Postbiotics: What are they, and do they work?

In recent years, scientists have shown that gut bacteria are important for good health. 

Having a thriving community of microorganisms is linked with positive health outcomes.

And as we plumb the depths together, we encounter new terms, like "probiotics," "prebiotics," "synbiotics," and the focus of this article: "postbiotics."

So, before we wade into in the science behind postbiotics, let’s get some terminology under our belts.

Pro-, pre-, syn-, post-

Probiotics are live microorganisms that can benefit your health when you consume large enough quantities. They appear in natural yogurt, some cheeses, and other fermented foods.

Prebiotics are compounds that feed your gut bacteria. For instance, types of dietary fiber abundant in plant-based foods nourish your gut bugs.

Synbiotics are a mix of prebiotics and probiotics. So, if you dipped some high-fiber fruit, like pear, into natural yogurt, you could consider that a homemade synbiotic.

Postbiotics are perhaps the least well-known. So, let’s dig in.

What are postbiotics?

In brief, postbiotics can be: 

• dead microorganisms

• bits of dead microorganisms

• compounds that microorganisms produce

• a cocktail of any of the above

To give you a couple of examples, postbiotics could include parts of bacterial cell walls or metabolites that bacteria produce as they break down your lunch. We'll give more examples later on.

In 2021, the International Scientific Association of Probiotics and Prebiotics defined a postbiotic as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.”

Before the term “postbiotics” was set in stone, scientists floated several alternatives. These included ghost probiotics and ghostbiotics. It seems a real shame that one of those didn’t stick.

Do postbiotics work?

Following hot on the heels of probiotics, prebiotics, and synbiotics, you can now purchase postbiotics in supplement form. Although postbiotics aren’t as widely available, their popularity is growing.

But can they benefit health? As it stands, there hasn’t been enough research to answer this question. And as we’ll see, they’re a varied bunch, so there’s a lot to unpack.

Before you get disheartened, there’s some interesting evidence, mostly from lab and animal studies, that some postbiotics may have potential. 

Below, we’ll dig into a few specific examples and introduce some exciting new terminology you can use to dazzle your friends. 

OK, let’s get started on that dazzling terminology.

What are cell-free supernatants?

In a nutshell, cell-free supernatants contain all the compounds that bacteria produce. 

To create cell-free supernatants, scientists grow bacteria in a dish. The microorganisms naturally produce a range of chemicals, also called metabolites, that leach into their surroundings.

Next, the scientists remove the live bacteria, and what’s left are cell-free supernatants. The bacteria are gone, but the metabolites they produce remain.

Different species and strains of bacteria produce different metabolites. So, supernatants vary, depending on the type of bacteria the scientists have used. They've studied a few of these supernatant combinations.

Supernatant lab studies

One lab study tested how cell-free supernatants from five species of “good” bacteria affected the cells that line your intestines. 

They found that metabolites from Lactobacillus acidophilus and L. casei had anti-inflammatory and antioxidant effects.

Others have found that supernatants can stop a disease-causing type of Escheria coli from invading the cells that line your gut. E. coli are a common cause of food poisoning.

Supernatant lamb study

A study in lambs found that supernatants from L. plantarum RG14 increased the surface area of lambs' guts by enlarging bumps called papillae that line the gut. 

An increased surface area helps the animals absorb more nutrients from their food. The scientists also noted lower levels of potentially pathogenic Enterobacteriaceae, such as E. coli.

We should be clear that besides the lamb research, these were all lab studies. Although this type of study is important, it doesn’t mean we'd see the same effect in humans. 

But if cell-free supernatants might reduce inflammation and slow cancer, they’re certainly worth pursuing. 

Short-chain fatty acids

As your gut bacteria feed on fiber, they produce short-chain fatty acids (SCFAs).

Experts now know that SCFAs have a wide range of beneficial effects. For instance, they can help control blood sugar, absorb minerals, and regulate inflammation.

Also, scientists have shown that the SCFA butyrate helps feed the cells that line your intestines, keeping them healthy.

But could SCFAs work as a postbiotic treatment? Unfortunately, there hasn’t been much research, but there are a few interesting examples.

For instance, in one study, scientists recruited 11 people with a form of inflammatory bowel disease (IBD) called ulcerative colitis. This condition is driven by inflammation in the gut. 

The researchers gave participants either a butyrate enema or a placebo enema for 8 weeks.

Those receiving the butyrate treatment had reduced markers of inflammation and improved symptoms. However, other studies haven’t found such large effects.

Other researchers have shown that SCFAs reduce appetite. Understanding this connection might help treat obesity.

And some scientists are even investigating whether SCFAs might help treat multiple sclerosis one day.

SCFAs produced in the gut are undoubtedly good for health. But it’s important to remind ourselves that investigations into SCFAs as a treatment or supplement are mostly limited to lab and animal studies. 

Supplements vs. diet

At this stage, it’s not clear whether taking SCFAs as supplements would provide the same benefits as SCFAs produced by gut bacteria as they ferment fiber-rich foods.

Unanswered questions abound. For example, in the gut, there are three main SCFAs: butyrate, propionate, and acetate, plus others in smaller amounts, like valeric acid.

As it stands, we don’t know what combination of these SCFAs might be most effective.

Dead bacteria

If you consume “good” bacteria while they’re alive, they’re considered to be probiotics. But once they’re dead, they’re postbiotics. And there’s some evidence that they might have health benefits.

A review published in 2020 looked at seven randomized controlled trials. Together, they included data from more than 1,700 children.

Overall, the authors concluded that heat-killed L. acidophilus LB reduced the duration of diarrhea. And heat-inactivated L. paracasei CBA L74 reduced the risk of developing diarrhea and sore throats.

