I’ve been asked to tell some disgusting stories from the trenches – almost literally, our lab is in a very neglected basement – of microbiological research. I’m not emotionally prepared to talk about the soggy, dead rat that I pulled out of our broken down and moldy -80 freezer, so instead I’m going to start a series of articles on the microbiome, which is what we study. Microbiome research is currently in vogue in scientific circles, but despite the hype has some fascinating implications to medicine, ecology, and even how we define what makes up a human.
We like to think that the only barrier between the world outside and inside our bodies is our skin, but in fact, the interface between our bodies and the world is mediated by bacteria. Trillions of them. Bacteria outnumber our own cells by a factor of ten. Your gut, eyes, respiratory tract, ears and vagina are covered with a mucosal layer that is inhabited by bacteria. What’s more interesting is that these aren’t just any bacteria that you would find in the environment, but species that are exquisitely evolved for life on or in the human body. Bacteria begin their colonization of our bodies the moment we are born, are nurtured by our mother’s milk, and without their presence, our immune and digestive systems would not develop correctly. In fact, the bacteria within our guts contribute a great deal to our digestion, and can be considered a distinct organ in their own right (O’Hara, A.M., Shanahan, F. 2006, EMBO Reports 7(7):688)
Despite the importance of all these bacteria, we know almost nothing about them. Very few can be cultured in the laboratory, and until recently microbiology was only concerned about the bacteria that cause problems. It could be argued that our current ultra-hygienic lifestyle and over-use of antibiotics stems from the bias that drove years of microbiological research: bacteria are bad for you. In fact, your associated bacteria are overwhelmingly benign, and some protect you, improve your digestion, and can even improve your mood.
I am involved in research on bacteria that colonize the upper airways of children. I’ve compared the bacteria that live in adults to those that live in children and the communities are different in a number of ways, but most strikingly, children can harbour one to two orders of magnitude more bacteria in their upper respiratory tract than adults. The type of bacteria they have may differ but they are definitely more likely to surprise you with the odd enteric bacteria than adult samples. In other words, I can prove that children pick their bums and noses interchangeably. We are interested in developing therapeutics against pathogenic bacteria that can cause ear infections, pneumonia, and meningitis in children. However, what is fascinating is that respiratory pathogens can hang out in the respiratory mucosa for years and not cause any problems. In fact, the amongst healthy children, 30-40% can be carrying the causative organism for a nasty pneumonia, Streptococcus pneumoniae (serotypes covered by the PCV-7 vaccine in the Netherlands, Spijkerman, J., et al. 2011. Emerging Infectious Diseases, 17), 22-50% of teenagers can be carrying the causative organism for bacterial meningitis, Neisseria meningitidis (among university students in the UK, Ala’Aldeen, D.A.A. et al. 2011. Emerging Infectious Diseases, 17), and almost all children 1 year – 18 months seem to carry the bacteria that can cause ear infections, Moraxella catarrhalis, in my study (unpublished data). Clearly, not all these children are getting sick from the bacteria they are carrying, but what can trigger a potentially deadly infection is not well known. A viral infection, such as a cold or flu, often precedes an infection, but why some kids get sicker and others get well is very unclear.
The question may be addressed by not only identifying the bacteria in these samples but determining what they can do. What I am looking at right now is how many of these bacteria exhibit traits that we normally associate with pathogenesis. We’re finding that the presence of many of these phenotypes within the same species can be quite variable (Grinwis M.E. et al. 2010. Journal of Clinical Microbiology 48(2): 395). Complicating matters is the predilection for respiratory bacteria to share their genes. Many bacteria that inhabit the respiratory tract are capable of taking up DNA they find in their environment, and either eating it, or incorporating it into their own chromosome. This is called natural transformation, and greatly complicates our ability to put bacteria into neat categories. In fact, natural transformation has been shown to be extremely prevalent amongst this group of bacteria, far more so than bacteria from other body sites, or from the environment (Shapiro, B.J., and Alm, E. 2011. PLoS Genetics, in press). The ability of bacteria to share their genes also means that they are capable of rapid evolution, which makes it difficult to treat them. Antibiotic resistance has been increasing amongst many bacteria, and even those cellular characteristics targeted by vaccines have been shown to be switched out by pathogens, mostly due to natural transformation (Croucher, N. J., et al. 2011. Science, 331: 430).
This makes the question that I deal with suddenly more interesting to me, because now a question of human health is also a question of bacterial evolution and ecology. I wonder whether the species that inhabit the upper airways of healthy kids are really neatly defined by their species identification. When we identify a bird in the wild, it has many characteristics that make it, say, a robin. It has a red breast, shows up in my neighbourhood in the spring, and sings beautiful songs from the peaks of roofs to attract a mate. It eats worms and lays blue eggs. It’s a robin for many reasons. However, quite often bacteria are identified on the basis of the DNA sequence of their ribosomal 16s gene. Given the prevalence of horizontal gene transfer, we can’t be certain that the each individual within a group that have the same 16s sequence has the same suite of genes. This makes understanding the ecology and evolution of bacterial communities in our various microbiomes so much more interesting, and so very important for understanding our health.
Over the next few weeks I’ll talk about fascinating new research into how the microbiome affects our immune system, our weight, and even our moods. I’ll talk some more about the respiratory microbiome of small children, or as I like to call them, walking cesspools. I hope that in the end you’ll appreciate the trillions of beings that are with you for the ride.
