Postbiotics Revolution: How to Start a New Era of Gut Health?

Each of these substances has its own role, sometimes triggering interactions with other species, and more often interacting directly with our bodies through the gut.

If we compare the gut microbiome to a busy intersection, then postbiotics are like the traffic police directing the roads. Tim Spector from King's College London says, 'Microorganisms are crucial to your health simply because they produce amazing things, namely these postbiotics.'

So far, much of the work identifying and exploring the potential of postbiotics has been done through cell or animal experiments, but there have also been some encouraging findings in humans. Take short-chain fatty acids as an example; these are metabolites produced by microorganisms in the colon when they consume hard-to-digest fibers, such as inulin found in foods like leeks, bananas, and asparagus.

Among them, a short-chain fatty acid called butyrate seems particularly useful. It interacts with immune cells and helps maintain the balance of our immune system, attacking any harmful bacteria that attempt to invade the gut while tolerating beneficial bacteria.

A lack of butyrate is associated with food allergies, and recent studies suggest that this metabolite plays a role in establishing food tolerance in the early years of life. It also helps keep the gut wall strong and reduces inflammation that can lead to obesity and gut diseases.

Clinical trials have shown that butyrate can serve as an effective adjunct therapy for ulcerative colitis, and butyrate-containing enemas can treat diversion colitis, which may occur when part of the gut lacks nutrients after surgery.

There is just one problem. Wojciech Feleszko, a pediatric immunologist at the Medical University of Warsaw, states, 'Butyrate smells like farts.' Therefore, taking butyrate directly is a challenge.

However, researchers at the University of Chicago have encapsulated this substance in spherical containers called 'micelles' to treat food allergies, which has shown very promising results in mice. The researchers hope their tiny, tasteless capsules can treat or even prevent allergies.

Another promising postbiotic example is equol—a metabolite produced when certain gut bacteria break down compounds in soybeans.

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Research on postbiotics is gradually shifting towards their potential as consumer products. Postbiotic supplements can already be found in health food stores and online in the UK and the US. The question is, to what extent do they work?

Take urate (UA) as an example. UA is a metabolite produced by our gut microbiota when they feed on foods like walnuts, pomegranates, and strawberries. This substance is believed to help maintain mitochondrial function, which declines with age and is associated with various aging-related issues.

Not everyone's gut microbiome can produce this metabolite from food, which has sparked interest in developing an oral supplement. A clinical trial conducted by a Swiss company called Amagentis showed that taking UA supplements could improve mitochondrial health in older adults, enhance leg strength, and alleviate osteoarthritis pain. These findings led to the launch of the first UA supplement—Mitopure—in 2020. However, ensuring mitochondrial health doesn't come cheap—a two-month supply of capsules costs $200.

Meanwhile, other researchers are focusing on using dead bacteria to improve gut health. Although this sounds a bit counterintuitive, bacteria don't necessarily have to be alive to be helpful. For example, Akkermansia muciniphila, a microbe that feeds on gut mucus, is often found in the microbiomes of slim, healthy young people. In contrast, levels of this bacterium are lower in individuals with obesity, type 2 diabetes, and irritable bowel syndrome. Studies have shown that supplementing mice with Akkermansia can prevent them from becoming obese.

To explore the potential effects of Akkermansia as a human postbiotic supplement, Patrice Cani and his colleagues at KU Leuven in Belgium conducted a clinical trial with 32 overweight or obese volunteers. The study showed that, compared to those taking a placebo, both dead and live bacteria could improve insulin sensitivity, thereby reducing the risk of type 2 diabetes, lowering blood cholesterol, and reducing weight.

The team even identified a protein on the surface of this bacterium, which they believe is a key factor in its effects. Two researchers involved in the trial founded a company called Akkermansia, which recently launched a supplement containing inactivated Akkermansia to help people control their weight and reduce the risk of cardiovascular disease and type 2 diabetes.

Research on dead bacteria or microbial metabolites has several practical advantages. Unlike probiotics, you don't have to store them under perfect conditions to maintain bacterial viability, nor do you have to worry about them growing uncontrollably in the gut. This means you can control the dosage more precisely, and there are fewer safety concerns.

However, Gregor Reid, an emeritus professor at Western University in Ontario, Canada, states that we need more evidence to prove that postbiotics make our gut healthier.

The lack of high-quality trials is hindering the industry's development. In 2019, an international group of scientists unanimously agreed that a product must be proven to have health benefits in controlled, high-quality trials to be designated as a postbiotic product. Reid says there are not many supplements on the market with human data to prove their benefits.

"Consumers need to know what they are buying and what they can expect it to do. Unfortunately, the commercial understanding of new terms is so fast that it has outpaced science, but the results could be completely nonsensical."

Schellekens states that more importantly, supplements only work when there is something that needs fixing. For example, in Western countries, about 25% of women have the microbes capable of converting soy into equol. Therefore, only the other 75% need to take supplements.

Currently, diet may be the best way to obtain postbiotics. The usual advice is to eat more plant-based foods and avoid overly processed foods. It is generally believed that consuming fermented foods (such as yogurt, pickles, miso, kombucha, and kefir) is beneficial because these foods contain live bacteria that can produce postbiotics. However, Hill says that even so, this is just a common belief, and there is not enough evidence to support it.

"Of course, fermented foods seem to be part of most healthy diets around the world, but we do not have direct evidence that this is because fermented foods contain bacteria, whether the bacteria are alive or dead. We are trying to find evidence in this area."

He said another issue is that, unlike our heart or liver, there are no reliable biomarkers for gut health. Hill said, "If we could digitally assess the state of the microbiome in our bodies, then we could see whether every action we take improves gut health, but we haven't done that yet."

Despite the many obstacles, Schellekens remains hopeful that the postbiotic revolution will bring new products. She said, "We have a natural microbial factory that can produce a lot of things that are beneficial to us. This is a huge untapped resource."

Original link:https://www.newscientist.com/article/mg25634150-200-how-postbiotics-could-boost-your-health-and-even-help-reverse-ageing/