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Monday, 25 March 2013

The beast with a billion backs: Part 1

This post is by freelance science writer Gavin Hubbard. Gavin originally trained as a Medical Biochemist at the University of Surrey and spent over 10 years working in biotechnology, immunology and clincal trials. He writes both for industry and for a general audience, with a focus on health, immunology and pathology. He blogs at Sciencehubb.co.uk and can be found on twitter as @GavinHub

We like to think of ourselves in the singular, but the reality is we are a swirling composite of thousands of species, more accurately thought of as an ecosystem than as an individual.

There is the core ‘us’, the cells that contain our DNA. But we are also like the land on which a rich forest might grow, with every niche – every nook, cranny, and crevice – a unique home for some of the trillions of bacteria that call us home. Together they are our ‘microbiome’.

Puzzle of Vitruvian Man made with bacteria
Our relationship with bacteria is a complex puzzle.
Image Credit: Gavin Hubbard
But before you run off screaming to the shower, with bleach in hand, you should know that this is no bad thing. For example, in return for shelter and a share of the spoils from our meals, some make vitamins, liberate nutrients and energy from food, and protect us from their pathogenic cousins. Millions of years of co-evolution with our microbial horde have forged this relationship, shaping us both in ways whose significance we’re still trying to understand.

This is the first of a couple of posts that hopes to briefly explore some of the unknowns and open questions surrounding the microbiome and its relationship to our health and well being.

It was about 15 or so years ago that interest in the microbiome really started to pick up. Since then, we’ve caught tantalising glimpses of the bigger picture, and managed to fit some of the pieces of this puzzle together; we’ve even managed make use of the microbiome to cure disease, but much remains a mystery, with only hints about where and what to look at.



Fumbling in the dark

One of the biggest problems in unpicking the microbiome’s relationship with health is working out if the changes and differences are a cause, an intermediate step, or a consequence of developing a disease. When the ecological balance starts to shift, for whatever reason, there is a complex set of interactions involving our genes, the food we eat, the microbiome we inherited from our parents, the people we interact with – and their bugs. In short: separating our environment from disease is proving hard.

Crohns disease is a good example; we know a disrupted microbiota is one of its features. But we can’t yet say for sure if this is the cause or the effect. Is this disruption due to a change in physiology creating a new niche, colonised by a new community of bugs? Or does some environmental factor change the function of the microbiome, allowing new communities to grow, ones that wreak havoc, causing Crohns? Correlation is not the same as causation.

It’s in important distinction to make, not only because it changes the kinds of interventions we investigate to help cure or prevent Crohns. If it starts with our own physiology, then we need to investigate treatments targeted at those changes, but if it starts with the microbiome our treatments will be different. Maybe we could reintroduce a ‘healthy’ microbiome, or encourage one to grow back somehow – possibly through diet, but maybe in some other way too.

Phylogenetic tree of life
With so many branches it’s perhaps no surprise that so many other organisms can call us ‘home’.
Image Credit: NASA Astrobiology Institute

To me. To you…

In the past we’ve been well served by the one-pathogen-one-disease model for tracking, monitoring and avoiding infectious diseases. But do beneficial, or harmless, bugs in the microbiome spread like pathogens? If not, how? Surprisingly, we know little about this, and the tools from the pathogen models may be of limited use, since a beneficial microbiome may be thousands of microbes, constantly changing, but around a stable equilibrium.

It will likely need a holistic approach; it’s an epidemiological problem, but we will need the tools and ideas from ecology if we hope to be able to characterise the communities, dynamics and flow of the microbiome's members.

It is important to understand this because of the number of links between the microbiome and a number of diseases like diabetes, inflammatory bowel disease, food allergies, and even obesity. An improved picture of how our communities of microbes – good and bad – come together and move through populations could help us to develop interventions to significantly reduce, or prevent, the numbers of people with these conditions. Or, at the least, find ways to hobble this trend.

The need to understand our microbiomes relation to disease – as well as correlation/causation – is well illustrated by a study of 317 twin pairs in Malawi. In up to 43% of these twin pairs, one twin would show signs of a type of serious malnutrition called Kwashiorkor, despite the other twin being perfectly healthy. While the twins genes may not differ significantly, the genes of their microbes did. Over time the healthy twin developed a diverse set of microbes and their genes while their Kwashiorkor suffering sibling’s microbial gene pool stood still.

Map of London Cholera epidemic, 1854, by John Snow
Epidemiology is the study of the causes, movements and patterns of diseases.
This is a map of Cholera cases from the London epidemic of 1854. Public domain image.

Escape

Once we establish if the microbiome is a cause or consequence (or something in between) and how a ‘bad’ microbiome comes about, we may be able to devise ways to treat or prevent disease that don’t require direct medical intervention, as with something like transplanting a ‘healthy’ microbiome.

Understanding both the flow of microbes and the factors which influence it may also be important for any treatments we produce. For example, if an ‘artificial microbiome’ were developed for a specific disease, we might reasonably expect this ‘artificial microbiome’ – or elements of it – to begin travelling through a population too. How would we evaluate the safety and impact of this? Could we?

We’ve been manipulating our microbial ecosystems for years, both naturally through our immune systems and, perhaps more worryingly, through a weapon of microbial mass destruction: antibiotics. The next post will look at the questions still to be resolved around how our microbiome tolerates these attacks, how do they respond, and how does this affect us?

Read on in The Beast with a Billion Backs, Part 2