Gene, Environment, Microbiome and Mucosal Immune Tolerance in Rheumatoid Arthritis

Anca I. Catrina; Kevin D. Deane; Jose U. Scher


Rheumatology. 2016;55(3):391-402. 

In This Article

Microbiome Physiology in Mucosal Sites

The microbiome, as defined by Joshua Lederberg, is composed of the totality of the ecological communities of symbiotic, commensal and pathogenic microorganisms (and their genomes) that literally share our body space.[33] It has been estimated that about 100 trillion microorganisms live in and on our body spaces and surfaces, outnumbering human cells by a factor of 10 and total protein-coding genes by a factor of 100. Importantly, each mucosal site harbours its own set of distinct microbial communities that exist in the unique mucosal environments.

This characterization of the human microbiome in health and disease states has been catapulted by advances in bacterial DNA-sequencing technologies.[34] In fact, fewer than 20% of bacterial species can be cultured using classical microbiological approaches. Largely due to efforts such as those of the National Institutes of Health Human Microbiome Project[35] and the European Metagenomics of the Human Intestinal Tract consortium, an almost complete catalogue of oral, airways, intestinal and skin microbial communities is now available. This characterization of bacterial communities and its biological relationship to mucosal immunology responses have led to new advances in our understanding of their role in health and disease.[36] It has also opened new fields of research suggesting that the microbiome could potentially serve as an environmental factor leading to autoimmunity and related clinical manifestations, as demonstrated by several studies in IBD, psoriasis and inflammatory arthritis.[37–39]

For the most part, however, our microbiome fulfils complementary physiological functions vital for our survival, including assisting with metabolic activity and nutrition. In addition, as discussed in more detail below, the microbiome is fundamental for the development of the mucosal immune system and defence against luminal pathogens.