However, the authors explain that the evidence isn’t particularly strong, and scientists need to do more research.

A study involving 280 older adults examined the effect of heat-killed L. pentosus strain b240 on the common cold. This type of bacteria commonly occurs in fermented foods.

The researchers gave some participants a placebo, others a low dosage of postbiotics, and the rest a high dosage of postbiotics. Participants took a capsule once a day for 20 weeks. 

Individuals taking the postbiotics were less likely to develop a cold, particularly those in the high-dosage group.

The authors concluded that heat-killed L. pentosus strain b240 “might be useful in improving resistance against infection.”

Other scientists have shown that heat-killed L. pentosus strain b240 increases the amount of immunoglobulin A in older adults’ saliva. 

This is telling because immunoglobulin A is the immune system’s first defense against pathogens trying to enter the mouth or nose. It might help explain why this postbiotic could protect against colds.

So, perhaps “good” bacteria don’t have to be alive to be helpful. Only time and more research will tell.

Exciting exopolysaccharides

Exopolysaccharides are sugar-based compounds released by microorganisms. They’re a varied bunch, and the food, cosmetic, and pharmaceutical industries have already found a wide range of uses for them. 

Some lab studies show that certain exopolysaccharides might enhance aspects of the immune response.  

A mouse study found that an exopolysaccharide produced by L. casei made the foot-and-mouth disease vaccine more effective by enhancing the animals’ immune response. 

And a study showed that kefiran, an exopolysaccharide produced by L. kefiranofaciens, reduced blood pressure and cholesterol levels in rats eating a high-cholesterol diet.

Once again, we don’t have a whole load of evidence.

Still, if exopolysaccharides can improve immune responses while lowering cholesterol, blood pressure, and cancer risk, that would be incredibly useful. But we’re not there yet.

Enzyme action

During metabolism, reactive oxygen species are produced. These chemicals can damage bacteria. 

But bacteria are nothing if not resourceful. To protect themselves, they evolved a suite of antioxidant enzymes. And some scientists think these enzymes might be useful as postbiotics.

For instance, a study in lambs found that postbiotics from some species of Lactobacillus increased antioxidant activity in the animal’s blood, gut, and liver.

Other studies showed that antioxidant enzymes from microorganisms reduce inflammation in a mouse model of IBD and prevent colon cancer in susceptible mice.

However, to date, there’s been little research testing individual antioxidant enzymes in animals.

Using fragments of the cell wall

Most bacteria are surrounded by complex cell walls. Some of their building blocks might act as postbiotics.

A major component of the cell wall is lipoteichoic acid. But how it might impact health is still up for debate.

Some research shows that it reduces inflammation, but other studies conclude that it doesn’t — and might damage tissues instead.

Still, scientists are interested in lipoteichoic acid, and some animal studies hint that it might help the immune system fight cancer. 

Researchers have been interested in muramyl dipeptide for many years. And some have focused on its potential to boost the immune system’s defenses against cancer. 

However, it tends to cause a fever, so this has limited its use. Researchers are tinkering with its structure to see if they can design a similar molecule that doesn’t cause this side effect.

Bacterial lysates

Bacterial lysates are made from broken-down bacterial cells. Of all the postbiotics mentioned in this article, only these are a mainstream treatment today.

Specifically, doctors prescribe them to prevent respiratory infections in people who regularly get infections. People can take bacterial lysates orally, nasally, or as an injection. 

In this case, the lysates come from bacteria that commonly cause respiratory infections.

Experts believe that they work via the gut-lung axis to bolster the immune system in the lungs.

After you take bacterial lysates, they reach your intestines. Once there, they stimulate dendritic cells, which are important players in your gut’s immune system. 

The dendritic cells then recruit white blood cells, which move around the body and end up in your respiratory tract. There, they trigger other immune cells, improving your immune defenses. 

There’s good evidence that bacterial lysates might help treat recurrent respiratory tract infections in children and reduce asthma symptoms.

There’s also evidence that they might improve symptoms of atopic dermatitis (eczema) in children.

How to boost postbiotics naturally

The evidence that postbiotics can work as a medicine or supplement is very limited. What we know is that having a thriving community of “good” gut bacteria will support your health. 

So, postbiotics that naturally occur in your gut are likely to be a good thing.

The simplest way to do this is through your diet. In brief, try to eat more fresh fruits and vegetables, beans, legumes, nuts, seeds, and whole grains. Add fermented foods to your diet, and only eat ultra-processed foods once in a while.

Regularly exercising and getting enough sleep can also help.

If you’d like more detail, we’ve published a deep-dive article on how to support your gut health and gut microbiome.

The takeaway

Currently, manufacturers can only add certain live bacteria to foods and medicines. In the United States, the Food and Drug Administration (FDA) has to deem these “generally recognized as safe.” 

Similarly, in the European Union, the European Food Safety Authority has the "qualified presumption of safety" classification. 

These are sensible restrictions — bacteria can cause infections, after all.

However, if a bacterium is dead, it’s no longer an infection threat. And compounds produced by bacteria aren’t infectious either. 

For instance, Faecalibacterium prausnitzii is considered a “good” gut bacteria. But it’s not “generally recognized as safe,” so it can’t be sold as a probiotic. 

However, experts believe that the butyrate and microbial anti-inflammatory molecule (MAM) produced by F. prausnitzii are responsible for some of its health effects. 

So, theoretically, a postbiotic including inactivated bacteria, butyrate, and MAM might benefit health.

As we’ve noted throughout this article — there’s promise, but research into postbiotics is still in its infancy. It’s certainly a topic to follow, though. It has real potential. 

For now, if you see a postbiotic on the shelves, it's unlikely to be a miracle cure.