What Are Postbiotics?

By Noelle Patno, PhD, Bened Life Chief Science Officer

While you may be familiar with probiotics, “live microorganisms that, when administered at adequate amounts, confer a health benefit on the host”,¹ you might not yet know about a whole host of other “-biotics” terms that have started popping up. Various products from pet foods to skin creams may contain “prebiotics” – carbohydrates that act as food for probiotics. Less commonly seen is the term “postbiotics,” which is currently, and confusingly, used to refer to a number of different substances (more on that later).

As more postbiotics find their way into supplements and foods, it’s important to understand what postbiotics are and the diversity of ways this term may be used. Here is a short course on the consensus definition and science of postbiotics.

Defining Postbiotics

Here is a simple way to think of postbiotics: postbiotics are “good” dead bacteria. And with a little more detail: Postbiotics are beneficial inactivated microbes with or without their parts. Let’s dig into the details of the definition and its controversy, because it’s actually more complicated than that.

The term “postbiotics” has been debated in the technical world over the last few years. Researchers and non-researchers have used the term “postbiotics” to describe probiotics that have been inactivated (dead good bacteria) or to describe products produced by bacteria or probiotics (stuff good bacteria make).

Neither of these definitions are the same as “good dead bacteria,” which is, in part, how the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined postbiotics in 2021.

Their technical definition of postbiotics is “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.² “Inanimate microorganisms” are basically dead cells. During inactivation, the dead cells may be split up into their parts (cell components or structures, like proteins or lipopolysaccharides that make up the cells).

However, cell byproducts – bioactive metabolites made by the microbes before they were inactivated – are not themselves defined as postbiotics by ISAPP, although such byproducts may be present within a postbiotic product.

There are two additional things to note here, for the science-lovers amongst us.

First, this definition does not require that postbiotics come from probiotics. For example, bacteria that may not act as probiotics (that is, they have not been tested and shown to provide a benefit, OR they did not provide a benefit when tested), could be inactivated and provide a benefit to human health only in their inactivated form.

Second, ISAPP doesn’t consider metabolites of probiotics to be postbiotics. Organic acids, vitamins, and short-chain fatty acids, such as butyrate, acetate or propionate, may be produced by some bacteria, but a “postbiotic” must include inactive cells or cell parts, not just metabolites.

One reason not to consider a molecule like butyrate as a postbiotic is that it can also be found independently from bacteria. Butyrate exists in butter fat, for example.^3,4 Vitamin K, which is important for blood coagulation as well as possibly bone and heart health⁵ can be sourced from bacteria or from green vegetables.

Examples of metabolites or bacterial products that do not, by themselves, meet ISAPP’s definition of postbiotics (but may be PART of a postbiotic) include:²

• Short-chain fatty acids produced by bacteria, such as butyrate
• Vitamins produced by bacteria, such as vitamin K
• Organic acids including lactic acid
• Proteins, including antimicrobial peptides, bacteriocins, or enzymes secreted by bacteria

You may see butyrate and other products of bacteria still described as postbiotics since ISAPP only recently published this definition and it has not been universally accepted. Similarly, many items are currently called probiotics which do not fit the probiotic definition put forward in 2001 by the World Health Organization (WHO) and Food and Agriculture Organization (FAO).⁶

In summary, a postbiotic contains dead cells and may also contain other components or metabolites of the live microbes from which they are derived.

How to Identify Postbiotic Supplements

Because the term “postbiotic” is not very familiar to the general public yet, many postbiotic products may not be clearly labeled as such on the bottle. Words to look for that indicate a postbiotic include: heat killed (HK), heat inactivated (HI), or heat treated (HT). For example, L. paracasei PS23 (heat treated), or HT-PS23, is a preparation of PS23 that has been treated with high heat until all cells are dead.

You may also see the term “cells” used in place of “CFU” (colony-forming units) when specifying the amount of a postbiotic strain on the label.

Are There Advantages of Post-biotics vs. Pro-biotics?

Postbiotics may be attractive for a number of reasons. 

For one, since they are not alive, they are not able to reproduce in the body. While the risk is very small that living probiotic cells taken by mouth would be absorbed into the bloodstream, or overgrow within the gut, postbiotics do not pose any such risk. This presumably makes them safer for people with a poorly functioning intestinal barrier. 

Postbiotics also do not need special protection to stay alive as they pass through the acidic environment of the stomach, since they are already dead. They also are typically shelf-stable, while some specialized probiotic strains are not. These stability advantages mean that postbiotics face fewer threats to their potency, and can even be incorporated into food products rather than taken in capsule form. 

The downside of postbiotics is that many of the procedures used to quantify and quality-check probiotics are not as robust currently for postbiotics. Quantification methods for dead cells are not standardized, and there are many different procedures in use. Also, there are many ways to inactivate a microbe, and the consistency of this procedure is not always assured within manufacturing and between the manufacturing process and the clinical studies used to understand if the postbiotic strain has a health benefit.

Ideally a postbiotic product would be controlled for quality in all of the following ways:²

• Identification of microbes before inactivation: Strain name, genetic sequence, and quantification by counting units
• Production of postbiotics: Use a well-characterized and successful inactivation method
• Quality control: Confirm that microbes are inactivated and no live microbes remain
• Description of postbiotic: Determine which components are included (inactivated microbes, structural components, metabolites, etc.) and quantification of those components
• Safety check: Are there any adverse reactions observed when taking it?
• Evidence of a health benefit: Complete a clinical study that is controlled and has a good study design, such as a randomized controlled trial (RCT)

As living organisms, probiotics have some advantages over postbiotics. Some probiotics may produce short-chain fatty acids, vitamins, or antimicrobial peptides within the gut, all of which may provide human health benefits. However, postbiotics cannot produce new compounds. However, postbiotics may already include some of those metabolites, if they are retained in the manufacturing process from the inactivation of the source microbes.

