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IT IS 9.30am and you are feeling a bit off. You have just finished a round of antibiotics and know your gut microbes have taken a hit. You pop a pill and head out, safe in the knowledge that while the microscopic communities in your intestines may take a while to regroup, the health benefits they confer will be back up to speed much sooner. Welcome to the world of postbiotics.

As evidence piles up about the importance of our microbiome to our health, so too has the desire to boost it. First came probiotics, the live bacteria you need in your gut. Then there were prebiotics, or the foods these microbes need to thrive. Now, there is a new kid on the block: postbiotics, a catch-all term to describe dead bacteria and the products excreted by live microbes.

It turns out that postbiotics do a lot of the heavy lifting when it comes to the relationship between your gut microbiome 鈥� made up of bacteria, fungi and viruses 鈥� and good health. And by cutting out the go-between, you can sidestep many of the problems that come with trying to optimise gut health by other means. 鈥淭here鈥檚 excitement building around postbiotics,鈥� says Colin Hill, a microbiologist at University College Cork in Ireland. 鈥淚t feels like we鈥檙e at a nexus where this field is potentially going to explode.鈥� Certainly, lifestyle magazines and health food shops are extolling their benefits for everything from better skin and stronger muscles to stopping hot flushes and preventing diarrhoea. But what exactly are postbiotics, how do they work and are they really the easy path to perfect gut health we have all been waiting for?

Let鈥檚 start with the 100 trillion bacteria, fungi and viruses that live in and on our bodies, mainly in the gut. We know this microbiome is linked to good physical and mental health. The relationship is mutually beneficial: in exchange for providing food and board, beneficial gut microbes support our immune system, protect us from bad bacteria and help us digest food. They also affect our energy levels, alter the way we store fat and change how we respond to hormones that make us feel hungry or full, says . Recent evidence suggests that the microbiome also affects the brain, has an influence on our behaviour and even plays a role in ageing.

Our gut microbes, though, are sensitive souls. The balance of what is living in our intestines and the good they do is affected by our diet, our age and where we live, and it can be knocked off the rails by stress and drugs such as antibiotics or chemotherapy. This is where pre and probiotics come in. For several decades now, they have been marketed as a way to repopulate your gut to maintain microbial diversity and keep it healthy. Your microbiome is big business: in 2021, the , and growing.

Pre and probiotics have a lot going for them. There is evidence that taking probiotic supplements can help after a course of antibiotics, and have a and its length. According to the Alliance for Education on Probiotic Products, which publishes an independent review called the (a list of supplements available in the US and Canada and their dosage backed up by data in humans), there is also some evidence that probiotic supplements can help with traveller鈥檚 diarrhoea, constipation, Helicobacter pylori and Clostridium difficile infections, thrush and mastitis. Use of prebiotic supplements, which are, in essence, food for beneficial gut bacteria, has less evidence behind it, but studies suggest that they may regulate our desire to eat by and , which is good for bone health.

Even so, attempts to boost our microbiome with pre and probiotics aren鈥檛 without issues. For a start, we don鈥檛 yet know enough about what gut microbes feed on, while studies have shown that live microbes in supplements don鈥檛 always survive the journey through our digestive tract. Then there are problems that come from dealing with live microbes. They must be carefully stored, as many are sensitive to heat or humidity, and dosing isn鈥檛 an exact science because it is hard to know how many will be alive at any one time. While live probiotic bacteria causing illness is rare, this does occur and can be serious for people with weakened immune systems.

Your gut鈥檚 pharmacy

Enter postbiotics. While their exact definition is debated, they are generally considered to be one of three things: dead microbes, which are more useful than you might imagine; fragments produced when microbes break down; and chemicals such as enzymes, vitamins, polysaccharides and short-chain fatty acids that microbes have secreted. Each exerts its own effect, sometimes by triggering interactions with other species or, more often, by interacting directly with our body via the gut.

If the gut microbiome is like a natural pharmacy, postbiotics are the medicines it dispenses. 鈥淢icrobes are crucial for your health only because of the amazing things that they produce, which are these postbiotics,鈥� says Tim Spector at King鈥檚 College London.

So far, much of the work identifying and exploring the potential of postbiotics has been done by experimenting on cells and animals, but there are some promising findings in people too. Take short-chain fatty acids, for instance. These are metabolites produced when microbes in our large intestine consume indigestible fibre, like inulin found in foods such as leeks, bananas and asparagus.

One short-chain fatty acid called butyrate seems to be particularly helpful. This interacts with immune cells to help maintain our immune system鈥檚 fine balance between tolerating the good bacteria in our gut and reacting to any bad bacteria that try to muscle in. A lack of butyrate has been implicated in food allergies and recent work has suggested that this metabolite plays a role in developing food tolerances in the first years of life. It also keeps the gut wall strong, reducing inflammation that contributes to obesity and bowel diseases. Clinical trials suggest that butyrate can be a useful supplementary therapy for ulcerative colitis, and enemas that contain it can treat diversion colitis, which can occur when part of the intestine is starved of nutrients following surgery.

A bad smell

There is just one problem. 鈥淏utyrate smells like a fart,鈥� says Wojciech Feleszko, a paediatric immunologist at the Medical University of Warsaw, Poland, and author of a . Taking butyrate directly therefore is a challenge. But researchers at the University of Chicago have encapsulated the substance in spherical containers called micelles to , demonstrating promising results in mice. They are hopeful that their tiny, odourless capsules could treat or even prevent these allergies in people.

