{{Short description|Soluble factors released by bacteria}} {{Multiple issues| {{primary sources|date=November 2019}} {{AI-generated|date=November 2025}} }} '''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.<ref name="Aguilar-Toalá 2018">{{cite journal| vauthors=Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, Mata-Haro V, González-Córdova AF, Vallejo-Cordoba B, Hernández-Mendoza A | title=Postbiotics: An evolving term within the functional foods field | journal=Trends Food Sci Technol | year=2018 | volume=75 | pages=105–14 | doi=10.1016/j.tifs.2018.03.009 }}</ref>
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".<ref name=":0">{{Cite journal |last1=Salminen |first1=Seppo |last2=Collado |first2=Maria Carmen |last3=Endo |first3=Akihito |last4=Hill |first4=Colin |last5=Lebeer |first5=Sarah |last6=Quigley |first6=Eamonn M. M. |last7=Sanders |first7=Mary Ellen |last8=Shamir |first8=Raanan |last9=Swann |first9=Jonathan R. |last10=Szajewska |first10=Hania |last11=Vinderola |first11=Gabriel |date=September 2021 |title=The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics |journal=Nature Reviews Gastroenterology & Hepatology |language=en |volume=18 |issue=9 |pages=649–667 |doi=10.1038/s41575-021-00440-6 |issn=1759-5045 |pmc=8387231 |pmid=33948025}}</ref> 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.<ref name=":0" /> The microbial source should be defined, and the inactivation process and matrix characterized.<ref name=":0" />
== Terminology == Before the ISAPP consensus, related terms such as ''paraprobiotics'' (inactivated or non-viable microbial cells or their crude extracts), ''modified probiotics'',<ref name="Zorzela">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.</ref> ''ghost probiotics'', and ''tyndallized probiotics'' were used in the literature.<ref name=":1">{{Cite journal |last1=Piqué |first1=Núria |last2=Berlanga |first2=Mercedes |last3=Miñana-Galbis |first3=David |date=2019-05-23 |title=Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview |journal=International Journal of Molecular Sciences |language=en |volume=20 |issue=10 |pages=2534 |doi=10.3390/ijms20102534 |doi-access=free |issn=1422-0067 |pmc=6566317 |pmid=31126033}}</ref><ref name=":2">{{Cite journal |last1=Taverniti |first1=Valentina |last2=Guglielmetti |first2=Simone |date=August 2011 |title=The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept) |journal=Genes & Nutrition |language=en |volume=6 |issue=3 |pages=261–274 |doi=10.1007/s12263-011-0218-x |issn=1555-8932 |pmc=3145061 |pmid=21499799}}</ref> When the ISAPP criteria are met, ''postbiotic'' is recommended as the unifying term; paraprobiotics can be considered a subset emphasizing cellular components.<ref name=":0" /><ref name=":1" /><ref name=":2" />
== 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.<ref name=":0" /><ref>{{Citation |last1=Odriozola |first1=A. |last2=González |first2=A. |last3=Odriozola |first3=I. |last4=Álvarez-Herms |first4=J. |last5=Corbi |first5=F. |chapter=Microbiome-based precision nutrition: Prebiotics, probiotics and postbiotics |title=Advances in Host Genetics and microbiome in lifestyle-related phenotypes |date=2024 |series=Advances in Genetics |volume=111 |pages=237–310 |url=https://linkinghub.elsevier.com/retrieve/pii/S0065266024000099 |access-date=2025-09-09 |publisher=Elsevier |language=en |doi=10.1016/bs.adgen.2024.04.001 |pmid=38908901 |isbn=978-0-443-22292-4|url-access=subscription }}</ref>
=== 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.<ref name=":0" /><ref name=":4">{{Cite book |last=Kothari |first=Vijay |title=Probiotics, Prebiotics, Synbiotics, and Postbiotics: Human Microbiome and Human Health |date=2023 |publisher=Springer |others=Prasun Kumar, Subhasree Ray |isbn=978-981-99-1463-0 |edition=1st |location=Singapore}}</ref>
=== 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.<ref>{{Cite book |last=HOSSEIN SAMADI |first=KAFIL; ELHAM |title=POSTBIOTICS SCIENCE, TECHNOLOGY AND APPLICATIONS |date=2021 |publisher=BENTHAM SCIENCE PUBLISHER |isbn=978-1-68108-838-9 |location=S.l.}}</ref>
== Research == Emerging evidence suggest that postbiotics have effects similar to probiotics.<ref name="Berni">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)</ref><ref name="Arai">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.</ref><ref name="Komano">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.</ref>
=== 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.<ref name=":4" /><ref>{{Cite journal |last1=Lin |first1=Wen-Yang |last2=Kuo |first2=Yi-Wei |last3=Chen |first3=Ching-Wei |last4=Huang |first4=Yu-Fen |last5=Hsu |first5=Chen-Hung |last6=Lin |first6=Jia-Hung |last7=Liu |first7=Cheng-Ruei |last8=Chen |first8=Jui-Fen |last9=Hsia |first9=Ko-Chiang |last10=Ho |first10=Hsieh-Hsun |date=September 2021 |title=Viable and Heat-Killed Probiotic Strains Improve Oral Immunity by Elevating the IgA Concentration in the Oral Mucosa |journal=Current Microbiology |language=en |volume=78 |issue=9 |pages=3541–3549 |doi=10.1007/s00284-021-02569-8 |issn=0343-8651 |pmc=8363536 |pmid=34345965}}</ref> Small randomized trials in oral health have reported increased salivary IgA and improvements in oral hygiene outcomes with heat-killed strains or postbiotic lozenges.<ref>{{Cite journal |last1=Lin |first1=Wen-Yang |last2=Kuo |first2=Yi-Wei |last3=Chen |first3=Ching-Wei |last4=Hsu |first4=Yu-Chieh |last5=Huang |first5=Yu-Fen |last6=Hsu |first6=Chen-Hung |last7=Lin |first7=Jia-Hung |last8=Lin |first8=Chi-Huei |last9=Lin |first9=Cheng-Chi |last10=Yi |first10=Tsai-Hsuan |last11=Chu |first11=Yu-Wen |last12=Ho |first12=Hsieh-Hsun |date=2022-09-01 |title=The Function of Mixed Postbiotic PE0401 in Improving Intestinal Health via Elevating Anti-inflammation, Anti-oxidation, Epithelial Tight Junction Gene Expression and Promoting Beneficial Bacteria Growth |url=https://microbiologyjournal.org/the-function-of-mixed-postbiotic-pe0401-in-improving-intestinal-health-via-elevating-anti-inflammation-anti-oxidation-epithelial-tight-junction-gene-expression-and-promoting-beneficial-bacteria-grow/ |journal=Journal of Pure and Applied Microbiology |volume=16 |issue=3 |pages=1771–1782 |doi=10.22207/JPAM.16.3.19|doi-access=free }}</ref><ref>{{Cite journal |last1=Zhang |first1=Chenyue |last2=Wang |first2=Linlin |last3=Liu |first3=Xiaoming |last4=Wang |first4=Gang |last5=Guo |first5=Xinmei |last6=Liu |first6=Xuecong |last7=Zhao |first7=Jianxin |last8=Chen |first8=Wei |date=2023-09-30 |title=The Different Ways Multi-Strain Probiotics with Different Ratios of Bifidobacterium and Lactobacillus Relieve Constipation Induced by Loperamide in Mice |journal=Nutrients |language=en |volume=15 |issue=19 |pages=4230 |doi=10.3390/nu15194230 |doi-access=free |issn=2072-6643 |pmc=10574055 |pmid=37836514}}</ref>
Paraprobiotics/postbiotics have been evalulated for: * Gastrointestinal diseases (bloating, paediatric disorders, infantile colic, diarrhea, extra-intestinal diseases) <ref name="Zorzela" /><ref name="Pique" /> * Upper respiratory tract infections <ref name="Komano" /> * Ocular disorders including eye fatigue<ref name="Morita">Morita, 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).</ref>
=== 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.<ref>{{Cite journal |last1=Guglielmetti |first1=Simone |last2=Boyte |first2=Marie-Eve |last3=Smith |first3=Cathy L. |last4=Ouwehand |first4=Arthur C. |last5=Paraskevakos |first5=George |last6=Younes |first6=Jessica A. |date=2025-09-01 |title=Commercial and regulatory frameworks for postbiotics: an industry-oriented scientific perspective for non-viable microbial ingredients conferring beneficial physiological effects |url=https://www.sciencedirect.com/science/article/pii/S0924224425002663 |journal=Trends in Food Science & Technology |volume=163 |article-number=105130 |doi=10.1016/j.tifs.2025.105130 |issn=0924-2244|hdl=10281/560141 |hdl-access=free }}</ref> Separately, ''in vitro'' work with a mixed postbiotic preparation supports anti-inflammatory, antioxidant, and barrier-supporting activities, along with growth promotion of beneficial bacteria <ref name=":5" />. 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.<ref name=":0" /><ref name="Lee">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).</ref> ''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.<ref name=":5">{{Cite journal |last1=Lin |first1=Chiao-Wen |last2=Chen |first2=Yi-Tzu |last3=Ho |first3=Hsieh-Hsun |last4=Kuo |first4=Yi-Wei |last5=Lin |first5=Wen-Yang |last6=Chen |first6=Jui-Fen |last7=Lin |first7=Jia-Hung |last8=Liu |first8=Cheng-Ruei |last9=Lin |first9=Chi-Huei |last10=Yeh |first10=Yao-Tsung |last11=Chen |first11=Ching-Wei |last12=Huang |first12=Yu-Fen |last13=Hsu |first13=Chen-Hung |last14=Hsieh |first14=Pei-Shan |last15=Yang |first15=Shun-Fa |date=2022-03-15 |title=Impact of the food grade heat-killed probiotic and postbiotic oral lozenges in oral hygiene |journal=Aging |language=en |volume=14 |issue=5 |pages=2221–2238 |doi=10.18632/aging.203923 |issn=1945-4589 |pmc=8954981 |pmid=35236778}}</ref><ref name="Jang">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.</ref>
== Safety and regulation == Because postbiotics are non-viable, they avoid risks related to microbial translocation or infection associated with live microbes.<ref name="Pique">Pique, N., M. Berlanga, and D. Minana-Galbis, Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci, 2019. 20(10).</ref> Nonetheless, safety should be evaluated case-by-case (e.g., endotoxin levels, processing residuals, immunological responses).<ref name=":0"/> 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'' <ref name="Sang2015"/><ref name="Sang2013"/> ** ''Bifidobacterium infantis'' <ref name="Sang2015">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.</ref><ref name="Sang2013">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.</ref> ** ''Bifidobacterium longum'' <ref name="Sang2015"/><ref name="Sang2013"/> * Lactobacillales ** ''Enterococcus faecalis'' <ref name="Chung">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).</ref><ref name=Choi2017/> ** Lactobacillaceae *** ''Lactobacillus'' **** ''Lactobacillus acidophilus'' <ref name="Sang2015"/><ref name="Sang2013"/> ***** ''L. acidophilus'' fermentation product is approved as an over-the-counter drug in China under the name {{lang|zh|乳酸菌素}} (official English name: lacidophilin).<ref>{{cite web |title=乳酸菌素片说明书 |url=https://www.nmpa.gov.cn/wwwroot/otc2h/x071.htm|trans-title=Lacidophilin tablet, package insert|work=Second Batch of the National Non-prescription Chemical Drug Package Insert Catalog|author1=National Medical Products Administration}}</ref> It was invented in 1978.<ref name=cg>{{cite web|url=https://www.chinagut.cn/articles/ss/ba8b3cd0419e482c86124252a61ced99|title=走过四十五载，乳酸菌素蓄势启航|website=chinagut.cn|date=2023-11-09}}</ref> **** ''Lactobacillus bulgaricus'' <ref name="Sang2015"/><ref name="Sang2013"/><ref name="Warda">Warda, A.K., et al., Heat-killed lactobacilli alter both microbiota composition and behaviour. Behav Brain Res, 2019. 362: pp. 213–23.</ref> **** ''Lactobacillus johnsonii'' <ref name="Chuang">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).</ref> **** ''Lactococcus lactis''<ref name="Komano"/> *** ''Lacticaseibacillus casei''<ref name="Sang2015"/><ref name="Sang2013"/><ref name=Saito2018>Saito, 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.</ref> *** ''Lacticaseibacillus paracasei'' <ref name="Berni"/><ref name="Arai"/> *** ''Lactiplantibacillus plantarum'' <ref name="Lee"/><ref name="Jang"/><ref name="Liu">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.</ref><ref name="Sang2015"/><ref name="Sang2013"/><ref name="Park">Park, S., et al., Effects of heat-killed Lactobacillus plantarum against influenza viruses in mice. J Microbiol, 2018. 56(2): pp. 145–49.</ref> *** ''Levilactobacillus brevis''<ref name="Choi2017">Choi, 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.</ref><ref name="Saito2019">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.</ref> *** ''Limosilactobacillus reuteri''<ref name="Liao">Liao, 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.</ref><ref name=Ting>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.</ref> *** ''Limosilactobacillus fermentum'' <ref name="Warda"/> *** ''Ligilactobacillus salivarius'' <ref name="Chuang"/> ** ''Streptococcus salivarius'' subsp. ''thermophilus''<ref name="Sang2015"/><ref name="Sang2013"/><ref name="Gao">Gao, X., et al., Effect of heat-killed Streptococcus thermophilus on type 2 diabetes rats. PeerJ, 2019. 7: p. e7117.</ref>
== References == <!--- See http://en.wikipedia.org/wiki/Wikipedia:Footnotes on how to create references using<ref></ref> tags, these references will then appear here automatically --> {{reflist}}
<!--- Categories ---> Category:Probiotics Category:Bacteriology Category:Digestive system Category:Food microbiology Category:Nutrition Category:Gut flora