Current strategies for altering the human gut microbiome include diet (i.e., prebiotics and some fermented foods) and live biotherapeutics. The latter strategy includes undefined fecal microbiota transplants and defined microbial consortia (targeted formulations from simple microbial consortia, or probiotics, to consortia of 50 or more bacterial taxa and strains used to shape host microbiota).

Some non-living microorganisms, collectively defined as postbiotics, are also being explored as a means of reducing the risk of disease and improving health.

Although this is not the case for all bacteria and health benefits, non-viable bacteria often have been shown to have similar effectiveness as viable bacteria counterparts. With the added longer shelf-life and easier storage that favors both the technology and stability, there is now increased interest in these bacteria being included in consumer products. For instance, in 2019 Patrice D. Cani and colleagues showed that metabolic outcomes in individuals who are overweight and obese when treated with pasteurized Akkermansia muciniphila were more consistent compared to individuals who received live A. muciniphila.

Until now, however, scientists have yet to agree on a definition of what is a postbiotic.

A recently published consensus paper by scientists worldwide working in different disciplines now defines a postbiotic as “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.

As such, the components of a postbiotic include intact inanimate microbial cells and/or microbial cell fragments or structures with or without metabolites.

While the new definition of postbiotics can include metabolites, if accompanied by non-living microbial biomass (e.g., fermented foods with bacterial metabolites and microbial cells), neither filtrates without cell components, purified microbial components or metabolites nor vaccines are classed as postbiotics. Thus, from now on, purified microbe-derived substances (e.g., butyrate) should be called by their specific chemical name and are not considered postbiotics.

In addition to providing a clear definition of a postbiotic, the consensus paper also highlights regulatory challenges and criteria that should be used for assessing the safety and health effects of preparations of dead microbes.

A postbiotic must derive from a living microorganism to which a technological process (e.g., pasteurization) is applied that means the microbe cannot replicate. In order to preserve overall quality and nutritional value while maintaining sensory characteristics, other non-thermal procedures such as drying techniques and high pressure are also used, even though it is important that the functional properties of the postbiotic are not affected by the treatment. As viruses are not considered live microorganisms, postbiotics cannot be derived from them. Furthermore, the microbe used to derive a postbiotic does not need to show a health benefit, as a postbiotic does not have to be derived from a probiotic.

The new definition of postbiotics states that these products can be taken as foods, dietary supplements or drugs. For instance, postbiotics can be found in yogurt and specific fermented infant formulas. In addition, the site of action for postbiotics include the gut or any host surface, such as the skin, oral cavity or urogenital tract.

We now require studies on the health benefit and safety of the postbiotic preparation in terms of the intended use in the target host, which includes humans, companion animals and livestock.

Potential clinical effects of postbiotics include eradicating Helicobacter pylori infection, preventing common infectious diseases (e.g., upper respiratory tract infections and acute gastroenteritis), alleviating symptoms associated with irritable bowel syndrome and abrogating the negative effects of stress. The underlying mechanisms behind the health benefits of postbiotics include modulating the host microbiota, enhancing epithelial barrier functions, modulating local and systemic immune responses, modulating metabolic responses and systemic signaling via the nervous system.

As for their safety, as the microbes in postbiotics are not alive, they cannot cause infections. This offers potential for use in compromised individuals, for whom live biotherapeutics are not recommended.

On the whole, postbiotics include inanimate microbes with or without metabolites that have been shown to have health benefits and are likely to be safer and more stable than live counterparts. As in the case of probiotics and prebiotics, clinical trials in different populations are needed before their systematic use is recommended.

 

References:

Ouwehand AC, Salminen SJ. The health effects of cultured milk products with viable and non-viable bacteria. Int Dairy J. 1998; 8(9):749-758. doi: 10.1016/S0958-6946(98)00114-9.

Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021. doi: 10.1038/s41575-021-00440-6.

Hill C. Balancing the risks and rewards of live biotherapeutics. Nat Rev Gastroenterol Hepatol. 2020; 17(3):133-134. doi: 10.1038/s41575-019-0254-3.