Across the global biotics sector, interest is expanding from live microorganisms toward non‑viable microbial preparations and their derivatives. These so‑called postbiotics are appealing because they tend to be more stable, easier to formulate, and potentially safer for at-risk populations or product formats where live microbes present challenges. Yet the term “postbiotic” remains contested. Earlier literature mainly described postbiotics as microbial metabolites released during fermentation (1, 2) while a more recent consensus statement has broadened the term to include inactivated microbial cells and their components (3). Because of this evolution, the category has become conceptually fragmented, including also ingredients referred to as paraprobiotics, ghost probiotics, metabiotics, lysates, fermentates, and others. This work integrated terms and concepts from all possible definitions from the peer-reviewed literature and real-world products containing postbiotic ingredients, without defining the term “postbiotic”. Here, we will functionally use the word “postbiotics” as an umbrella term for the whole category including all proposed concepts.

In response to this divergence, and the confusion it creates for science, regulation, and commerce, the International Probiotic Association (IPA) led an effort involving industry, academics, and regulatory bodies to develop a practical classification framework (2). The resulting system organizes postbiotic ingredients intended for food and dietary supplements into four technically and commercially meaningful subcategories:

• complex non‑viable microbial preparations (CX)
• intact non‑viable microbial cells (IC)
• fragmented microbial cells (FC)
• microbial metabolic products (MM)

Here, we focus on these four groups, explaining their rationale, characteristics, and implications for manufacturing, safety, and labelling.

Although postbiotic ingredients are already present in global markets, no regulatory jurisdiction has yet established a dedicated framework for them. Instead, regulators evaluate postbiotic ingredients through existing systems designed for foods, dietary supplements, fermentation products, or (in some cases) live microbes. This approach has produced a patchwork landscape. Thailand has authorized several heat‑killed microorganisms as dietary supplement ingredients (4); the United States has received New Dietary Ingredient notifications for certain fermentates (5, 6); Health Canada accepts the term “postbiotic” within its non‑traditional evaluation stream (7); Japan’s Food with Functional Claims (FFC) system accommodates certain postbiotics (8); and the European Union regulates postbiotic ingredients under general food and supplement law without specific category‑level guidance.

These examples illustrate a common challenge: regulators require clarity about what these ingredients are, how they are manufactured, how they are characterized, and how their safety can be reliably assessed. The four‑subcategory system proposed here provides that clarity by distinguishing between ingredients based on their manufacturing process, degree of cellular integrity, and type of bioactive material.

The available scientific literature, although heterogeneous, suggests that postbiotics can be classified into four subcategories (Figure 1).

Figure 1. Decision tree for assigning a non-viable microbial ingredient to postbiotic subcategories intended for foods and dietary supplements. Modified after (2). The workflow applies sequential gates on (Step 1 to 4). OUT indicates that the ingredient is outside the postbiotic field of interest in the proposed framework, because it fails at least one gate (e.g., it contains replicating entities, is not intentionally inactivated, is intended for medicinal purposes, lacks an applicable safety authorization/recognition, or is a purified substance with a completely defined chemical composition). Eligible ingredients are assigned to one of four subcategories: MM (Microbial metabolic products), metabolic products present in unpurified or partially purified culture medium (e.g., cell-free spent culture medium) and including secreted metabolites and biotransformation products; CX (Complex non-viable microbial preparations), unpurified culture medium containing intentionally inactivated microbial cells and/or cell fractions; IC (Intact non-viable microbial cells), intentionally inactivated whole cells separated from the culture medium, with most cells remaining morphologically intact; FC (Fragmented microbial cells), intentionally fragmented cells (e.g., lysates or cell extracts) separated from the culture medium.

Subcategory CX — Complex Non‑Viable Microbial Preparations

CX ingredients are the broadest and most compositionally diverse category. They consist of the entire fermentation broth, culture medium, microbial cells, cell fragments, and microbial metabolites, etc. after intentional inactivation. No separation is performed prior to inactivation, meaning the ingredient reflects the full biological and chemical complexity of the fermentation environment.

Because CX preparations preserve this full mixture, they are often used in products marketed as “ferments” or “fermentates.” A typical example is pasteurized, lyophilized fermented milk containing microbial cells, and their components and metabolites. CX ingredients can be valuable when the combined action of cells, metabolites, and fermentation‑derived compounds contributes to the observed physiological effect.

Manufacturing and characterization of CX ingredients are inherently challenging. Quantification often relies on weight or volume rather than discrete entities, though specific metabolites such as organic acids or exopolysaccharides can serve as standardization markers when evidence supports their relevance. Analytical methods may include gas or liquid chromatography and metabolomic profiling (9). Regulators evaluating CX ingredients generally require detailed knowledge of the fermentation medium and evidence of controlled, reproducible processing, as well as safety documentation for both the progenitor strain and the culture components.

Subcategory IC — Intact Non‑Viable Microbial Cells

IC ingredients consist of whole microbial cells that have been intentionally inactivated and separated from the culture medium. Their morphology must remain intact when viewed microscopically. This category is conceptually the closest to probiotics: the only difference is the absence of viability.

Examples include industrial freeze-dried biomass ingredients from probiotic lactic acid bacteria or bifidobacteria, obtained after centrifugation to remove most of the culture medium and heat-inactivated (pasteurized) at any point in the production process. Because most cells remain whole and structurally defined, this subcategory is generally the simplest to characterize. Enumeration can be performed via flow cytometry, qPCR, digital PCR, or viability‑dye‑assisted PCR (10, 11). Manufacturers may also report input cell numbers by quantifying live cells prior to inactivation.

