"20 Postbiotics FAQs" (Part 1) - Summary of Common Questions about Postbiotics

In May 2021, the InternationalProbioticsand Prebiotics Science Association (ISAPP) releasedPostbioticsa consensus statement, officially making postbiotics a highly regarded category in the global gut microbiome field.

What exactly are postbiotics? What are the differences between postbiotics, probiotics, and prebiotics? Why can 'dead bacteria' also be effective? What is the current state of development and regulation in the postbiotics industry?

To help scholars, industry professionals, and consumers gain a deeper and more comprehensive understanding of the research and application development of postbiotics, the Enthusiastic Gut Research Institute has specially written and published "20 Postbiotics FAQs." It addresses 20 hot questions related to postbiotics across the following eight aspects.

1. Definition

01 What are postbiotics?

The International Probiotics and Prebiotics Science Association (ISAPP) defines postbiotics as "preparations of non-living microorganisms and/or their components that confer a health benefit to the host."
According to this definition, effective postbiotics must contain inactivated microbial cells or cell components, which have been proven to have health benefits, regardless of whether they contain bacterial metabolites; they must also meet the following conditions to be considered qualified postbiotic preparations:

A. Clear molecular characteristics of the precursor microorganisms for accurate identification and screening of potential safety-related genes. B. Detailed description of the inactivation process and matrix.

C. Confirmation that the microorganisms have been inactivated.

D. Evidence of health benefits to the host provided by high-quality controlled trials.

E. Detailed description of the components of the postbiotic preparation.

F. Safety assessment of the intended use of the postbiotic preparation in the target host.
 

02 How has the concept of postbiotics evolved?

Various terms have been used in the literature to describe non-living microorganisms that can promote or maintain health, including Postbiotics, Paraprobiotics, Tyndallized probiotics, Non-viable probiotics, Heat-killed probiotics, etc. Currently, Postbiotics is the most commonly used term in the literature.

In 2013, Tsilingiri K et al. proposed that postbiotics refer to factors released by the metabolic activity of probiotics that can have beneficial effects on the host directly or indirectly. In 2018, Aguilar-Toalá et al. redefined postbiotics as soluble factors (products or metabolic by-products) secreted by live bacteria or released after bacterial lysis. In 2019, Aguilar-Toalá further proposed that inactive metabolites produced by probiotics that have biological effects on the host are called postbiotics.

The commonality among the three definitions of postbiotics above is that they do not include microbial cells. Subsequently, different researchers have redefined the concept of postbiotics three times.

Collado M. C. et al. believe that postbiotics refer to compounds produced by microorganisms, released from food components or microbial components, including non-viable cells, which can promote health when the dosage is sufficient. Johnson C. N. argues that non-active products or metabolic by-products produced by beneficial microorganisms that have a positive impact on the host or microbiota can be referred to as postbiotics. Wegh C. A. M. et al. propose that postbiotics refer to functional bioactive substances produced in the substrate during fermentation that can be used to promote health.

Until 2021, ISAPP published a consensus statement on postbiotics in the journal Nature Reviews Gastroenterology and Hepatology, providing the first 'official' concept of postbiotics.

03 What are the differences between the concepts of probiotics, prebiotics, synbiotics, and postbiotics?
Probiotics

Definition: Live microorganisms that confer a health benefit to the host when administered in adequate amounts.

Core: Live microorganisms that are beneficial to health.

Contains live microorganisms: Yes.
Prebiotics

Definition: Substances that are selectively utilized and transformed by the host's microbiota into beneficial compounds for host health.

Core: Food for host microorganisms.

Contains live microorganisms: No.
Synbiotics

Definition: A mixture consisting of live microorganisms and substrates that can be selectively utilized by the host microbiota (including both native and supplemented microorganisms) to confer health benefits to the host.

Core: Complementary synbiotics are a mixture of probiotics and prebiotics; synergistic synbiotics contain live microorganisms and substrates that can be used for their growth.

Contains live microorganisms: Yes.
Postbiotics

Definition: Preparations of non-living microorganisms and/or their components that confer health benefits to the host.

Core: Non-active microorganisms and/or cell components.

Contains live microorganisms: No.
 

