If you want to learn more about what is going on in your gut, the first step is to turn your poo blue. How long it takes for a muffin dyed with blue food coloring to pass through your system is a measure of your gut health. The median is 28.7 hours. Longer transit times suggest that your gut is not as healthy as it could be.
We are only now beginning to understand the importance of the gut microbiome. Could this be the start of a golden age for gut-health science?
“The gut microbiome is the most important scientific discovery for human healthcare in recent decades,” says James Kinross, a microbiome scientist and surgeon at Imperial College London. “We discovered it — or rediscovered it — in the age of genetic sequencing less than 15 years ago. The only organ which is bigger is the liver.”
Illustration: Mountain People
And, for all that the Internet might be full of probiotic or wellness companies making big health claims about gut health, “we don’t really know how it works,” Kinross says.
At the risk of sounding like former US secretary of defense Donald Rumsfeld, there is what we know, what we think we know, and an awful lot that we do not yet have a clue about.
Your gut microbiome weighs about 2kg and is bigger than the average human brain. It is a bustling community of trillions of bacteria, archaea, fungi and viruses, containing at least 150 times more genes than the human genome. We are filled to the brim with microbes, which form microbiomes on our skin, in our mouths, lungs, eyes and reproductive systems. These have evolved alongside us since the beginning of human history, but the gut’s is the largest and most significant for our short and long-term health. It is massively complex and its residents vary enormously from person to person.
According to a study last year by the European Bioinformatics Institute, which pooled more than 200,000 gut genomes to create a genetic database of human gut microbes, 70 percent of the microbial populations it listed — 2,000 species — had not yet been cultured in a lab and were previously unknown.
“It’s a vital organ in your body and you need to look after it. If you do that, it will look after you,” says Tim Spector, an epidemiologist at King’s College London, author of two books on dietary and gut health, and cofounder of the ZOE app, initially developed as a gut health program, but temporarily re-engineered as a COVID-19 symptom tracker early in the pandemic.
Whether the gut microbiome can be considered an organ is still up for discussion — many microbiome scientists call it an organ, given that it is inherited and essential, while others use super organ, supporting organ or microbial organ.
“Lots of things that people don’t think about, like depression or anxiety, are very clearly modified by your gut microbes,” Spector says. “Appetite and ability to digest food are modified by gut microbes. The key finding recently is the link with the immune system.”
“Basically, the gut microbiome is controlling it, sending signals, because most of your immune system is in your gut, helping you fight infections, such as COVID and early cancers, that the immune system is picking off,” he says.
Studies suggest that having a diverse population of gut microbes is associated with better health.
However, when human populations urbanize, microbial diversity declines.
Jack Gilbert is an award-winning microbiome scientist at the University of California San Diego and author of Dirt Is Good.
“Over the past 80 years and since the dawn of antibiotics, there has been multigenerational loss of microbes that appear to be important for human health,” Gilbert says. “They’re passed from mother to child [during birth, via breastmilk and skin contact] throughout the generations, but at some point in the last three or four generations, we lost some. We’re not entirely sure if the cause was our lifestyle, our diet, cleanliness in our homes or the use of antibiotics. We’re also missing certain immune stimulants that people in the developing world have plenty of.”
What are the implications of this?
“Those two things combined may be underlying a large proportion of the chronic diseases our society is suffering from — asthma, food allergies, atopic diseases and auto-immune disorders,” he says. “It’s difficult to prove epidemiologically — 100 years ago no one gave a crap about allergic diseases because globally 50 million people a year were dying of infectious diseases, but over the past 50 years of good scientific record keeping, we’ve seen a significant increase in those disorders [alongside] this loss of microbial diversity in our guts.”
FUNCTIONS
Gut microbes do things the gut cannot do, liberating or synthesizing nutrients from food, especially from plants and their polyphenols, living off non-digestible substrates, producing thousands of metabolites and making vital short-chain fatty acids that are involved with immunity, with keeping the gut and colon healthy, with moderating the body’s inflammatory responses and with the metabolism of glucose.
To do this, microbes need about 30g of fiber a day, but the average intake in the UK is just 10g to 15g. Is this why modern, low-fiber, ultra-processed, high-sugar diets seem so problematic for human gut health?
“It’s very hard to know exactly what it is in junk food that is causing a problem,” Spector says.
When he talks about junk food, Spector means most prepared and packaged foods — including things such as vegetarian lasagne.
