggesting an immunologically silencing microbiota may thus preclude aspects of immune education and subsequent disease. This, of course, is all consistent with the hygiene hypothesis, which has had its ups and downs for more than 25 years. I find this comforting.