Sequencing the Microbiome

New technologies that can rapidly read the DNA sequences of bacteria can be used to study how different bugs move between us...
21 October 2013

Interview with 

Jack Gilbert, Argonne National Laboratory, Chicago


New technologies that can rapidly read the DNA sequences of bacteria can be used to study the way individual bugs move about, how they affect our health and how we can minimise the risks of them becoming resistant to antibiotics. Chris Smith spoke with Jack Gilbert, from Argonne National DNA HelixLaboratory in Chicago to discover how...

Jack -   You're shedding about 15 million bacterial cells into the immediate environment around you every minute.  Those 15 million cells comprise mostly of bacteria associated with skin, but they also come from your nose and your mouth, and interestingly, even from your gastrointestinal system via your trousers and on to these seats you're sitting on.  So, you leave a signature wherever you go.  And those bacteria land on the surface, most of them die, but some of them go dormant or they proliferate, then they can be transmitted from you to another person.

Chris -   Which means if we were in a hospital and another person comes into that part of the hospital where someone with a certain type of bacteria has been, there is, therefore, the prospect for them to pick up those bugs.

Jack -   Precisely and we believe this is the main element of transmission.  There's a hypothesis which stipulates that it's really just people touching each other.  So, when you go and shake hands or you hug, or the doctor comes and talks to you and pats you on the shoulder, that's where that transmission comes from.  There's an element which believes it is just in the air - i.e. the bacteria living on little bio-aerosols, these little particles in the air and you inhale them and that's where you get the infection from.  And there's groups that believe that the bacteria live on surfaces.  You go along and touch that surface after someone else has touched it and you're going to catch that bacterium.  But there are literally tens of thousands or hundreds of thousands of bacterial species living alongside the bad ones that make you sick.  We don't understand what role they play in promoting or suppressing the transmission of those pathogens.

Chris -   So, there are good guys, there are bad guys.  The good guys might stop you catching the bad guys, then they also do other things to your body to keep you healthy.  What don't we know fundamentally and how can we find out the answers to those questions?

Jack -   Only in the last, say, 10 years have we had technology which enables us to rapidly and adequately describe these environments and these communities.  So, we're just touching the surface.  In a human body, there are 100 billion bacterial cells and we have spent the last 5 years cataloguing those extensively.  But without much benefits, we're still making literally making a catalogue, a shopping list of the bacteria that live within us and what they do.  We are finding extraordinary things.  They influence our behaviour.  They influence our mood.  They can determine whether you are depressed or anxious.  They also influence our disease state, i.e. if you have a healthy bacterial community in your intestine, in your mouth then that can prevent you from getting a pathogenic infection.  They have to increase or decrease your metabolic clock inside your body.  So jetlag, we can potentially cure by putting the right types of bacteria back inside your gut.

Chris -   How can we use this understanding to make sure we either don't get antimicrobial resistance or to mitigate what we already have got?

Jack -   That's a very complicated question and that's exactly what we're here today to try and uncover.  How do we design the best experiments possible so we can determine exactly why certain bacterial communities may affect that process.  One of the fundamental problems that we have is that we don't understand which bacteria are out there and how they interact together.  So, by defining those links, saying how bacteria talk to each other daily, finding out how they communicate and how they respond to that communication could change the way we think about disease infection.  Especially antimicrobial resistance because it's when those bacteria talk to each other that they transmit that resistance between each other.  So, we need to understand that fundamentally.  We believe that the hospital environment "may" be - I stress "may" - may be a reservoir of antimicrobial resistance.

Chris -   So, how can we answer those sorts of questions?  What are we armed with in terms of the tools to do this research now that we didn't have in the last 10 years?

Jack -   We've fundamentally increased our ability to sequence the genomes of these organisms.  Much the same as the Human Genome Project, we can sequence a bacterial genome for $300 now and that data stream is helping us to ask - where before, we would've analysed 20 or 30 patients, now, we can analyse 20 or 30,000 patients.  That ability changes our capacity to do statistical analysis.  As any scientist will tell you, if the statistics don't hold up, it's not true.  So, we need that power.  We need that number of observations to really get at the statistical integrity.

Chris -   So, you can use DNA technology to probe what are these bacteria which I presume is going to be good news, because not all bacteria grow where previously we tried to grow things in dishes.  We would've missed some, so that may be a factor too.

Jack -   So, this is exactly the idea that some organisms grow really well in the lab and that's what we've been looking at.  But there are circumstantial evidence which suggests that a lot of the diseases we encounter, we don't know what bacteria or what virus causes that disease.  So, these kinds of analyses that look at bacteria in situ with sequencing technologies and we can identify bacteria which are always present when that person has that illness, always present when multiple people have that illness.  It helps us to identify new diseases.

Chris -   Can it also help us to identify who may be at risk of a disease?

Jack -   The concept of this is, that the bacterial community in your body undergo what we would call dysbiosis.  They're no longer in symbiotic union with us.  When that symbiotic relationship breaks down, we are open to all kinds of mischief.  Different pathogens can infect us.  Our metabolic states in our guts can change.  Our liver condition can change.  That has serious implications for our health and well-being in a hospital.

Chris -   Jack Gilbert from Argonne National Laboratory in Chicago and thank you also to the foreign office's, Jack Westwood.  He is based at Science and Innovation Network in Chicago.  He invited us to that meeting.


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