Technical Column | The Science and Mechanisms of Postbiotics

BY CHEN CHI-CHEN | ILLUSTRATION BY WANG LING-HUI

Definition of Postbiotics

In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) formally defined postbiotics as: "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host."

The English term "Postbiotics" is derived from Greek roots: the prefix post-, meaning "after," and biotic, meaning "living things" or "life" — together conveying the concept of "after life" or "inanimate." Accordingly, a postbiotic preparation must contain cellular material derived from non-viable microorganisms, which may include: intact inactivated cells; cellular fragments such as cell wall components, membrane lipids, peptidoglycans, teichoic acids, and other macromolecular structures; and/or their accompanying microbial metabolites, such as organic acids, peptides, and enzymes.

The microbial starter strains employed in postbiotic production — whether bacteria or yeasts — must be legally approved in accordance with regulatory positive lists of permissible edible microbial strains for human and/or animal use, and must have undergone safety evaluation at the strain level. Throughout the manufacturing process, these organisms must be subjected to deliberate and controlled inactivation techniques — including, but not limited to, heat treatment, ultraviolet (UV) irradiation, ionizing radiation, high-pressure processing, ultrasonication, or physical/chemical lysis — to permanently terminate their biological viability.

If microbial metabolites generated through fermentation — such as short-chain fatty acids (SCFAs), vitamins, or purified bacteriocins recovered from fermentation broth — undergo extensive purification (e.g., purified butyric acid, purified gamma-aminobutyric acid [GABA]) such that the final preparation contains absolutely no residual cellular biomass or cellular components, these purified chemical entities cannot, per the ISAPP consensus statement, be classified as postbiotics. They should instead be referred to exclusively by their specific chemical names. Postbiotics are not simply "dead bacterial cells." Their capacity to confer meaningful health benefits to the host lies in the unique structural molecules released upon inactivation, which engage in highly specific biochemical interactions with cell membrane receptors or intracellular receptors of the host. 

How Do Postbiotics Work?

Unlike conventional probiotics, postbiotics do not need to "colonize" or "survive" within the gastrointestinal tract. Upon entering the body, they are capable of exerting their biological effects immediately and directly, primarily through the following mechanisms:

Immunomodulation

Although cellular fragments — such as cell wall components — are derived from non-viable microorganisms, their conserved structural features are still recognized by gut-associated immune cells, including dendritic cells and macrophages. This recognition triggers the host's innate defense mechanisms and modulates downstream inflammatory responses.

Barrier Function

Metabolites present in postbiotic preparations — particularly short-chain fatty acids (SCFAs) — serve as a primary energy substrate for intestinal epithelial cells, upregulate the expression of tight junction proteins, and facilitate the repair of intestinal permeability defects. This collectively prevents the translocation of pathogenic bacteria and toxins into the bloodstream, thereby ameliorating a condition commonly referred to as leaky gut syndrome.

Microbiome Modulation

Postbiotics contain naturally occurring antimicrobial compounds — most notably bacteriocins — that directly suppress the growth and proliferation of harmful bacteria, thereby creating a more favorable ecological niche for the survival of resident beneficial microorganisms within the gut.