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Behind the publication: Understanding ISAPP’s new scientific consensus definition of postbiotics

A key characteristic of a probiotic is that it remains alive at the time of consumption. Yet scientists have known for decades that some non-living microorganisms can also have benefits for health: various studies (reviewed in Ouwehand & Salminen, 1998) have compared the health effects of viable and non-viable bacteria, and some recent investigations have tested the health benefits of pasteurized bacteria (Depommier et al., 2019).

Since non-viable microorganisms are often more stable and convenient to include in consumer products, interest in these ‘postbiotic’ ingredients has increased over the past several years. But before now, the scientific community had not yet united around a definition, nor had it precisely delineated what falls into this category.

An international group of scientists from the disciplines of probiotics and postbiotics, food technology, adult and pediatric gastroenterology, pediatrics, metabolomics, regulatory affairs, microbiology, functional genomics, cellular physiology and immunology met in 2019 to discuss the concept of postbiotics. This meeting led to a recently published consensus paper, including this definition: “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.

Thus, a postbiotic must include some non-living microbial biomass, whether it be whole microbial cells or cell components.

Below is a Q&A with four of the paper’s seven ISAPP-linked authors, who highlight important points about the definition and explain how it will lay the groundwork for better scientific understanding of non-viable microbes and health in the years ahead.

Why was the concept of postbiotics needed?

Prof. Seppo Salminen, University of Turku, Finland:

We have known for a long time that inactivated microorganisms, not just live ones, may have health effects but the field had not coalesced around a term to use to describe such products or the key criteria applicable to them. So we felt we needed to assemble key experts in the field and provide clear definitions and criteria.

Further, novel microbes (that is, new species hitherto not used in foods) in foods and feeds are being introduced as live or dead preparations. The paper highlights regulatory challenges and for safety and health effect assessment for dead preparations of microbes.

Can bacterial metabolites be postbiotics?

Prof. Gabriel Vinderola, National University of Litoral, Argentina:

Postbiotics can include metabolites – for example, fermented products with metabolites and microbial cells or their components, but pure metabolites are not postbiotics.

Can you expand on what is not included in the category of postbiotics?

Dr. Mary Ellen Sanders, ISAPP Executive Science Officer, USA:

The term ‘postbiotic’ today is sometimes applied to components derived from microbial growth that are purified, so no cell or cell products remain. The panel made the decision that such purified, microbe-derived substances (e.g. butyrate) should be called by their chemical names and that there was no need for a single encompassing term for them. Some people may be surprised by this. But microbe-derived substances include a whole host of purified pharmaceuticals and industrial chemicals, and these are not appropriately within the scope of ‘postbiotics’.

For something to be a postbiotic, what kinds of microorganisms can it originate from?

Prof. Gabriel Vinderola, National University of Litoral, Argentina:

A postbiotic must derive from a living microorganism on which a technological process is applied for life termination (heat, high pressure, oxygen exposure for strict anaerobes, etc). Viruses, including bacteriophages, are not considered living microorganisms, so postbiotics cannot be derived from them.

Safety and benefits must be demonstrated for its non-viable form. A postbiotic does not have to be derived from a probiotic (see here for a list of criteria required for a probiotic). So the microbe used to derive a postbiotic does not need to demonstrate a health benefit while alive. Further, a probiotic product that loses cell viability during storage does not automatically qualify as a postbiotic; studies on the health benefit of the inactivated probiotic are still required.

Vaccines or substantially purified components and products (for example, proteins, peptides, exopolysaccharides, SCFAs, filtrates without cell components and chemically synthesized compounds) would not qualify as postbiotics in their own right, although some might be present in postbiotic preparations.

What was the most challenging part of creating this definition?

Dr. Mary Ellen Sanders, ISAPP Executive Science Officer, USA:

The panel didn’t want to use the term ‘inactive’ to describe a postbiotic, because clearly even though they are dead, they retain biological activity. There was a lot of discussion about the word ‘inanimate’, as it’s not so easy to translate. But the panel eventually decided it was the best option.

 Does this definition encompass all postbiotic products, no matter whether they are taken as dietary supplements or drugs?

Prof. Hania Szajewska, Medical University of Warsaw, Poland:

Indeed. However, as of today, postbiotics are found primarily in foods and dietary supplements.

Where can you currently find postbiotics in consumer products, and what are their health effects?

Prof. Hania Szajewska, Medical University of Warsaw, Poland:

One example is specific fermented infant formulas with postbiotics which have been commercially available in some countries such as Japan and in Europe, South America, and the Middle East for years. The postbiotics in fermented formulas are generally derived from fermentation of a milk matrix by Bifidobacterium, Streptococcus, and/or Lactobacillus strains.