“It’s not the fat, carbs and protein, it’s the extra chemicals. The data is probably best for artificial sweeteners that are derived from things like paraffin and the petrol industry, so our bodies and our microbes are not used to breaking them down, but it could be other stuff, like the enzymes you don’t get on the label, or emulsifiers,” he says. “There are few studies on emulsifiers, and nearly all in animals, but they show that you get reduced diversity and more inflammatory microbes. The idea is that they’re doing the same as they are in cooking: sticking your microbes together, creating an emulsion.”
“Or it could be the lack of fiber and the fact that everything is refined,” he says. “We haven’t nailed it down, but I think it’s safe to say that ultra-processed foods are bad for your gut microbes and we should avoid eating them regularly.”
The great opportunity — but also the great difficulty — of gut microbiome science is that poor gut health is associated with such a vast range of conditions, from obesity and degenerative brain diseases to depression, inflammatory bowel disease and chronic inflammation.
“The microbiome is associated with everything: Pick a disease, it’s associated,” Kinross says. “The microbiome is like a convergent science — you have to be an ecologist, a geneticist, a bioinformatician, a clinician and an epidemiologist, to try to make sense of it.”
“Everything we’re doing now is scratching the surface,” Spector says. “We are maybe 10 percent of the way there, because every week we’re discovering something new. Humans want an easy answer [to improve our gut health], but you shouldn’t take anyone seriously who doesn’t say it’s complicated.”
“There’s a massive industry that needs a simple message to sell its products. They want to say all you’ve got to do is eat this bar, this yoghurt or this protein drink,” he says.
Spector does have skin in this game. He and Jonathan Wolf, a machine-learning and data science expert, founded ZOE four years ago with the aim of creating personalized diets based on what an individual’s specific gut microbes needed.
It has already launched in the US and later this year people in the UK will be able to buy into the ZOE testing process.
The price for the UK program has not yet been finalized, but in the US it costs US$360 for six months.
The #bluepoopchallenge, started by ZOE, is free. The recipe for blue muffins, which hundreds of thousands of people have already used to track their digestion, is on the ZOE Web site.
The theory behind ZOE is that our varying gut microbes explain, at least partially, the big differences in individual responses to food: why one person who eats a lot of fat or sugar does not put on weight, while another does, or why some of us can tolerate particular foods better than others, even why particular people become obese.
If we knew which microbes were associated with a higher risk of obesity — because they are more efficient at accessing calories, perhaps — or which best protect brain health, then we could tailor our diets to feed them.
Spector’s 30-year-long study of 15,000 twins, TwinsUK, and his PREDICT studies have shown that even genetically identical people respond to the same foods very differently. Our microbiomes are so variable that twins share only 30 percent of the same gut microbes.
By feeding participants the same meals on different days, he showed that responses to the same meals also vary hugely between individuals, influenced by the microbiome and genetics.
MANTRA-BUSTER
This matters, because our response to food is linked to our risk of heart disease, type-2 diabetes and obesity, but also because it blows apart the tired and useless mantra “calories in, calories out,” which does not make sense in a world where two people’s blood glucose levels can be hugely different after eating the same slice of cake, the ZOE team says.
Microbiome testing has been around for a while, but it has never been particularly useful as a way for people to understand what is going on inside their bodies, because not enough is known about what microbes do or how they interact.
As Megan Rossi, AKA the Gut Health Doctor, a dietitian and research fellow at King’s College London and author of Eat Yourself Healthy, puts it: “I see patients in clinic with [microbiome] tests, and it would really help me to be able to use them to get patients better, but they just don’t have clinical translation.”
“I absolutely believe in the future they will, but we’re not there yet,” Rossi says.
Spector hopes that his tests — which do not just test for microbes, but also assess blood fat and blood glucose responses to specific foods — will change this.
“We’re just starting to get to the point where we can suggest individualized foods. This is not just isolated microbiome testing,” he says. “We have trials in place to quantify this, but the initial results are exciting, with nearly everyone reporting weight loss and improved energy levels without any calorie counting or traditional weight loss methods.
“Previous microbiome tests have been sub-optimal, [but the] ZOE approach is completely different: using state-of-the-art sequencing allows us to detect species and strains and find strong associations between these microbes and both foods and health,” he says.
This is done via algorithm, as Wolf explains, combining his machine-learning with the microbiome science.
