High income countries are undergoing a massive increase in chronic inflammatory disorders, at least partly due to a failure of immunoregulation. A review in PNAS from Prof Graham Rook at UCLH explores how exposure to the “right” microorganisms (so called ‘old friends’) is crucial for the development of an effective immune system.
Early microbial exposures teach the body how to differentiate friend and foe, fundamentally affect the development of the crucial gut microbiome and prime the development of a functional immune system. Without these exposures, the immune system may attack self (leading to autoimmune diseases), attack harmless airborne particles (leading to allergic disorders such as hay fever), attack gut contents (leading to inflammatory bowel disease), or not be able to turn off background inflammation (leading to cardiovascular disease).
So, what are the most useful early microbial exposures to prime the immune system? The “hygiene hypothesis” suggests that we are ‘too clean for our own good’. However, Dr Rook suggests that exposures to a diverse group of our microbiological ‘old friends’ is what the immune system needs to develop properly, not indiscriminate microbial exposure, which will result in unnecessary exposure to harmful pathogens. Exposure to some of our ‘old friends’ (such as the worm-like parasitic helmiths) has been lost altogether in developed countries, and exposure to other microorganisms has been changed fundamentally by our urban living. Put another way, we should not allow our children to lick the toilet bowl, but should not discourage them from eating a bit of soil occasionally!
Where could this lead? Perhaps we could develop synthetic ‘crapsules’ to augment microbially deficient youngsters (in the same way that vitamin D supplements can be useful)? Or maybe the careful administration of our worm-like parasite old friends (helminths) would help to halt the progression or even reverse the course of previously incurable diseases (such as multiple sclerosis)?
I love the description of a newborn human as a computer loaded with programs (genetics) but no data, and that the type of data entered will affect how the computer functions. Also, the idea that our limited understanding of the depth, breadth and complexity of the microbial world based on the microbes we can grow in the lab can be likened to ‘microbial dark matter’. Notwithstanding the substantial gaps in our understanding, it seems that exposure to our microbial ‘old friends’ early in life is the best way to reverse the worrying trend in chronic inflammatory disorders for future generations.
Photo credit: Jay Reimer.