“I felt myself in a solitude so frightful that I contemplated suicide. What held me back was the idea that no one, absolutely no one, would be moved by my death, that I would be even more alone in death than in life.”---Jean-Paul Sartre, La Nausea.
For many a Labor Day weekend, Jerry Lewis has told us that we will never walk alone. Mr. Sartre insists we have no choice but to walk alone. Who do we believe?
Ah, but the French did give Mr. Lewis the Legion d’honneur. Further, some recent scientific data and theories would appear to support the premise of Mr. Lewis, and that his words were, if anything, understated.
You see, we are not just not alone. We are overwhelmed. We are ravished.
We have life forms, invisible to the naked eye, living on our skin, coating our colons, occupying our airways, and hiding in our vaginas. If not an aesthetically pleasing concept, it is a powerful symbiosis: Human beings provide nutrients and a safe environment for bacteria that, in return, influence our immune system, degrade complex nutritional molecules, and produce vitamins and other essential nutritional factors.
Alone? No way. Consider that the overall number of human cells in the body is about 10 trillion. However, the total bacterial cells the human body harbors at any given time numbers approximately 100 trillion. In other words, on a cell-by-cell basis that body we call ours is only 10% human. Things become even more interesting when one considers that the human genome codes for approximately 23,000 genes, and that a growing body of literature suggests that the normal body functions require the participation of our own genes, and the genes of trillions of microorgansims that reside in and on our bodies. The genomes of the bacteria and viruses found in the human intestine are believed to encode 3.3 million genes.
Individuals no more, we are more ecosystem, where many species and their genes interact with each other in order to allow mutual survival.
A Clinical Research Conference at this year's American College of Rheumatology Annual Meeting in San Diego set out to discuss some of these issues, in the context of what might predispose a patient to developing the inflammatory disease, rheumatoid arthritis.
The term “microbiome” was coined in the year 2000 by Nobel laureate Joshua Lederberg: “The totality of ecological communities of commensal, symbiotic, and pathogenic microorganisms (and their genomes) that literally share our body space. Most of these microorganisms have been all but ignored as determinants of health and disease.” And while the molecular mechanisms responsible for, for example, the gut microbiome’s impact on metabolism and diseases throughout the body remain largely unknown, researchers are now tackling how such microorganisms impact biological functions beyond the mucosa they inhabit in order to play their respective roles in immunological, metabolic, and neurological diseases.
For example, animal models of inflammatory arthritis, a major cause of chronic pain, have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses, eliciting joint inflammation. Human rheumatoid arthritis studies have focused on different mucosal sites; and the oral microbiome, specifically the bacteria P. gingivalis, has long been implicated. Clearer disease examples of the influence of the mucosa-joint axis include spondyloarthropathies such as reactive arthritis and inflammatory bowel disease-related arthritis, jejunoileal bypass arthritis, and Whipple’s disease (in these cases the mucosa in question involves the gut).
If a distinct microbiota is identified, the next step would involve investigating whether a particular microbiome drives autoimmunity in genetically susceptible individuals. If researchers could identify pathogenic organsims in that huge human microbiome, perhaps we would derive some insights into the environmental triggers of diseases such as rheumatoid arthritis, and hopefully be led to a delineation of why such diseases develop in the first place, and perhaps gain clues to new treatments.
I and my 100 trillion roommates are sitting on the edge of our respective microbiomes in anticipation of some answers.