The microbiome, the gift that keeps on giving…

In recent years, stories about the microbiome have become pervasive. The microbiome is defined as all of the microorganisms in any environment, however many people usually think of a microbiome as all of the microorganisms that share the human body – be they bacteria, archaea, viruses, fungi and protists. Studies have linked the microbiome to a range of conditions from autism to obesity and diabetes and beyond. Seldom does a week go by without a story in the news of a new scientific paper reporting how the microbiome is the underlying cause of a particular condition. There is a need to have a healthy degree of scepticism over the plethora of microbiome studies out there and a couple of years back, Prof Bill Hanage of Harvard Medical School wrote an excellent Comment in the journal Nature related to this. Moreover, the explosion of interesting microbiome studies in the literature has certainly encouraged a resurgence of interest in microbial ecology, a discipline that was seen as stuffy and outdated for many years until the microbiome came along. However, we need to remember that every centimetre of planet Earth is a microbial ecosystem be it a crumb of soil, the Sahara Desert or the human skin or gut – everywhere has a microbial ecology!

Despite the hype associated with some of the microbiome research, there are some really excellent and fascinating studies being conducted. Recently, a group of scientists from the University of Tubingen in Germany published a study in the journal Nature that describes the discovery of a type of bacterium, found within the human nose microbiome, that is able to produce a new type of antibiotic that can control the growth of pathogenic bacteria, such as the tabloid favourite, Methicilin Resistant Staphylococcus aureus (MRSA).

There is an urgent need to develop novel antibiotics due to the emergence of antibiotic resistant infections in the clinic. In recent years this problem has focussed the mind of policy makers, scientists and the public, and recently in the UK resulted in the publication of the O’Neill ‘Review on Antimicrobial Resistance’.

Much of the press coverage of the Tubingen group’s work (Guardian; Independent; BBC; Telegraph; Huffington Post) focuses on how surprising it is that organisms within our own microbiome are producing chemical compounds (often referred to by chemists as ‘small molecules’) that kill other bacteria. However, we have known that there are complex chemical interactions occurring between all organisms wherever they live, be it soil, water or within the human microbiome. Indeed, this is not the first report of this nature, with a group from the USA demonstrating a couple of years back that the human microbiome is a hot-bed of small molecule production, with some molecules produced representative of well-known classes of antibiotics that are used in the clinic.

Where this new study is interesting and differs from previous studies is that the authors have been able to demonstrate that there is a new chemical class of molecule being made (the authors called this Lugdunin), that could go on to be useful in human medicine and it was previously unknown. Secondly, the authors were able to show that when the lugdunin producing bacterium, Staphylococcus lugdunensis, was found in patients, those patients had a significantly reduced amount of MRSA in their nose. This suggests that when S. lugdunensis is present, it is much more difficult for MRSA to get a foothold within a patient’s nose and potentially then go on to cause infections. Where this becomes very important is that the majority of serious and life-threatening bacterial infections are the result of opportunistic (and potentially drug resistant) pathogens that already live on or in a patient without causing disease. Only when the patient undergoes surgery or other clinical interventions do these pathogens become a problem, causing infections. Therefore, if we can artificially colonise patients with organisms that reduce the number of potential pathogens carried, then perhaps we can reduce the number of life threatening infections.

One caveat to this whole story is that while S. lugdunesis was shown to interfere with MRSA carriage in patients, it has also been associated with human soft tissue infections, so this is unlikely to be the end of the story. What it does represent is that in a complex ecosystem, such as the human microbiome, there are interactions between species of bacteria occurring all the time, and that up until now we have had very little insight into these. So, just as in macro-ecosystems (the kinds of ecosystems we are familiar with such as forests and grasslands), the introduction of species can have unintended consequences (think Cane Toads in Australia) so it is unlikely that we will be introducing antibiotic producing strains into humans just yet! However, the opportunity to discover potential new drug molecules from unusual and unfamiliar hunting grounds may just be a profitable route to combating antibiotic resistant infections.

Zipperer A. et al. (2016). Human commensals producing a novel antibiotic impair pathogen colonization. Nature. DOI: 10.1038/nature18634