Regulators are often most comfortable with the IC category because it parallels well‑established probiotic frameworks. If the progenitor strain has an established history of safe use, the transition to a non‑viable format may simplify safety assessment. Indeed, certain jurisdictions such as Australia’s Therapeutic Goods Administration (TGA) have already approved IC‑type postbiotics derived from strains recognized as probiotics.

Subcategory FC — Fragmented Microbial Cells

FC ingredients contain mainly intentionally fragmented cells; lysates, extracts, or mixtures of cell‑wall, membrane, and intracellular components, after removal of most of the culture medium. Unlike IC preparations, FC ingredients do not retain whole cells, and unlike CX ingredients, they do not include the full fermentation broth.

Examples include crude extracts of Saccharomyces cerevisiae or bacterial lysates used in immune‑focused dietary supplements (12, 13). Characterization typically relies on DNA‑based quantification methods (e.g., qPCR or digital PCR) when genomic material remains present (14). Alternatively, manufacturers may standardize the ingredient based on a specific molecular marker such as a membrane‑associated protein, peptidoglycan, or another reproducible structural component (15).

Regulatory assessment of FC ingredients must account for the deliberate fragmentation step. Authorities expect evidence that the process is controlled and reproducible and that the resulting composition remains within defined specifications. Safety considerations include the origin strain, the degree of purification, and the potential presence of allergenic or bioactive components inherent to cellular material.

Subcategory MM — Microbial Metabolic Products

MM ingredients are composed primarily of complex mixtures of microbial metabolites present in cell‑free or partially purified culture medium. These metabolites may include organic acids, exopolysaccharides, vitamins, enzymes, bacteriocins, or compounds produced by microbial biotransformation, such as conversion of daidzin into equol.

A defining feature of MM ingredients is the absence, or near absence, of microbial cells or cell fragments. Consequently, their standardization relies on chemical rather than biological analytical methods. GC‑MS, LC‑MS, and NMR spectroscopy are typical tools for identifying and quantifying metabolites. Some MM ingredients may be standardized to a principal compound considered relevant to the physiological effect. Purified metabolites would, however, be excluded from the category as they can be referred to by their name (e.g. lactic acid).

The regulatory evaluation of MM ingredients resembles that of fermentation‑derived food ingredients more than that of probiotics. Regulators often require full disclosure of fermentation media and expect evidence that the metabolites present do not include harmful by‑products. As with CX preparations, the complexity of MM mixtures demands well‑defined quality specifications and validated analytical methods.

Manufacturing of all postbiotic categories begins with controlled cultivation of the progenitor microorganism. Media components must be food‑grade, and the production environment must follow Good Manufacturing Practices. Comprehensive safety assessment begins with strain‑level identification, typically supported by whole‑genome sequencing to detect potential virulence genes or transferable antimicrobial resistance determinants. Even though the final product is non‑viable, residual DNA can still pose theoretical risks of horizontal gene transfer and must be considered (16).

Intentional inactivation is fundamental. Heat treatment remains the most common method, although high pressure, ultraviolet radiation, and gamma irradiation offer alternatives. The specific choice influences the structural integrity of the cells and consequently the classification into IC, FC, or CX subcategories. Verification of inactivation may require multiple analytical techniques: traditional culture methods, membrane‑integrity stains, or molecular approaches targeting live‑cell markers.

Postbiotics are typically assumed to be more stable than probiotics, but stability is not guaranteed and must be empirically demonstrated. Chemical reactions such as oxidation or hydrolysis can degrade metabolite‑rich preparations, and cell fragments may undergo structural changes that influence functionality. Packaging, moisture control, and temperature management remain critical considerations, even for non‑viable products.

Regardless of subcategory, an ingredient can only be called a postbiotic if it confers a beneficial physiological effect, which covers a broader range of benefits than ‘health benefits’ (such as e.g. non-traditional areas such as sport performance). These effects must be demonstrated directly for the postbiotic preparation itself; benefits cannot be inferred from the live progenitor. Regulatory expectations vary by region, but randomized, placebo‑controlled clinical trials remain the gold standard for substantiating health claims. Because evidence remains scattered across diverse terms, e.g. heat‑inactivated microbes, lysates, fermentates, ongoing efforts to standardize terminology will improve the interpretability of the clinical literature.

The selection of postbiotics versus probiotics should be guided by factors including safety, efficacy, mechanism of action, and compatibility with the product matrix. When both options offer comparable efficacy, practical considerations may ultimately influence the preferred method for achieving the intended physiological outcome (17).

Clear labelling is essential for transparency and consumer trust. Labels should specify the organism of origin at least to the species and, when applicable, strain level, i.e. similar recommendations as for probiotics (18). They should also indicate the postbiotic type (CX, IC, FC, or MM) and provide a meaningful quantitative measure, whether this is a cell count, a mass‑based amount, or a concentration of a defined metabolite. Although postbiotics are ‘dead’, they do not have indefinite shelf-life, storage conditions and expiry date are therefore required. Also serving size, and manufacturer contact information need to be provided. Because postbiotic products are consumed without professional supervision, the terminology must allow consumers to understand what they are ingesting without relying on vague umbrella labels.

The postbiotic category has grown rapidly, but its conceptual and regulatory foundations have lagged behind. The four‑subcategory framework—CX, IC, FC, and MM—offers a coherent structure that reflects manufacturing realities and provides a practical path toward harmonization. Clarifying definitions, stabilizing nomenclature, and establishing consistent characterization practices will support regulatory trust, scientific progress, and responsible product development. Without such alignment, the term “postbiotic” risks remaining ambiguous and vulnerable to misuse. With it, the field can mature into a credible, innovative category within the broader biotics landscape.