Feeling lonely? No need: At any given time, there are literally trillions of microorganisms crawling on or in you. For instance, a 200-pound adult carries around two to six pounds of bacteria wherever he goes. Although that might sound disturbing at first, this ‚cohabitation‘ is essential for human health: these bacteria produce certain vitamins, help us break down nutrients or teach our immune system how to recognise dangerous invaders.
The entirety of all of these microbes living in or on us is called the ‘microbiome’. Nobel Laureate Joshua Lederberg first coined the term in 2001 in reference to the human genome project, as the genes of these microorganisms outnumber our own genes by a factor of 150. Lederberg originally used the term to describe an “ecological system of commensal, symbiotic, and perhaps pathogenic microorganisms that reside in the human body”. Such a system, however, is not exclusive to humans, and it turns out we all harbour more than one “system of microorganisms”. Thus, today the term microbiome refers to a “collection of genomes of microorganisms living in a specific niche”, while the group of microbes themselves is referred to as ‘microbiota’. In other words, we are host to several microbiomes where the microbiota are specialised for a certain environment, for instance in our mouths, or noses, pharyngeal systems, our intestines, or on our skin and many more niches across our bodies.
When Lederberg received the Nobel Prize in Physiology or Medicine in 1958 together with George Wells Beadle and Edward Lawrie Tatum, the concept of a microbiome didn’t exist yet. Instead, Beadly and Tatum shared half of the prize for their discovery “that genes act by regulating definite chemical events“ while Lederberg received the other half „for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria.“ We now know that it is precisely this distinctive genetic make-up of some bacteria that allows us to break down our food and provides us with certain vitamins.
Since then we have learned a lot more about the function of bacteria and certain microbiomes: they have been linked to diseases ranging from mental health disorders to diabetes, inflammatory bowel disease, cancer and even AIDS. By the same token, the microbiome also seems to be affected by a variety of factors – ranging from lifestyle choices such as diet, exercise or stress levels to our own genetic make-up and the medication we take. Moreover, researchers could show that babies who are born by C-section rather than vaginal lack certain microbiota. Although the specific health effects are not yet clear, the lack of these microbes could be linked to a higher susceptibility to develop allergies later in life.
The microbiome that has probably been studied the most so far is the ‘gut microbiome’. It’s location giving way to its most prevalent involvement: digestion. However, the gut microbiome not only helps to break down food, it can even affect our appetite: microbiota used to digest highly processed food will most likely induce a craving for exactly those kinds of food products – a vicious cycle that can be hard to break. Additionally, treatment with antibiotics has been shown to disrupt the function of the gut microbiome. In extreme cases these malfunctions can only be restored by fecal transplants.
However, it seems the gut microbiome is capable of much more: a recent Nature paper pointed out that two thirds of the tested drugs (medications) were metabolized and significantly changed in their function by the gut microbiota. So far it has been assumed that drugs are mostly metabolised by the liver and that the differences in patient responses are rooted in the individual genetic differences of the patients. However, as Zimmermann and colleagues now found out in their paper, specific microbial gene products metabolise the drugs – precisely due to the distinctive genetic material and properties that Lederberg received the Nobel Prize for.
Particularly in the context of personalised medicine this is a very important finding: in order to establish individually tailored, personal treatment plans for patients, their gut microbiota need to be analysed as well. This is especially significant, as more and more treatments are administered orally, rather than by injection, in which case the gut microbiota could be circumvented. The pharmaceutical industry has already identified these microbes as a new potential drug target and many companies are well on their way to develop targeted small-molecule approaches.
One could get the impression that the microbiome is the latest fad not only in research but also in newspaper articles or even on TV: for instance, there are numerous yoghurts and pills advertised that aim to enhance our gut microbiota and many crèmes that supposedly improve the look and durability of our skin by acting on the skin microbiota. Any microbiome, it seems, is a good thing that is worth paying for in order to enhance its function.
Or is it? New research also points to microbiomes as the root of or at least involved in the development of many diseases: for example, first connections have been drawn between changes in the gut microbiome and fibromyalgia, as well as amyotrophic lateral sclerosis (ALS), Alzheimer’s or Parkinson’s disease.
So what is the answer? Do we get sick because of malfunctioning microbiomes or are our microbiomes malfunctioning because we are sick? Does the microbiome offer a well of new therapy targets or is it the root of all-evil?
As with so many things, the truth lies somewhere in-between in an equilibrium: a healthy lifestyle contributes to healthy microbiomes and vice versa. Everything we put into our body not only affects our cells but also the microbiota – and is in turn affected by these microbes. Moreover, just as everyone’s genetics are unique, so are everyone’s microbiomes and the interplay between the two. We couldn’t survive without either of them, but they can also ‚mutate‘ and become pathological. We live in symbiosis; up to three percent of us are made up of microbes. We are never alone, and it takes a well-balanced village of microbes to keep us healthy.