Gut doctor Rob Knight
Gut doctor
Kiwi expat scientist Rob Knight, cofounder of the American Gut project, is in a car shuttling between Newcastle and Sydney.
The 41-year-old is the big cheese these days. A stack of awards. Director of his own laboratory, the Center for Microbiome Innovation based at the University of California San Diego.
Knight is even professor in a couple of subjects – paediatrics and computer engineering – that he never officially studied but has picked up along the way.
Chatting on his mobile as he is being chauffeured between talks – a rare gap in his busy schedule – Knight laughs off the accolades. Having his own Knight Lab is not quite as grand as it sounds, he protests. It is the US. Every professor with a grad student gets their name above the door as some kind of institute. ‘‘It’s just a cultural thing.’’
However, he does genuinely enjoy a multimillion-dollar research budget, a veritable army of post-docs and research assistants, and the opportunity to drive a field that has become revolutionary in a few short years. He agrees that if he had stayed in New Zealand, getting a university chair might have been literally just that. ‘‘You’d have a nice office . . . with a chair.’’
So the microbiome. You have probably heard by now about that next step in the human genome story – the bacteria, fungi and other microbes which colonise every nook and cranny of our bodies.
There has just been a three-part TV3 documentary, The Good Sh*t, on it. Knight made an obligatory fleeting appearance as an expert.
The series covers an attempt by Auckland University’s Liggins Institute to cure obesity using faecal transplants – shit pills, not to mince words. The theory is that our gut microbiome, the 1.8kg load of mostly good bugs which line our eight metres of internal tubing, is amazingly connected to our state of health, and even state of mind.
A compromised gut ecology – due to a bad diet, the wrong colonising species, the blitzing after-effects of antibiotics – is now being implicated in every kind of ailment from obesity, diabetes, heart disease, arthritis and cancer, right out to depression and autism.
It shouldn’t be such a surprise. School biology teaches us how cockroaches and cows depend on symbiotic bacteria to digest their food.
It turns out we also need a healthy diversity of microbes to do jobs like breaking down fibre or synthesising vitamins. We have evolved to work together as a system.
The Auckland trial was an attempt to recolonise the intestines of a trepidatious group of overweight teen subjects with the right stuff. They had to swallow pureed, double-encapsulated poo from fit and skinny donors to see if it would nudge their metabolisms into a better state.
As viewers saw, the results were mixed. But it is early days. No-one really doubts the microbiome is medical science’s next big thing.
Knight fizzes with the findings continuing to pour out. An Arizona faecal transplant effort is now getting promising outcomes with autism, he says.
In a cancer study, researchers have found that tumours have their own characteristic supporting microbial communities. ‘‘If you treat the tumour with antibiotics first, it kills the bacteria and the anti-cancer drugs can work a lot better on that tumour.’’ Another possibly ground-breaking insight.
He says the implications seem pretty well unlimited. Essentially science has stumbled on to a whole other organ that we didn’t know the human body had.
Knight has found himself at the centre of this particular research breakthrough largely because he has been helping pioneer the technology used to ‘‘bar code’’ the bugs.
First, gene studies led to a convenient tag – a non-coding RNA sequence – that could be used to position every microbe species on its evolutionary tree. Then came the lab tools and visualising software, like UniFrac and the QIIME pipeline, which could provide an instant snapshot of the entire microbial population found on any quick swab.
He says falling cost made the real difference. It might have cost $100 million just to analyse a single person’s microbiome at the start. Now it is about $100 a pop, and heading towards a few cents.
When Knight first took off for America, he admits he had quite a different PhD project in mind. He grew up in Dunedin, his father and mother both being psychological researchers at Otago University’s school of medicine.
He says he had the usual boyhood interest in nature – ‘‘Shells on the beach, rocks on the hills, frogs and animals out in the bush.’’
After Otago Boys’ High, he made the slight mistake of beginning a chemical engineering course at Otago University. ‘‘I didn’t really know what chemical engineering was. I thought it’d be about making interesting new molecules. But it was about optimising industrial processes so you could eke out an extra 1 per cent efficiency, or whatever.’’
However, in school, Knight had already struck on a possible research project – the hunt for a knock-out gene that would make possums infertile. A predator-control technique called gene drive. So while still an undergrad, he got a government grant and then a place at Princeton University to do the research as his PhD.
Knight says, luckily for him, as soon as he arrived, he found another lab had beaten him to it. It had tested the gene he had in mind, showing it couldn’t in fact work. ‘‘That meant I didn’t end up spending the next 15 years tracking down the wrong gene.’’
He switched to another Princeton team that was studying the origins of the genetic code – the beginnings of life on Earth. A sideways step into the real big time.
This got him in on the ground floor with the gene sequencing techniques being used to identify bacteria and so the start of what has become microbiome informatics.
The results were immediately astounding. It turns out we support such a density of microscopic life that – in terms of DNA counts at least – we are actually 99 per cent microbial.
Knight says we are also surprisingly individual in the exact mix of species we each carry. Two humans will share 99.99 per cent of their genes, yet only have 10 per cent of their microbes. And even across our own bodies, every part is a different ecosystem. Bacteria are both incredibly tiny and incredibly specific about their nutrient needs. From their point of view, your armpit and forehead might as well be environments as unlike as rain forest and tundra.
He says one seemingly mad idea was that even your left and right hand might be different enough in what you do with them to provide different microbial environments.
So swab a computer keyboard and there ought to be a sharp dividing line between the species found on the G and H keys. ‘‘That’s been confirmed by studies now.’’
It is the gut microbiome which has been grabbing the headlines, he says. That is largely because gastroenterologists pushed the early research, and then the many spectacular health connections began to leap out. ‘‘But the oral microbiome, the skin microbiome, the vaginal microbiome, are all going to be really important areas of research.’’
Good bacteria act like a protective film to our bodies. And so far we only have a glimmer about the possible interactions. With the vagina, for instance, there are Lactobacillus species that do the job of keeping it acid. There are iron-metabolising Deferribacter species that thrive during menstruation.
The gut research has been throwing up all sorts of red flags for things like artificial sweeteners, emulsifiers, and the phytoestrogens found in soy products.
Life keeps getting busier for Knight. The latest thing is this American Gut project – an ambitious ‘‘citizen science’’ effort to database the microbial diversity of the human race. Volunteers pay US$99 to receive a swab kit in the mail. After dabbing it on used toilet paper, they post the sample back. Online, they fill out a detailed survey on their mental and physical condition. It is all about looking for patterns.
A report on the first 11,000 participants came out earlier this year.
Where could all this lead? Smart toilets to check your gut daily? A microbiome GPS that can tell where you are on the health map and what to do in terms of your diet, lifestyle and medication?
His career wasn’t planned. ‘‘It’s been serendipitous. It wasn’t Big Science back in 2001 or 2002, although it’s rapidly become that.’’
So these days he is as much a manager of the projects. He wishes he had more time to be writing code, working on the machine learning and analytic software. However, as an expat Kiwi researcher, Knight knows he is still only at the beginnings of what is going to be a heck of a scientific ride.
‘‘If you treat the tumour with antibiotics first, it kills the bacteria and the anticancer drugs can work a lot better on that tumour.’’