Forward speaks to Dr James Kinross about the latest themes in research, the insights from his academic career and his ‘bonkers’ secret to a healthy gut.
Forward: features are independent pieces written for Mewburn Ellis discussing and celebrating the best of innovation and exploration from the scientific and entrepreneurial worlds.
Dr James Kinross shot to fame with his book, Dark Matter, which explains the mysteries of the microbiome. He tells Mewburn Ellis about the latest themes in research, the insights from his academic career and his ‘bonkers’ secret to a healthy gut.
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The microbiome is a red-hot topic at the moment, with the press awash with the latest research. Health-conscious consumers are buying fibre supplements, probiotics and prebiotics to boost gut flora. The commercial side is blossoming, producing pioneering enterprises such as breast milk microbiome startup BoobyBiome, soil microbiome company FA Bio and the Asian microbiome library.
Dr James Kinross is in part responsible for the surge in interest. His book, Dark Matter: The New Science of the Microbiome, appeared two years ago to rave reviews – ‘important and devastating’ said The Times – giving the general public a single-volume guide to the latest research in the field.
At a stroke, Kinross became the media’s favourite spokesperson on the microbiome.
‘The book changed my life in lots of unexpected ways,’ he says. ‘Interesting people call me up and ask me to collaborate. I’ve been involved in projects that I would otherwise never have been able to do.’ He recently helped the BBC’s health editor boost his gut health and did a two-part Q&A with Guardian readers.
His appeal lies in fusing three roles: academic, entrepreneur and writer. Kinross is a consultant surgeon at Imperial College London specialising in robotic and minimally invasive surgery for colorectal cancer, and a visiting professor at the Royal College of Surgeons of Ireland. He’s an inventor, currently building an automated endoscope. And he’s a ‘microbiome evangelist’, staying in touch with research worldwide. For example, he works with the African Microbiome Institute to analyse how diet may cause diseases common in the west such as cancer.
‘My gift, if you like, is translational,’ says Kinross. ‘There are a lot of brilliant scientists doing first-class research and I’m trying to make it more accessible.’ As the field diversifies, he’s a guide with a unique global overview.
What’s new in microbiome research?
So what trends is he seeing across the research? ‘It moves so quickly,’ says Kinross. ‘There’s a lot of focus on causation. We’re transitioning out of two decades of association science, where we are trying to find correlations between microbes and disease states, and into the mechanisms. The how and the why.’
Kinross has cited, for example, a study of 2,124 people showing that individuals suffering from depression have distinct gut bacteria. Levels of Coprococcus and Dialister spp. bacteria, which produce the pleasure chemical dopamine, are lower in people with depression. Higher levels of bacteria such as as Faecalibacterium are associated with better moods, although he says that ‘for now it’s not clear which comes first, the gut or the brain’. The goal is to go beyond correlation and discover what’s truly happening – not easy in an ecosystem of trillions of microbes, including 2,000 species of bacteria and 140,000 or more species of virus, plus archaea, helminths, protozoa and fungi.
‘We’re trying to map and define the virome and the phagome, and then attempting to understand the interaction between members of different kingdoms and how they work together,’ he explains. ‘There have been huge advances in our understanding of some gut-brain interactions and how bacteria influence brain development. We’re beginning to tease out some of these pathways.’
Once that’s done, targeted intervention is possible. Kinross says: ‘It’s interesting to know all this stuff, but how do we make it useful and create a therapy? This is at an early stage. We’ve seen a couple of drug trials not deliver. That teaches us that there’s a lot of complexity in the microbiome and we’ve got a lot further to go before we can leverage it.’
New methods are changing the way research is conducted. ‘Two things are transformative,’ says Kinross. ‘The first is deep learning in AI, which is made for microbiome science. Omics integration is how we map what’s happening on a gene to a protein and metabolite. It’s super, super complicated, but AI is the key to unlocking that. We’re seeing exciting science happen.’
The second breakthrough is new models for studying mechanisms: ‘Animal models don’t translate well to human disease. You can’t just recapitulate a humanised microbiome in an animal. What we’re seeing now is very sophisticated organ-on-a-chip, which replicate all the cellular structures. For me, it’s the gut. It’s possible to grow very specific communities of microbes on those chip systems and examine, in a controlled way, how bugs regulate the enteric nervous system, or how they break drugs down. Progress is at lightning speed.’
Combined with other research methods, such as the mass sequencing of microbes, the idea of finding patterns of causation starts to look more plausible.
How to improve your gut microbiome
Another theme in Kinross’ writing is the worsening condition of the microbiome. Gen Z are four times more at risk of bowel cancer than Baby Boomers. Alzheimer’s is increasing. Obesity has been trending upwards since the 1970s. He links these to the collapse of microbial ecosystems. The word he uses is ‘crisis’.
A big part of Kinross’ appeal in the popular media is the sense he can help us with our own health travails. So what’s he telling people right now?
If you want healthy guts, start young, he says. ‘We think the mis-assembly of the microbiome in early life is very important. My research started in bowel cancer, and I’ve gone back and back in time, down to infancy. If you don’t begin life well, you don’t have an immune system to deal with the modern world. We need good longitudinal cohorts of patients to unpick this, but gut-on-a-chip systems are allowing us to speed up the analysis to get the mechanisms.’
Babies benefit from vaginal birth microbiome transfer, and imbibe their first flush of bacteria, viruses and archaea from breast milk. A child born by caesarean section and given antibiotics in the first 12 months of life has three times the risk of developing asthma. Diabetes, sepsis, and childhood leukaemia may have links to dysbiotic infant microbiome.
Avoiding antibiotics, unless necessary, is a given. ‘In the last 70 years we’ve had an onslaught against all microbial life on the planet. Antibiotics are in livestock, in our water, in our soil. Absolutely everywhere. I tell people we’re experiencing an internal climate crisis. A massive loss of biodiversity. I don’t want to be negative, to frighten people. I want a call to action.’
He urges people to take control of their health. Decline antibiotics for mild ailments and choose foods known to be good for the gut. ‘As an individual you have agency over these things.’
His most passionate message is unexpected, almost spiritual. ‘We talk about the gut microbiome, the soil microbiome, the oceanic microbiome, and others. All these are connected. You may or may not be familiar with the One Health philosophy. This is the idea that our health is defined by interconnectedness. We are connected to the food we eat, the way it is grown. All the microbiomes exist in one big cycle.’
Thus, interventions must go way beyond microtargeted inventions.
‘It’s about reconnecting with nature,’ he says. ‘I’ve spent the morning down at Phoenix Farms, which is a charity by Imperial College healthcare. I want my patients getting their hands dirty in a positive, constructive way. Socialising more. It’s changed the way I live, reconnecting to the nature microbiome.’
He says: ‘I think anyone listening to this interview must think I’m completely bonkers.’ Not at all. The growing volume of research connecting stress, social life, soil microbes and health emphatically supports this view.
Faecal microbiota transplants
For extreme dysfunction there is faecal microbiota transplant (FMT). The scientific merits of transferring the faecal microbiota of a healthy person to someone with a depleted microbiome following antibiotics, or to treat ulcerative colitis, irritable bowel syndrome or other conditions, is well documented, but FMT is still a rare therapy. Why is it so under-used?
‘FMT in the UK is licensed for one use, which is Clostridioides difficile infection,’ explains Kinross. ‘In the US, the FDA has licensed commercial FMT products for C. diff. We’re now hopeful that more live biotherapeutic products will come to market. But the regulators are being cautious because the evidence base is still emerging. In the UK, if we want to treat other cases, we need to do a compassionate-use case application. We’re hopeful that this is going to change in time.’
