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Breaking Down “Biotics”

Category: Educational Articles

“Biotics” (which means relating to or resulting from living things) is a term we have come to hear a lot about over the past few decades and has increasingly been used to describe a plethora of different health-promoting ingredients relating to beneficial microorganisms.

Prebiotics, probiotics, synbiotics and postbiotics – what do each of these do and how are they different from each other? All of these play an important role to your gut microbiome and to your overall health.

Let’s start with what the gut microbiome is. According to the Encyclopedia of Cell Biology, the gut microbiome is “the collection of microorganisms including bacteria, archaea [also known as ‘the third domain of life’], viruses, and fungi found within the gut and their overall genetic information.” A flourishing and balanced microbiome is key to optimum health.

We’ve put together some summaries of how scientists are defining the different “biotic” categories and what that means:

Probiotics:

The definition of probiotics as set forth by the FAO and the World Health Organization (WHO) is generally accepted and acknowledged by the majority of the scientific community and is endorsed by the International Scientific Association for Probiotics and Prebiotics (ISAPP).

  • They agree that probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”

Let’s unpack this definition together. First, probiotics, must be microorganisms. Probiotics, therefore, can include organisms other than just bacteria from the well-known Lactobacillus or Bifidobacterium genera. Bacteria, fungi, or protozoa from any genera can technically be probiotics provided they also meet the other requirements of the FAO/WHO definition. Spore-forming soil bacteria (like Bacillus subtilis), novel yeasts (like Saccharomyces boulardii), and bacteria commonly found in the healthy gut (like Akkermansia muciniphila and Faecalibacterium prausnitzii) are all examples of probiotic potential.

Secondly, probiotics must be live. If microorganisms are dead at the time of use or before they reach the site of action in the body, no matter how effective they are, they cannot be called probiotics. There are many microorganisms that cannot currently be considered probiotics simply because they cannot be kept alive during manufacture or storage.  Many of the potentially beneficial bacteria that naturally live in the healthy human gut (e.g., Akkermansia muciniphila and Facalibacterium prausnitzii) have not been commercialized as probiotics because of their extreme sensitivity to oxygen and other stressors. This sensitivity makes them die when manufactured and stored under typical conditions. Even many common Lactobacillus and Bifidobacterium strains die-off when exposed to heat, certain pHs, and/or moisture during storage. There is, and has been, considerable time, research, and money invested in processes, coatings, capsules, and even packaging technology to try and protect these bacteria from the stressors of manufacture, storage, and gastric transit. Other microorganisms, like spore-forming Bacillus and yeast, are naturally stress-tolerant and therefore easier to keep alive during manufacture and storage.

Lastly, probiotics must “confer a health benefit on the host” when “administered in adequate amounts.” To know what an “adequate amount” is, a microorganismal strain must be tested in a clinical trial.  Without clinical trial data, any assumption around a successful dose is really just speculation. Clinical trials are also necessary to establish what, if any, “benefit on the host” can be conferred by a microorganism.

Prebiotics:

Even though ISAPP published a consensus statement on the definition of a prebiotic in 2017, there is still some debate in the scientific and regulatory communities around what can be considered a prebiotic.

  • The ISAPP definition states that a prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit.
  • Predating the ISAPP consensus, the Food and Agriculture Organization of the United Nations (FAO) defines a prebiotic as a “nonviable food component that confers a health benefit on the host associated with modulation of the microbiota.
  • The FDA has historically cited a different definition as a “non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.

What is the recurring theme? Most of these definitions imply that a prebiotic must be a non-living substance that is undigestible by the intended human or animal consumer and that they must improve host health through selective benefit to certain ‘good’ microorganisms (also known as probiotics) in or on the host.

Non-digestible oligosaccharides (like lactose, or human milk) that can be selectively fermented by ‘good’ bacteria can be considered prebiotics provided they, via clinical trial, have been proven to confer “a health benefit” on the host. But prebiotics do not have to be oligosaccharide or starch based. For example, it has been hypothesized that certain polyphenols, which are abundant in plants, or conjugated fatty acids, which are determined by meat product processing, can also be selectively utilized by certain commensal microbiota.

Importantly, prebiotics do not need to be fermented by ‘good’ microorganisms—aka ‘good’ microorganisms don’t necessarily have to “eat” prebiotics—to selectively benefit them. Polyphenols may also selectively benefit certain ‘good’ microorganisms and moderate the overall gut microbiome by inhibiting specific ‘undesirable’ bacteria. Novel phage-based probiotics can destabilize ‘undesirable’ bacteria thereby releasing the nutrients therein for selective feeding by ‘good’ microorganisms. In doing so, phage-based prebiotics also benefit ‘good’ microorganisms by opening up valuable host real-estate for further colonization.

Synbiotics:

There is also some debate on the definition of synbiotics.

  • ISAPP defines a synbiotic as a “mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.” In practice this generally refers to a combination of probiotics and prebiotics, but according to the ISAPP definition, that doesn’t necessarily have to be the case.  
  • Other more strict definitions in scientific literature include: a “mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and activity of beneficial microorganisms in the gut.”

Synbiotics can be complementary, meaning that their benefit is simply in addition to the probiotic and the prebiotic. This can often be the case when the probiotic in the mixture does not utilize or benefit from the prebiotic in the mixture. Synbiotics can also be synergistic. There is increasing interest in synergistic synbiotics as their benefit is, by definition, greater than the sum of the parts. As with other biotics, the benefit of synbiotics should be demonstrated by clinical trial. 

Postbiotics:

Postbiotics are the newest in popularity and the most convoluted in terms of definition.

According to ISAPP’s recent published definition:

  • A postbiotic is a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.

Based on this definition, a postbiotic must be made of dead microorganisms or a biomass from dead microorganisms, like cell wall components or flagella. These alone or in combination with metabolites produced by these microorganisms before being killed can be considered postbiotics. As with ISAPP’s definition of prebiotics and synbiotics, there is also disagreement on this definition especially since many have historically used the term to describe just metabolites or products of fermentation (like enzymes and short chain fatty acids), not the dead microorganisms themselves. In either case, postbiotics cannot be living and must include a component or product from the once living microorganism. Postbiotics must also confer a health benefit, which as has been stated before, can only be proven via clinical trial.

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