Another example of a promising postbiotic is equol, produced when certain gut bacteria break down a compound in soya. It resembles the chemical structure of the female sex hormone oestrogen and some studies have . A small trial also found it could reduce the severity of menopausal hot flushes.

The ability of some postbiotics to modulate the immune system 鈥� by ramping it up or down 鈥� also means they have been investigated as a promising adjunct to cancer therapies. For instance, studies have shown that certain postbiotics can help reduce side effects of immunotherapies, which boost the immune system to fight cancer, while others seem able to suppress tumours. with different types of cancer cells has shown that the waste products secreted by Lactobacillus bacteria can trigger the death of cancer cells or reduce their ability to invade other tissues.

Better ageing

Research into postbiotics hasn鈥檛 only focused on how it can be used to help treat specific clinical conditions, there is now an increasing volume of work on its potential as a consumer product. Postbiotic supplements can already be found in health food shops and online throughout the UK and US. The question is, to what extent do they work?

Take urolithin A (UA), a metabolite produced when our gut microbes feed on things like walnuts, pomegranates and strawberries. This substance is thought to help maintain functioning mitochondria, which power our cells, something that declines with advancing years and which is implicated in various problems associated with ageing.

Not everyone has the right mix of gut flora to produce this metabolite from food, which led to interest in developing an oral supplement. In clinical trials, a Swiss company called Amazentis has shown that , increase leg strength and alleviate the pain of osteoarthritis. These findings led to the launch of , the first UA supplement, in 2020. The promise of mitochondrial wellness doesn鈥檛 come cheap, though 鈥� two months鈥� worth of their capsules costs $200.

Meanwhile, other researchers are focusing on the beneficial effects of using dead bacteria to supplement gut health. As counter-intuitive as it may sound, bacteria don鈥檛 have to be alive to be helpful. For instance, Akkermansia muciniphila is a microbe that feeds off the gut鈥檚 mucous lining, and regularly turns up in the microbiomes of slim, young people with no known health conditions. Conversely, lower levels are found in people with obesity, type 2 diabetes and irritable bowel diseases. Research showed that supplementing mice with A. muciniphila protected them from becoming obese.

Since A. muciniphila had never been investigated as a postbiotic supplement in people, Patrice Cani at the Catholic University of Louvain in Belgium and his colleagues conducted a clinical trial involving 32 overweight or obese volunteers. It showed that regardless of whether the bacteria were dead or alive, they led to improved insulin sensitivity, which can reduce the risk of type 2 diabetes, lower blood cholesterol and lower body weight compared with people who took a placebo. The team was even able to identify a protein on the surface of this bacterium that they think is responsible. Two researchers involved in the trial have since created the , which last month launched a food supplement containing deactivated A. muciniphila, as a means to help people manage weight and reduce their risk of cardiovascular disease and type 2 diabetes.

Practical advantages

Working with dead bacteria or waste products from microbes offers several practical advantages. Unlike probiotics, you don鈥檛 have to store them under perfect conditions to keep the bacteria alive and you don鈥檛 have to worry about them growing out of control in the gut. This means you can be more certain of the dose, and there are fewer safety concerns.

However, Gregor Reid, an emeritus professor at Western University in Ontario, Canada, says that we need more evidence that postbiotics will make it intact to our guts.

A lack of high-quality trials also plagues the industry. In 2019, an international group of scientists agreed that for a product to be designated as a postbiotic, it must be proven to confer a health benefit in a controlled, high-quality trial. Not many supplements currently on the market have the human data to warrant this label, says Reid. 鈥淭he consumer needs to know what it is that they are buying and what they can expect it to do. Unfortunately, the commercial side is so fast at catching on to new terminologies, that it gets ahead of the science and the result can be total nonsense.鈥�

What鈥檚 more, supplements are only going to work if there is something to fix, says Schellekens. For example, about 25 per cent of women in Western countries have the right set of microbes to turn soya into equol, the metabolite that improves oestrogen-linked problems. A supplement only makes sense for the other 75 per cent.

For now, diet may be the best route to postbiotic benefits. The usual advice stands: eat diversely with plenty of plant-based fare and steer clear of ultra-processed foods. It is accepted wisdom that eating fermented foods, such as yogurt, kimchi, miso, kombucha and kefir, is good for us as these contain live bacteria that can make postbiotics. But even this is more common sense than evidence-based, says Hill. 鈥淐ertainly, fermented foods seem to be a part of most healthy diets around the world, but we don鈥檛 have direct evidence that this is because they have bacteria in them, alive or dead. This is something we are trying to generate the evidence on.鈥�

He says that part of the problem is that there are no reliable biomarkers for gut health, unlike for our heart or liver (See 鈥淲hat does your poo say about you鈥�). 鈥淚f we had numerical readouts for the state of your microbiome, we could then see whether we鈥檙e improving it with every action you take, but we鈥檙e not there yet,鈥� says Hill.

Despite the hurdles, Schellekens is hopeful that the postbiotic revolution will lead to new drugs. 鈥淲e have a natural factory of microbes that can make loads of things that are beneficial for us. It鈥檚 just a huge untapped resource,鈥� she says. Spector鈥檚 money is on postbiotics that could support cancer immunotherapy. 鈥淵ou鈥檝e got this whole pharmacy waiting inside your gut,鈥� he says. Now the challenge is to learn how to harness it.