Potential clinical effects of postbiotics include prevention of common infectious diseases such as upper respiratory tract infections and acute gastroenteritis. Moreover, fermented formulas have the potential to improve some digestive symptoms or discomfort (e.g. colic in infants). In addition, there is some rationale for immunomodulating, anti-inflammatory effects which may potentially translate into other clinical benefits, such as improving allergy symptoms. Still, while these effects are likely, more well-designed, carefully conducted trials are needed.

What do we know about postbiotic safety?

Dr. Mary Ellen Sanders, ISAPP Executive Science Officer, USA:

Living microbes have the potential, especially in people with compromised health, to cause an infection. But because the microbes in postbiotics are not alive, they cannot cause infections. This risk factor, then, is removed from these preparations. Of course, the safety of postbiotics for their intended use must be demonstrated, but infectivity should not be a concern.

What are the take-home points about the postbiotics definition?

Prof. Seppo Salminen, University of Turku, Finland:

Postbiotics, which encompass inanimate microbes with or without metabolites, can be characterized, are likely to be more stable than live counterparts and are less likely to be a safety concern, since dead bacteria and yeast are not infective.

Read the postbiotic definition paper here.

See the press release about this paper here.

View an infographic on the postbiotic definition here.

New publication co-authored by ISAPP board members gives an overview of probiotics, prebiotics, synbiotics, and postbiotics in infant formula

For meeting the nutritional needs of infants and supporting early development, human milk is the ideal food—and this is reflected in breastfeeding guidelines around the world, including the World Health Organization’s recommendation that babies receive human milk exclusively for the first six months of life and that breastfeeding be continued, along with complementary foods, up to two years of age or beyond. In certain cases, however, breastfeeding is challenging or may not even be an option. Then, parents rely on alternatives for feeding their infants.

A group of scientists, including three ISAPP board members, recently co-authored an article in the journal Nutrients entitled Infant Formula Supplemented with Biotics: Current Knowledge and Future Perspectives. In the review, they aimed to highlight the new technologies and ingredients that are allowing infant formula to better approximate the composition of human milk. They focused on four types of ingredients: probiotics, prebiotics, synbiotics, and postbiotics.

Co-author Gabriel Vinderola, Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL) in Santa Fe, Argentina says, “Modern technologies have allowed the production of specific microbes, subtrates selectively used by the host microbes, and even non-viable microbes and their metabolites and cell fragments—for which scientific evidence is available on their effects on infant health, when administered in adequate amounts. Thus, this current set of gut modulators can be delivered by infant formula when breastfeeding is limited or when it is not an option.”

The authors say a well-functioning gut microbiota is essential for the overall health and proper development of the infant, and components of human milk support the development of this microbiota. They list important human milk components and the novel ingredients that aim to mimic the functions of these components in infant formulas:

  • Human milk oligosaccharides (HMOs)

HMOs are specialized complex carbohydrates found in human milk, which are digested in the infant colon and serve as substrates for beneficial microbes, mainly bifidobacteria, residing there. In recent years, prebiotic mixtures of oligosaccharides (e.g. short-chain GOS and long-chain FOS) have been added to infant formula to recapitulate the effects of HMOs. But now that it’s possible to produce several types of HMOs synthetically, some infant formulas are enriched with purified HMOs: 2’-fucosyllactose (2’FL) or lacto-N-neotetraose (LNnT). Even 3′-galactosyllactose (3′-GL) can be naturally produced by a fermentation process in certain infant formulas.

  • Human milk microbiota

Human milk has a complex microbiota, which is an important source of beneficial bacteria to the infant. Studies support the notion that the human milk microbiota delivers bioactive components that support the development of the infant’s immune system. Probiotic strains are sometimes added to infant formula in order to substitute for important members of the milk microbiota.

  • Bacterial metabolites

Human milk also contains metabolic byproducts of bacteria called “metabolites” in addition to the bacteria themselves. These components have not been fully studied to date, but bacterial metabolites such as butyrate and other short-chain fatty acids may have important health effects for the overall development of the infant. A future area of nutritional research is likely to be the addition of ‘postbiotics’ — non-viable cells, their metabolites and cell components that, when administered in adequate amounts, promote health and well-being — to infant formulas. (ISAPP convened a scientific consensus panel on the definition of postbiotics, with publication of this definition expected by the end of 2020.)

 

The precise short- and long-term health benefits of adding the above ingredients to infant formula are still under study. One pediatric society (the ESPGHAN Committee on Nutrition) examined the data in 2011 and at that time did not recommend the routine use of infant formulas with added probiotic and/or prebiotic components until further trials were conducted. A systematic review concluded that evidence for the health benefits of fermented infant formula (compared with standard infant formula) are unclear, although improvements in infant gastrointestinal symptoms cannot be ruled out. Although infant formulas are undoubtedly improving, review co-author Hania Szajewska, MD, Professor of Paediatrics at The Medical University of Warsaw, Poland, says, “Matching human milk is challenging. Any alternative should not only match human milk composition, but should also match breastfeeding performance, including how it affects infant growth rate and other functions, such as the immune response.”