A belated Happy New Year to you, readers of Evolution Medicine! In 2020 I am introducing a new new initiative – the Bad Microbiome Project. Pictured above is a member of the Enterobacteriaceae family – E. coli – a prototypical bad microbe. The bad microbiome project is an exploration of the many ways that your microbiome can kill you – quickly and slowly.  Working in a busy emergency department as I do, I am aware of the omnipresent threat of death. Applying that frame to the microbiome can be a useful exercise.

At its core, bad microbiome is, of course, an evolutionary story. It is a universal evolutionary priority for organisms to stay alive and reproduce. Those priorities often come into conflict in the complex relationship between hosts (like ourselves) and our resident microbes that make a living in communities on our skin, mucous membranes and in the gastrointestinal tract. I hope to show you how conflict drives disease in ways that are unexpected and interesting. We have explored this topic in previous posts, and you can expect much more in the weeks to come.

In 2012 I did an informal survey of attendees at a Keystone conference on the microbiome. I asked whether a germ free animal would be expected to have a longer or a shorter life. Most respondents thought lifespan would be shortened. Of course that would be true if a germ free animal is set loose in a world full of microbes, such as ours. But if the host could kept in a microbe free environment, most studies suggest that germ free animals live longer. Germ free animals also grow faster. Being germ free also protects from mortality when animals are subjected to experimental sepsis, hemorrhage, or trauma:

The lesson from these germ-free experiments is that a microbiome is a two-edged sword. We know that endogenous microbes can be protective, e.g. from Clostridiales difficile infection. But the microbiome can exact a substantial cost to the host, including the risk of invasive infection. Even when microbiomes do not kill us directly, hosts must expend energy to manage their microbiomes. The threat of microbiomes gone bad forces hosts to take risks and engage in costly tradeoffs. The point here is not to argue that all microbiomes are bad. Instead, the ever present potential for microbiomes to go bad explains why our bodies appear to self destruct in a variety of chronic and acute diseases.

The microbiome can also predict whether we live or die. In an editorial I wrote a number of years ago entitled “Dangerous disappearing act”, I highlighted work by Hayakawa and colleagues that describes how the microbiome of critically ill patients can predict death. More recent work from Finland suggests that life or death can be predicted by the microbiome in the general population. Salosensaari and colleagues uncovered a relationship between certain microbiome characteristics in the human gut microbiome that predicted mortality during a 15-year follow-up of eastern and western populations of Finns. Interestingly the signature that was most strongly related to mortality was related to the Enterobacteriaceae family – the one that includes E. coli. It is handy that we can point to one group, the E. coli group, that is related to bad outcomes. Of course Enterobacteriaceae is not alone in this. We will spend the next few entries exploring how microbiomes go bad, and impact the odds of survival of their hosts.

Read the Salosensaari preprint here:  https://doi.org/10.1101/2019.12.30.19015842

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine