Postbiotics are preparations of dead microorganisms and/or their components that are believed to confer a health benefit on the host. Most such preparations are derived from bacteria believed to be beneficial (so-called probiotics), with most purported benefits having to do with the digestive tract.
In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) issued a consensus definition that helped align terminology across research and applications. The definition states that a postbiotic is "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Under this consensus, postbiotics include inactivated microbial cells or cell components, with or without co-present metabolites, but exclude substantially purified metabolites alone, vaccines, filtrates devoid of cell components, and purely synthetic compounds. The microbial source should be defined, and the inactivation process and matrix characterized.
Terminology Before the ISAPP consensus, related terms such as paraprobiotics (inactivated or non-viable microbial cells or their crude extracts), modified probiotics,Zorzela, L., et al., Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature. Benef Microbes, 2017. 8(5): pp. 739–54. ghost probiotics, and tyndallized probiotics were used in the literature. When the ISAPP criteria are met, postbiotic is recommended as the unifying term; paraprobiotics can be considered a subset emphasizing cellular components.
Preparation Postbiotics are obtained by deliberate inactivation of well-characterized microorganisms. In manufacturing for foods and supplements, physical inactivation methods are preferred to ensure safety and avoid chemical residues. Common approaches to killing include thermal processing (e.g., pasteurization, tyndallization) and non-thermal methods such as high-pressure processing, irradiation, and sonication.
Composition Preparations may contain cell wall fragments (e.g., peptidoglycan, teichoic acids), surface proteins (e.g., S-layer proteins, pili), exopolysaccharides, and metabolites present in the matrix. Transparent reporting of the starting strain(s), inactivation method, and matrix is recommended.
Classification
IPA framework The International Probiotics Association (IPA) proposed an industry-oriented decision tree and four subcategories for non-viable microbial ingredients used in foods/dietary supplements: CX (complex non-viable microbial preparations) unpurified culture medium containing intentionally inactivated cells and/or cell fractions IC (intact non-viable microbial cells) intentionally inactivated whole cells separated from the culture medium FC (fragmented microbial cells) intentionally fragmented cells (e.g., lysates/extracts) separated from the culture medium MM (microbial metabolic products) metabolic products in unpurified or partially purified culture medium. Nature-identical synthetic components and single purified molecules are excluded and microbial origin is required. This framework aims to harmonize nomenclature, standardization and labeling in commercial contexts, and its scope may not fully align with all academic definitions.
Research Emerging evidence suggest that postbiotics have effects similar to probiotics.Berni Canani, R., et al., Specific Signatures of the Gut Microbiota and Increased Levels of Butyrate in Children Treated with Fermented Cow's Milk Containing Heat-Killed Lactobacillus paracasei CBA L74. Appl Environ Microbiol, 2017. 83(19)Arai, S., et al., Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice. PLoS One, 2018. 13(6): p. e0199018.Komano, Y., et al., Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial. J Int Soc Sports Nutr, 2018. 15(1): p. 39.
Clinical research
Evidence is emerging across pediatric and adult populations, with reviews summarizing potential roles in gastrointestinal health (e.g., symptom management in functional bowel disorders), immune support (e.g., reducing common infections), and other areas. Small randomized trials in oral health have reported increased salivary IgA and improvements in oral hygiene outcomes with heat-killed strains or postbiotic lozenges.
Paraprobiotics/postbiotics have been evalulated for: Gastrointestinal diseases (bloating, paediatric disorders, infantile colic, diarrhea, extra-intestinal diseases) Upper respiratory tract infections Ocular disorders including eye fatigueMorita, Y., et al., Effect of Heat-Killed Lactobacillus paracasei KW3110 Ingestion on Ocular Disorders Caused by Visual Display Terminal (VDT) Loads: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study. Nutrients, 2018. 10(8).
Preclinical research
In mouse models of loperamide-induced constipation, multi-strain probiotic formulations with a defined postbiotic added relieved constipation-related endpoints and were associated with shifts in gut microbiota composition, gastrointestinal regulatory transmitters, inflammatory cytokines, and fecal short-chain fatty acids. Separately, in vitro work with a mixed postbiotic preparation supports anti-inflammatory, antioxidant, and barrier-supporting activities, along with growth promotion of beneficial bacteria . These findings warrant confirmation in well-designed human studies.
There is a body of pre-clinical evidence suggesting the use of paraprobiotics in: Colitis-associated colorectal cancer Type 2 Diabetes (improved glycemic parameters) Liver injury Atopic dermatitis Influenza viruses Cardiac injury
Proposed mechanisms Proposed mechanisms include modulation of mucosal immune responses via microbe-associated molecular patterns interacting with host pattern-recognition receptors; support of epithelial barrier function (e.g., tight-junction signaling); antagonism against microbes via bacteriocins or organic acids; and systemic signaling influencing metabolic pathways.Lee, A., et al., Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity. Nutrients, 2017. 9(6). In vitro findings with a mixed postbiotic preparation have reported anti-inflammatory and antioxidant effects, increased expression of epithelial tight-junction genes, and promotion of beneficial bacteria.Jang, H.J., et al., Antioxidant effects of live and heat-killed probiotic Lactobacillus plantarum Ln1 isolated from kimchi. J Food Sci Technol, 2018. 55(8): pp. 3174–80.
Safety and regulation Because postbiotics are non-viable, they avoid risks related to microbial translocation or infection associated with live microbes.Pique, N., M. Berlanga, and D. Minana-Galbis, Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci, 2019. 20(10). Nonetheless, safety should be evaluated case-by-case (e.g., endotoxin levels, processing residuals, immunological responses). Postbiotics are not a distinct regulatory category; products are typically evaluated under existing frameworks (e.g., foods, dietary ingredients, or medicines) [1, 4].
Commonly used taxa Bifidobacteriales Bifidobacterium Bifidobacterium breve Bifidobacterium infantis Sang, L.X., et al., Live and heat-killed probiotic: effects on chronic experimental colitis induced by dextran sulfate sodium (DSS) in rats. Int J Clin Exp Med, 2015. 8(11): pp. 20072–78.Sang, L.X., et al., Heat-killed VSL#3 ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in rats. Int J Mol Sci, 2013. 15(1): pp. 15–28. Bifidobacterium longum Lactobacillales Enterococcus faecalis Chung, I.C., et al., Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice. Nutrients, 2019. 11(3). Lactobacillaceae Lactobacillus Lactobacillus acidophilus L. acidophilus fermentation product is approved as an over-the-counter drug in China under the name (official English name: lacidophilin). It was invented in 1978. Lactobacillus bulgaricus Warda, A.K., et al., Heat-killed lactobacilli alter both microbiota composition and behaviour. Behav Brain Res, 2019. 362: pp. 213–23. Lactobacillus johnsonii Chuang, C.H., et al., Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo. Molecules, 2016. 21(11). Lactococcus lactis Lacticaseibacillus caseiSaito, Y., et al., Effects of heat-killed Lactobacillus casei subsp. casei 327 intake on defecation in healthy volunteers: a randomized, double-blind, placebo-controlled, parallel-group study. Biosci Microbiota Food Health, 2018. 37(3): pp. 59–65. Lacticaseibacillus paracasei Lactiplantibacillus plantarum Liu, Y.W., et al., Oral administration of heat-inactivated Lactobacillus plantarum K37 modulated airway hyperresponsiveness in ovalbumin-sensitized BALB/c mice. PLoS One, 2014. 9(6): p. e100105.Park, S., et al., Effects of heat-killed Lactobacillus plantarum against influenza viruses in mice. J Microbiol, 2018. 56(2): pp. 145–49. Levilactobacillus brevisChoi, C.Y., et al., Anti-inflammatory potential of a heat-killed Lactobacillus strain isolated from Kimchi on house dust mite-induced atopic dermatitis in NC/Nga mice. J Appl Microbiol, 2017. 123(2): pp. 535–43.Saito, H., et al., Oral administration of heat-killed Lactobacillus brevis SBC8803 elevates the ratio of acyl/des-acyl ghrelin in blood and increases short-term food intake. Benef Microbes, 2019: pp. 1–8. Limosilactobacillus reuteriLiao, P.H., et al., Heat-killed Lactobacillus Reuteri GMNL-263 Prevents Epididymal Fat Accumulation and Cardiac Injury in High-Calorie Diet-Fed Rats. Int J Med Sci, 2016. 13(8): pp. 569–77.Ting, W.J., et al., Heat Killed Lactobacillus reuteri GMNL-263 Reduces Fibrosis Effects on the Liver and Heart in High Fat Diet-Hamsters via TGF-beta Suppression. Int J Mol Sci, 2015. 16(10): pp. 25881–96. Limosilactobacillus fermentum Ligilactobacillus salivarius Streptococcus salivarius subsp. thermophilusGao, X., et al., Effect of heat-killed Streptococcus thermophilus on type 2 diabetes rats. PeerJ, 2019. 7: p. e7117.
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