He’s careful not to blame the regulator for the hold-up. ‘That would be unfair. They’ve exercised due caution. The fear is that there are a lot of unknowns. If we change someone’s microbiology, permanently, there may be consequences. That said, FMT is remarkably safe. We use it in really, really sick people with no immune systems, and it’s extremely well tolerated. I think in the field we are hoping the regulators are going to be a little more progressive and allow us to go further than they have historically.’
In theory, FMT could treat gastrointestinal diseases such as ulcerative colitis and Crohn’s, metabolic disorders including obesity and type 2 diabetes, and even asthma and multiple sclerosis. It’s easy to see why Kinross is so enthusiastic about the potential of FMT in healthcare.
Self-driving robots
Kinross is pushing boundaries in his day job too. He’s a pioneer in robotic surgery. ‘We’re funded by the Engineering and Physical Sciences Research Council (EPSRC) to develop a self-navigating, self-driving endoscope,’ he says. ‘Part of the challenge is mechanical engineering, how to propel the endoscope. But a lot of it is sensing. How does it know where it is in three-dimensional space?’
There is a connection to the microbiome. ‘We’ve got chemically aware robots. They are able to sniff chemistry. Part of that chemistry is microbial, so it all comes full circle.’
Another research line is robots for steering microbes. ‘We are trying to build robotic bacteria that we can steer to deliver drugs where we want them. So we work with robots on a big scale, and on the nanoscale. All that work is done with Imperial.’
He also has a start-up to develop holographic imaging for brain surgery. ‘In a stroke patient, the surgery pulls the clot out of the brain. It’s super difficult to fish out. Often neurovascular radiologists make that decision looking at 2D screens, rendering 3D in real time. We project the 3D as a hologram.’ The really clever bit, says Kinross, is to compute the location of the extraction wire as it passes through the brain. ‘It’s like the navigation app Waze for the brain.’ The hologram is generated by a commercial headset, currently the Apple Vision Pro. ‘Our partnership with NVIDIA really unlocked it,’ he says. ‘The computational load is too much for the cloud. We need GPUs running locally. It’s on the App Store now, as Medical iSight.’
It’s a broad sweep of careers. Which is the point, he stresses. ‘My PhD was in computational biology. I speak a bit of a lot of languages, microbiology, clinical medicine, and I’m interested in engineering. My gift, if I’ve got one, is to translate across multidisciplinary teams.’
What does he do?
Naturally, it’s impossible to talk to Kinross and not ask the obvious – what does he do for his own gut microbiome?
‘I eat much more fibres and prebiotic fibres. I don’t have a regular prebiotic because I don’t really think I need one. I became vegetarian. I’ve changed my stance because I’m a bit lazy. I’m now a vegetarian unless someone’s cooked meat for me, because it’s polite.’
The real key to good gut health, he says, is a holistic view of life: ‘Medicine is grounded in 19th- and 20th-century ways of thinking, very siloed. We don’t think in terms of systems. Many of our specialists work on a single organ. The evolution is towards how everything is ultimately connected.’
So while supplements and diet are good, Kinross’ recommendation is to get away from screens and modern life.
Get into nature, walk in the forest, swim in the sea and spend time with friends. Make your kids play outside. For a relentless researcher, it’s an unexpected message. If you follow the science, the best strategy is to put on your hiking boots and enter the wilderness. Your microbes will thank you for it.
Eliot Ward, Partner and Patent Attorney, at Mewburn Ellis comments:
“Activity and investment in this sector is booming again with industry insiders talking of a 'second wave' of opportunities. So it is a huge privilege to have Dr James Kinross share his fascinating insights with us at this time. New tools such as AI and omics integration (opening up new windows on the combined 'holobiome' of microbiome and host) are shedding light on the causality underlying the associations that were observed in the 'first wave'. All this will lead to amazing discoveries - and commercial opportunities. Developing a sharp IP strategy is of course crucial to protect your opportunities in this complex, fascinating field, which, in turn, means working with advisors who really understand it!"
Written by Charles Orton-Jones.