However, “if we were going to do this, we were going to do it the right way; to carry out what’s turned out to be the largest in-depth, nutritional science study in the world, in order to collect the raw data for the machine learning,” Wolf says.
“And that meant getting thousands of people to do very intensive studies. We identified 30 key microbes that are indicators of health and linked to specific foods,” he says of his PREDICT 1 study, co-created with a team at Harvard University in Massachusetts and the University of Trento in Italy, involving more than 1,000 people and published in Nature Medicine.
If our microbes are so important, can we note just package up the right ones and put them in a pill?
John Cryan is chair of the department of anatomy and neuroscience at University College Cork in Ireland and principal investigator at the APC Microbiome Institute.
“We will get strains of bacteria to have beneficial effects,” Cryan says.
However, he laughs when I ask him how he feels about probiotics.
“That’s like asking me: ‘Do I like drugs?’ If I have a pain in my head, I want to take a drug that has efficacy for headaches. I wouldn’t just randomly pick one, but that’s what we’re doing with probiotics right now,” he says. “The science needs to catch up. We’re lumping them together as if they’re the all the same thing, but, like drugs, they may do very, very different things.”
“We need to get precision into probiotics and then I can be excited about them, but most of what’s out there is complete nonsense,” he says.
While many microbiome scientists do not have much time for the commercial probiotics industry, there is growing interest in what are now called live bio-therapeutics — probiotics designed and tested to be used clinically.
None are yet licensed for medical use in the US or Europe.
Ingvar Bjarnason is a gastroenterologist who has conducted double-blind, placebo-controlled studies on specific probiotic blends.
“There is no data whatsoever for the vast majority of the probiotics on sale,” Bjarnason says.
However, he is curious about a blend called Symprove that he has already studied for its impact on irritable bowel syndrome and its potential as a treatment in hospitals for acute COVID-19.
“We think of COVID as a virus of the lungs, but the microbiome of people with acute COVID can be altered very severely,” he says. “Very ill people with COVID have a cytokine storm where they have multi-organ failure due to an enormous amount of really strong inflammatory markers. The suspicion is this inflammation may come from the gut, and when the gut has been examined in acute COVID patients, it is abnormal.”
A very small Italian study using a similar commercial probiotic, Sivomixx, piqued his interest after it suggested that acute COVID-19 patients treated with it might be less likely to end up in intensive care or die, and eight times less likely to have respiratory failure.
Bjarnason is hoping to start a larger study in the next few months.
Several other gut bacteria are also being studied as biotherapeutics.
“One of the bugs that appears to have disappeared from Europeans, North Americans and Chinese people over the last 50 years, is Bifidobacterium longum infantis,” Gilbert says.
This bacterium seems purpose-built to digest oligosaccharides in breast milk, sugars that babies born in developed areas simply poo out.
“That’s why in the Western world, baby poo is sloppy, whereas in the developing world, baby poo comes out pretty solid, more like adult poo, because their breast milk is being digested by the bacteria in their intestine — kids growing up in Africa and certain parts of Southeast Asia that aren’t developed have tonnes of Bifidobacterium longum infantis,” Gilbert says. “If we put it into a mouse and feed it breast milk, it digests all the sugars. There are clinical trials ongoing, putting this bug back into children, especially in preterm infants in neonatal intensive care units, to see what impact it has.”
The final frontier for gut microbiome exploration is its relationship with our brains, something the new fields of nutritional psychiatry and psychobiotics are digging into.
We already know the gut has its own nervous system, the enteric nervous system, and contains 100 million neurons.
We also know that the gut-brain axis, via the vagus nerve, shoots neurotransmitters produced within the gut around the body and to the brain, which is why Cryan’s lab has studied the impact of particular bacteria on sleep and how certain types of fiber can improve complex cognitive processes.
Kimberley Wilson is a chartered psychologist and author of How to Build a Better Brain. She uses nutrition as part of her treatment plans.
“The short-chain fatty acids produced from microbial fermentation of fiber [in the gut] are quite similar to some mood-stabilizing prescription drugs,” Wilson says. “Some of the association that we see between healthier diets and better brain health could be because your microbes are producing psychoactive substances from your diet to help stabilize your mood. In the future, we might actually prescribe certain types of fibers for certain mental health conditions.”
For now, she simply prescribes a lot more fiber to feed what many scientists now consider our second — much larger — brain.
“The more fiber you eat, the more substrates the microbiome has available. And the better off we’re going to be, psychologically. I think that’s incredible,” she says.
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