How Do Postbiotics Work?

Postbiotics can potentially act in many of the same ways that probiotics can.² They may interact with intestinal cells, immune cells, and bacteria in the gastrointestinal tract. Taking a postbiotic could result in one or more of these effects:^1,2

• Gut microbiota modification
• Intestinal barrier improvement
• Signaling through the host’s nervous system
• Metabolism modification
• Immune-modulation

Preclinical and clinical studies for a postbiotic of interest, for example HT-PS23, may reveal the mechanisms and/or beneficial effects it can provide. These may be the same or different from those of the same strain when it is alive. In fact, a postbiotic may be beneficial even if the live cells do not have any measurable health benefits.

Postbiotics Benefits

Many postbiotic products that may fall under ISAPP’s postbiotic definition have been tested in the lab and in the clinic. Like “live” probiotics, “dead” postbiotics appear to have strain-specific benefits – different strains have different benefits. The range of possible benefits of postbiotics is similarly wide-ranging, for intestinal health and beyond.

Several studies of certain postbiotics in the lab suggest they have antioxidant activities and other molecular mechanisms. Some studies with animals and/or humans have evaluated biomarkers found in blood and suggest an impact on immune function, or gut microbe populations, suggesting beneficial effects on the gut microbiome.⁷

As far as human health goes, clinical studies suggest that certain postbiotics may provide health benefits in stool consistency, cognitive function, sleep quality, or metabolic benefits, for example.⁷ Just as each probiotic requires evidence that it is a probiotic (provides a clinical benefit), a postbiotic is only “good dead bacteria” if clinical evidence supports that specific composition’s claimed benefit.

Know Your Pre-, Pro- and Postbiotics

There are a lot of “-biotics” out there, so how can you remember which is which? For the English majors out there, a way to distinguish between them is by focusing on their prefixes.

• “Pre”-biotics: “Before” the microbe. A prebiotic is a type of long starchy carbohydrate that is selectively used by certain microbes as a food source (such as the insoluble fiber in produce and whole grains). They are the only “-biotic” that is a molecule and not a cell or dead cell.⁸
• “Pro”-biotics: “Supporting” microbe. Probiotics are bacteria that “support” life by providing a health benefit.¹
• “Post”-biotics: “After” the microbe (think: after the microbe has been inactivated).²

Prebiotics and probiotics can make a great combination within a healthy diet. If you want to make your gut a welcoming place for beneficial live microbes like probiotics, it’s a good idea to provide them with a suitable food source (prebiotics). Prebiotics are likely to be present in most foods that contain soluble fiber. They can be taken as supplements; inulin is a very common prebiotic supplement that can be derived from chicory root or Jerusalem artichoke.

Postbiotics do not rely on prebiotics or probiotics to be beneficial, but can certainly be combined with them (unless otherwise indicated). For instance, you might take a probiotic supplement intended to help with gut health, a postbiotics supplement for mood, and regularly consume prebiotic foods that contain inulin (see here for a list of prebiotic foods).

So which should you choose: pre, pro, or post? Your choice of probiotic and/or postbiotic strains depends entirely on the health benefit you seek. But prebiotic foods are always a sound choice to incorporate into your regular diet, even if you don’t take any “-biotic” supplements.

The Future of Postbiotics

Postbiotics are a new area of microbiome therapeutics. As inanimate microbes, they do not require tightly controlled storage conditions, as probiotics do. This opens a wide range of opportunities for placing postbiotics in pasteurized and other foods to provide a health benefit that doesn’t require swallowing a capsule.

Yet the health benefits of probiotics are much more understood – the benefits of postbiotics (and how to characterize their biological activity) requires much more research. The definition of what a postbiotic is also continues to be hotly debated, particularly around calling metabolites like butyrate postbiotics.

Research is emerging on defining postbiotics, identifying how they work, and what benefits they will bring. Stay tuned!

Recommended reading:

What to Know about Neuralli Mood 

What Is the Gut-Brain Axis? How Your Microbiome Can Influence Wellbeing

What is HT-PS23? (HT L. paracasei PS23)

References:
1. Hill, C., et al. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi:10.1038/nrgastro.2014.66
2. Salminen, S. et al. Nat Rev Gastroenterol Hepatol. 2021;18(9):649-667. doi:10.1038/s41575-021-00440-6
3. Danudol, A., & Judprasong, K. Foods. 2022;11(22):3606. doi:10.3390/foods11223606
4. Månsson, H. Food Nutr Res. 2008;52:10.3402/fnr.v52i0.1821. doi:10.3402/fnr.v52i0.1821
5. Mladěnka, P. et al. Nutr Rev. 2022;80(4):677-698. doi:10.1093/nutrit/nuab061
6. https://www.fao.org/3/a0512e/a0512e.pdf.  Accessed March 22, 2024.
7. Vera-Santander, V. et al. Molecules. 2023;28(3):1230. doi:10.3390/molecules28031230
8. Gibson, G., et al. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. doi:10.1038/nrgastro.2017.75