04 Do naturally dead microorganisms belong to postbiotics?
Naturally dead microorganisms do not belong to postbiotics.

The ISAPP consensus clearly states that postbiotics are artificially inactivated microbial cells. Naturally dead bacteria are formed after microorganisms undergo normal decay, at which point the microorganisms may have lost their complete structure and efficacy. In contrast, postbiotics are made through specific inactivation methods that render originally active microorganisms inactive and unable to grow and reproduce, while still retaining some degree of microbial structure, characteristics, and efficacy.
 

05 Do purified single metabolites belong to postbiotics?

The ISAPP consensus clearly states that purified microbial metabolites are not postbiotics. Such purified molecules should be named using existing, clear chemical names, such as butyrate or lactate.
 

06 Do complete fermentation liquid metabolites without microbial cells belong to postbiotics?

The ISAPP consensus mentions that effective postbiotics must contain inactivated microbial cells or cell components that are beneficial to the host, while microbial metabolites (supernatants) are not a necessary condition. In other words, according to the ISAPP consensus document, although fermented liquid metabolites have been experimentally verified to be beneficial to the host, they cannot be referred to as postbiotics and should be called acellular supernatants.

However, it is worth noting that 38 scientists, including Zhou Zhigang from the Institute of Feed Research of the Chinese Academy of Agricultural Sciences, specifically wrote to the journal Nature Reviews Gastroenterology and Hepatology regarding the ISAPP consensus, expressing different views on the definition of postbiotics, clearly stating that the original definition of postbiotics refers to substances that have significant benefits for the host, whether singular or mixed.

Therefore, the 'official' concept of postbiotics released by ISAPP may still be subject to revision. Currently, there is no clear definition of postbiotics in regulatory terms in our country. In the future, we may be able to optimize the definition of postbiotics by referring to the definition provided by ISAPP while also considering the scientific research and application of postbiotics.
 

08 Is the commonly found room temperature yogurt on the market considered postbiotic yogurt?

Yogurt is made from fresh milk, inoculated with strains such as Lactobacillus bulgaricus and Streptococcus thermophilus, and fermented under suitable conditions. Commercial room temperature yogurt undergoes pasteurization and other methods after fermentation to kill microorganisms, thus containing a large number of inactivated microorganisms and metabolic products.

Although some lactic acid bacteria have structures and metabolites related to human health, rigorous scientific testing is still needed to prove that the inactive microorganisms (and their metabolites) in yogurt products have health benefits. Currently, most commercially available room temperature yogurts lack relevant research and cannot prove that their components meet the definition of postbiotics.

In addition, there is currently no clear definition of 'postbiotic yogurt', and in fact, in the Chinese market, the definition of 'postbiotics' has not yet been included in any standards or regulations, and further clarification and standardization are urgently needed. Of course, academic research and industrial applications in the field of postbiotics are rapidly developing, and it is believed that the standardization of regulations will follow soon.
 

09 What are the main classifications of postbiotics currently?

Classified by type: whole microbial cells, microbial cell components (cell walls, vesicles, etc.), whole microbial cells and metabolic products, microbial cell components and metabolic products, etc.

Classified by function:Immune regulation, antioxidant, lipid-lowering, blood pressure-lowering, anti-inflammatory, anti-proliferation, etc.

Classified by site of action: oral cavity, intestines, skin, urogenital tract, nasopharynx, etc.
 

09 As a new darling in the raw material industry, what advantages do postbiotics have?

(1) Stability:Maintaining the activity of microorganisms is a challenge, as many probiotics are sensitive to oxygen and heat, but it is easy to obtain products with a long shelf life for non-living microorganisms. Compared to probiotics, postbiotics are more suitable for geographical areas where there are no reliable cold chains or where environmental temperatures cause storage issues for live microorganisms.

(2) Intellectual property:Microorganisms derived from postbiotics cannot be isolated from commercial products, allowing product developers to retain ownership of their components. If the microorganisms producing postbiotics are from countries/regions protected by the Nagoya Protocol, the country of origin will be able to retain management over the microorganisms.

(3) Safety:Since the microorganisms contained in postbiotics have lost their ability to replicate, they will not cause bacteremia or fungemia. However, one cannot infer the safety of postbiotics solely based on the safety of precursor microorganisms; a safety assessment is still needed for any intended use of postbiotics.
……(See you next time)
 

Source: Enthusiastic Intestine Research Institute, authorized for reproduction.