Bugs as Drugs – and beyond
You may be familiar with recent studies involving transfer of the gut microbiota (read poop) from lean and obese mice into germ-free mice which resulted in the now not-so-germ-free either remaining lean or becoming obese respectively.
One of the most interesting sessions I attended at June’s BIO 2017 – the world’s largest biotechnology event held in June - was a panel discussion which contemplated this and much more.
Microbiome 2.0: Going Beyond Bugs as Drugs was one of many fascinating sessions on the understanding and treatment of disease, a major theme as the convention canvassed the theme of breakthroughs. Speakers came from J&J (Stephanie Robertson); Leading BioSciences (Tom Hallam) as well as academia (Professor Scott Peterson).
The human microbiome – the collective genomes of the microorganisms (bacteria, fungi, viruses etc. – commonly known as bugs) that hang out on or within the human body – has garnered a lot of attention in recent years. It has been linked to a number of diseases, including cancer, bowel disease and obesity.
It turns out that our bugs have a powerful influence on our overall health and on a range of health conditions, and using bugs as drugs has been one of the main focuses of the microbiome space. However, these colonies are complex, and can change over time (in some cases quite rapidly – one of the comments made in this session is that every time you eat you change your gut microbiota). So, there are a huge number of variables to control and understand before we can reliably manipulate our microbiome to generate better health outcomes.
One example of a new approach is modulating the gut microbiome to improve patients’ responsiveness to a new class of cancer therapies called checkpoint inhibitors. While these new therapies can be extremely effective for some patients, many fail to respond, and there can be significant toxicity issues (i.e. the drugs make patients even sicker). Significant work is now going into trying to identify a microbiome ‘signature’ that will predict how a particular patient might respond. Interestingly, the gut microbiome can also play the villain, converting drugs into molecules that are even more toxic. Getting a better understanding of these interactions will result in better outcomes for patients.
The panel also discussed a new way of thinking about bugs. Traditionally scientists have thought of microorganisms in terms of taxonomies or species, but Scott Peterson suggested it made more sense to understand bugs in terms of their genetic makeup. A typical gene count for a typical microorganism is around 3000-5000. Humans, by comparison have around 19,000-20,000. Our human genomes can vary by about 10 percent, compared with around 70 percent for bacteria. If we treat bugs as bags of genes we can better understand the ways in which these microbes (genes) affect or modulate our immune system and overall health.
And of course, no panel discussion on the human microbiome would be compete without time spent on the so-called gut-brain axis. In case you’ve been living under a rock for the past few years, the gut-brain axis refers to the biochemical and neural signals that travel between the gut and the brain.
I was horrified to discover the details of how this can work. For example, a sugar-loving bacteria can produce enzymes that can travel to the brain and cut out the signals of satiety, meaning you crave more sugar. I was wondering how on earth this might happen (our gut is a fairly hostile environment for proteins), and it turns out that all you need is a “leaky gut”. Basically, these enzymes can leak out from anywhere even slightly damaged in the intestine and be carried in your plasma to your brain – where they can have an influence not always understood.
Making you eat more junk food might be the least of your worries, as new evidence suggests a link to Alzheimer’s as well. Yikes! Correcting the ecology of the microbiome so that bad things don’t happen could have a massive impact on human health and disease.
Given the increasingly vast amount of relevant data we can access and the level of complexity associated with the various microbiome - human interactions, how do we wade through all of this to reliably achieve good health outcomes?
Unsurprisingly the answer to this is Big Data. Integrating DNA sequence data with other sources of data such as RNA and protein sequences, as well as characterising the metabolites present within a microbial community, will give a clearer picture of that community and its influence on health.
I will write more about Big Data and Biotech next time, but for now I will come full circle and leave you with this factoid to consider. According to Prof Scott Peterson, 40 percent of the dry weight of faeces is bacteria – which means that it is full of information. So, the next time someone tells you you’re full of it, you should take it as a compliment!
Contact Kimberlee Jordan on Twitter @kimberlee_j
Callaghan Innovation is a New Zealand government innovation agency that works with Kiwi companies to accelerate commercialisation of their new technology ideas. Our National Technology Networks team supports businesses via our four technology platforms – Advanced Manufacturing, Advanced Materials, Biotechnology and Data & IoT, with the aim of helping companies rapidly connect to new and advanced technologies.