Microbiome

ACR 2014: General Themes from the ACR Basic Research Conference: Emerging Perspectives on the Microbiome in Rheumatic Diseases (Nov 14-15, 2014, Boston, MA)

This was a pre-conference course with leading researchers presenting their cutting edge work on the interplay of the microbiome, immunity and disease. I’m dog tired after sitting and concentrating for hours but I want to jot down some quick thoughts on the general themes that emerged:

* Explosion of microbiome research over past 5-10 years, but its primarily at the basic science level. The immune system is complex, VERY complex. And researchers are meticulously investigating the specific mechanisms of tiny parts (one bacteria, one T cell, one cytokine) of this huge, immune system machine. These are early days, with more questions than answers regarding the impact of the microbiome on autoimmunity. And, as tempting as it is to extrapolate this data into clinical action, the science just isn’t there to back it up yet.

* Also exploding? The incidence of autoimmune diseases over the past 50 years. Genes can’t be the reason for such a big change in such a short time period, so consensus in the room is that environmental exposures underlie this epidemic. There were mentions of the impact of antibiotics, diet, and toxins but a new one for me was hearing that periodontal disease is associated with new onset rheumatoid arthritis. Aside: Interestingly, no one mentioned that 80% of the antibiotics prescribed in the USA are actually used in agriculture, so we are exposed unwittingly in our food supply.

* Studying the microbiome is complex. The microbiome composition is diverse even amongst healthy people, but further changes occur with disease, age, gender, geographic location, environmental exposures and location on the body. Even different strains of the same bacteria may have different functional impacts. And disease may be impacted not just by our own microbiome but also the microbiome of an invading organism – one study revealed that ticks with dysbiosis of their microbiome could no longer transmit Lyme disease.

* First 2-3 years of life are critical in establishing microbiome. Our microbiome is inherited from our mother at birth, shaped by our early environmental exposures, and then has a somewhat stable composition over our lifetime. But all hope is not lost if you happen to be beyond your toddler years, as this stability seems to be due to our stable lifestyle exposures rather than locked in by our biology. By changing our environmental exposures, we can change the composition of our microbiome.

* What happens in the gut, doesn’t stay in the gut. This great quote by Andrew Gerwirtz PhD, Georgia State, sums up the role of the microbiome in shaping our systemic immune response. The gut microbiome is involved in forming and training immune cells, which then move throughout the body and attack other parts of the body. Studies were presented linking the gut microbiome to autoimmune diseases as well as allergic asthma, food allergies, obesity, medication response (e.g. cyclophosphamide, acetaminophen, methotrexate), and even behavior (e.g. how much we eat, anxiety).

* The hygiene hypothesis is supported by microbiome research. We live in a sanitary world so goodbye childhood mortality from infections, hello autoimmune disease. So, get a dog, stop vacuuming and go outside. (I know, I did warn you not to jump to conclusions but this is too tempting).

* Emerging links between autoimmune diseases and specific bacteria of the microbiota. Theoretically, the microbiome was thought to play a role in autoimmunity but a direct link between one bacteria and one disease was made with the discovery of Prevotella copri predominance in new onset RA. At this time, it’s unclear whether this is a cause, and effect or simply an association.

* A lot of optimism in the room that investigating the microbiome will impact the way we understand and treat inflammatory diseases. Underlying questions include: Can we prevent specific diseases by regulating the microbiome? If so, how? Exciting prospect.

* New treatments based on microbiome work are already in the pipeline. Includes helminthes, probiotics but most promising seems to be fecal transplants, which have a great success rate for c diff infection and are being studied for a multitude of other diseases. Some research into impact of nutrition and food supply with one study looking into the impact of resistant starch on the microbiome and one on the impact of emulsifiers.

Will check back in with more specifics from this conference and the rest of ACR 2014 when I have more time.

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