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Our Complex Microbial Selves

Of all the amazing insights to come out of scientific research in the last decade, the one that holds the most personal meaning for me is the mounting evidence that each of us is more a community than an individual. We are, it turns out, in a much more profound way than we ever realized, truly complex systems.

As discussed in Science magazine's "Insights of the Decade" special issue published last month, nine of every ten cells in your body are microbes. Only one of every ten cells that make up the "human" body are  actually human. Some might call this symbiosis, but to me it seems that we're more like little walking eco-systems, carrying around with us a whole host of living things that, apparently, keep us alive and healthy.

Although I find these results inherently fascinating from a complex systems point of view, I have a more personal reason for closely following these developments. As a person who suffers from an autoimmune disorder (specifically, collagenous colitis), I have been particularly intrigued by recent results that seem to indicate that autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and type 1 diabetes, may be due to an imbalance in the population of microbes that live in our bodies.

Many of the microbes in our body colonize various body cavities, including the mouth, the bronchial tubes, the vagina and the intestines, although we also harbor many species on our skin. It is becoming increasingly obvious that these microbes, mostly bacteria, but also fungi, viruses and protozoa, have evolved symbiotically with us and we depend on them for healthy functioning, as they depend on us.

The use of "probiotics," or "good bacteria" in guarding health used to be the province of only alternative health practitioners, but nowadays many of those in conventional medicine encourage the use of probiotic supplements, especially when taking antibiotics. While I think this is a good approach, we know so little about which mix of bacteria are healthy that it's hard to know exactly which probiotics will help.

According to a review published in late December, more than 1000 different bacterial species have been found to be living symbiotically with humans, but each individual person harbors about 160 different species, so my ideal mix of beneficial bacteria may not be the same as yours.

One reason for this amazing diversity might be the recent observation that parts of the human immune system require the presence of specific microbes for both their proper development and function. Certain microbial species apparently help turn on or turn off genetic switches within the human immune system, and each of us has a unique set of switches.

Regulatory T cells dampen inflammation after microbial infection and these are switched on in accordance with genetically-determined factors. A microbe that lives in our gut, Bacteroides fragilis, is now known to produce a polysaccharide molecule that suppresses inflammation. Furthermore, some data from germ-deficient mice imply that the presence of this microbe is actually required for the development of healthy regulatory T cell function. Without this bacterium, it is suggested, we would not be able to mount a defense against other microbial invaders.

Similarly intriguing results exist for the influence of microbes on the down-regulation of inflammation. Since a healthy immune response requires a balance between pro- and anti-inflammatory reactions, an intriguing new possibility that has just emerged is that autoimmune disorders might be the result of what we could call "dysbiosis," or the dysfunction of the microbial colony that lives within us.

A large-scale project to map what is now being called the "human microbiome," or catalog of microbes that make up the colony within our bodies, has been launched by the National Human Genome Research Institute in Bethesda, MD and some of their recent results are described here. I'm going to be carefully watching the results that come out of this effort to better characterize our complex microbial selves. Stay tuned!


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