Scientists are only just discovering the enormous impact of our gut health – and how it could hold the key to everything from tackling obesity to overcoming anxiety and boosting immunity.
If you want to learn more about what’s 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 your gut isn’t 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 in 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.” And, for all that the internet may be full of probiotic or wellness companies making big health claims about gut health, “We don’t really know how it works,” he says. At the risk of sounding like the late Donald Rumsfeld, there’s what we know, what we think we know, and an awful lot that we don’t yet have a clue about.
Your gut microbiome weighs about 2kg and is bigger than the average human brain. It’s 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 co-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 in 2020 by the European Bioinformatics Institute, which pooled more than 200,000 gut genomes to create a genetic database of human gut microbes, 70% of the microbial populations it listed – 2,000 species – hadn’t yet been cultured in a lab and were previously unknown.
Lots of things that people don’t think about, like depression or anxiety, are very clearly modified by your gut microbes.
“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 Professor Tim Spector, an epidemiologist and author of two books on dietary and gut health.
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 both inherited and essential, while others use superorgan, 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. 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.”
Studies suggest having a diverse population of gut microbes is associated with better health.
Studies suggest having a diverse population of gut microbes is associated with better health. But when human populations urbanize, microbial diversity declines. Professor 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 multi-generational loss of microbes that appear to be important for human health,” he 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. It’s difficult to prove epidemiologically – 100 years ago no one gave a crap about allergic diseases because globally 50m 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.”
Gut microbes do things the gut can’t do, liberating or synthesizing nutrients from food, especially from plants and their polyphenols, living off non-digestible substrates, producing thousands of metabolites – useful chemicals –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 US is just 10-15g. 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,” says Spector. (When he talks about junk food, Spector means most prepared and packaged foods – including things such as vegetarian lasagna.) “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. 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. 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,” says Kinross. 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.”
Pick a disease. The gut microbiome is associated with it.
“Everything we’re doing now is scratching the surface,” says Spector. “We are maybe 10% 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,” he says. “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.”
Humans want an easy answer on all this gut microbiome stuff, but the reality is that there's still so much we don't understand. Don't take anyone seriously who says otherwise.
The theory 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 doesn’t 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’re 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% of the same gut microbes). By feeding participants the same meals on different days, he was able to show that responses to the same meals also vary hugely between individuals, influenced by both the microbiome and genetics. This matters, he says, 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 doesn’t make sense in a world where two people’s blood glucose levels can be hugely different after eating the same slice of cake.
Microbiome testing has been around for a while, but it’s never been particularly useful as a way for people to understand what’s going on inside their bodies because not enough is known about what microbes do or how they interact. As Dr. 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.”
Microbiome testing has been around for a while, but it’s never been particularly useful.
Spector's team has identified 30 key microbes linked to specific foods and that they claim are indicators of health. Result of his PREDICT 1 study, co-created with a team at Harvard and the University of Trento, recruited over 1,000 people. The results were published in Nature Medicine.
While many microbiome scientists may 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 is yet licensed for medical use in the US or Europe). Professor 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,” he says. But he is curious about a blend he has already studied for its impact on IBS, called Symprove, and its potential as a treatment in hospitals for acute Covid. “We think of Covid as a virus of the lungs, but the microbiome of people with acute Covid can be altered very severely. 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 acute Covid patients treated with it might be less likely to end up in ICU or to die, and eight times less likely to suffer 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,” says Jack Gilbert. This bacteria seems purpose built to digest oligosaccharides in breast milk, sugars which 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 Africa and certain parts of Southeast Asia that aren’t developed have tons of bifidobacterium longum infantis. 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.”
One of the most exciting and far reaching applications of all this gut microbiome exploration might be 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 100m neurons. We also know 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 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,” she 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.”
*Red beets and corn are actually more standard approaches, but "Go Blue" if you must.