Postbiotics: Inactivated Microbes and Their Products

Table of Contents

1. The 2021 Consensus Definition
2. How Postbiotics Differ from the Other “-Biotics”
3. What Counts and What Does Not
4. Inactivated Microbes in Everyday Fermented Foods
5. How Dead Microbes Are Thought to Act
6. Human Trials: Irritable Bowel Syndrome and the Gut
7. Human Trials: Infant Formula and Childhood Infections
8. Human Trials: Colds, Skin and Metabolism in Adults
9. Claimed Advantages and the Safety Findings
10. What Is Not Known
11. Key Research Papers
12. Connections
13. Featured Videos

The 2021 Consensus Definition

In 2019 the International Scientific Association for Probiotics and Prebiotics brought together experts in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to settle a term that, in the panel’s words, was “increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition.” Their consensus statement, first-authored by Salminen and published in 2021, defines a postbiotic as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.” The same abstract adds that effective postbiotics “must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits.”

Each word in the definition was argued over, and the full text of the statement explains the choices:

• “Inanimate” was chosen, meaning lifeless, rather than “inactive”, because “inactive” suggests an inert material. The panel wanted a word that says the microbes were once alive and have been killed, without implying they no longer do anything.
• “Preparation” was chosen because the particular microbe, the material it was grown in and the way it was killed may all shape any effect. A postbiotic is a specific, described preparation, not a microbe species in general.
• “Components” was included because whole cells may not be needed: effects might come from pili, cell-wall pieces or other structures.
• “Confers a health benefit” means that, as with probiotics, a material does not earn the name until a benefit has been shown in the target host — the species and the group of people it is meant for.

The panel’s summary points add that a postbiotic does not have to come from a probiotic strain; that it has to be applied at a body surface (mouth, gut, skin, urogenital tract or nasopharynx) and that injections fall outside the term; and that the microbes have to be “deliberately inactivated.” A 2022 review by four of the panel members notes that older terms — paraprobiotics, ghostbiotics, heat-inactivated probiotics, non-viable probiotics, cell fragments and cell lysates — all fit inside the term as defined. A 2023 perspective adds that the definition “does not stipulate any specific health benefit, finished product, target population or regulatory status.”

The Probiotics: History and Discovery page already quotes this definition in its account of the 2021 panels; this page picks up where that account stops.

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How Postbiotics Differ from the Other “-Biotics”

The International Scientific Association for Probiotics and Prebiotics has now issued consensus definitions for five related terms. Set side by side, the difference is mostly about whether anything in the product is alive, and what it is meant to do in the body.

Two points in that table are easy to miss. First, the synbiotic definition changed in 2020. The Probiotics page describes a synbiotic as a probiotic combined with a prebiotic; the 2020 panel kept that as one kind (a “complementary” synbiotic, in which each part has to meet its own definition) and added a “synergistic” kind, in which the fibre or other substrate is chosen to be used by the microbe it is packaged with. Second, the fermented-food definition says nothing about live microbes at all. The 2021 fermented-food panel spelled out how fermented foods differ from probiotics, and the postbiotic panel added that a fermented food is not automatically a postbiotic either (see the next two sections).

The postbiotics statement also points out an overlap. Probiotics have to contain enough living cells when taken, but the panel writes that most probiotic preparations, “especially at the end of shelf life,” also hold “potentially large numbers of dead and injured microorganisms,” and that what those dead cells do has had little attention.

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What Counts and What Does Not

The consensus is specific about the edges of the term. The following is taken from the full text of the 2021 statement.

Included

• Whole killed cells of bacteria or yeasts, for example heat-killed lactobacilli or bifidobacteria.
• Cell fragments and lysates — pieces of cell wall, pili and other structures — provided the preparation meets the other criteria. Bacterial lysates were left out of the panel’s literature count but, the text says, “may be considered postbiotics if health benefits are documented.”
• Metabolites carried along with the cells. Lactic acid, short-chain fatty acids such as butyrate, and peptides made during growth or fermentation may be present in a postbiotic preparation, as long as the cellular material is there too.

Excluded

• Purified metabolites on their own. The definition “would not include substantially purified metabolites in the absence of cellular biomass.” The panel writes that such molecules are better named by their chemical names, “for example, butyric acid or lactic acid.” So a purified short-chain fatty acid, a purified exopolysaccharide, a protein or peptide, or a filtrate with the cells removed is not a postbiotic in its own right. This is the main point of difference with several earlier definitions, which the panel lists in a table and which described postbiotics as metabolites or soluble factors only.
• Vaccines, chemically synthesised compounds, and viruses, including bacteriophages.
• Preparations from undefined microbes. The microbes have to be characterised before they are killed. The panel gives the example that “many traditional fermented foods are made through the action of undefined, mixed cultures, and such a product could not be used for the preparation of a postbiotic.” Products made with defined starter cultures could be.
• Anything given by injection.

The statement lists six criteria a preparation has to meet: molecular identification of the starting microbes (for example a fully annotated genome) with a screen for genes of safety concern; a description of the inactivation method and the growth material; confirmation that inactivation actually happened; evidence of a health benefit in the host “from a controlled, high-quality trial”; a description of the preparation’s make-up; and a safety assessment in the target host for the intended use.

The 2022 review by Vinderola and colleagues sums up the effect of these choices: the definition centres on the “progenitor microbial cell or cell fragments, not just metabolites, proteins or carbohydrates they might produce,” and those microbe-made products “are not required to be present.”

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Inactivated Microbes in Everyday Fermented Foods

Long before the word existed, people ate dead fermentation microbes every day. The postbiotics consensus says so directly: fermented foods “might also contain a substantial number of non-viable microbial cells, particularly after prolonged storage or after processing, such as pasteurization (for example, soy sauce) or baking (for example, sourdough bread).”

The 2021 fermented-foods consensus, first-authored by Marco, sorts common foods by whether live microbes are usually present when they are eaten. Its table (full text) places these foods on each side:

The same statement explains why bread sits in the second column: leavened breads “are baked after fermentation, effectively killing the fermentation microorganisms.” It proposes that pasteurised fermented foods without live microbes be labelled “foods made by fermentation” rather than as containing live cultures. Sourdough fermentation is also credited in that statement with breaking down phytate, which, it says, improves calcium, magnesium, iron and zinc uptake from these breads.

For the fermented soy foods, two points come from the sources. Miso, natto and tempeh are listed among foods that usually carry live microbes as made. And the postbiotics consensus describes Japan as a country where products made with killed lactic acid bacteria or bifidobacteria — which the researcher Mitsuoka called “biogenics” in 1998 — have been sold “for more than 100 years,” with natto and instant-type miso soup among the foods to which they are added. Most of those products carry no health claim, and the panel notes that their labels do not always say the added microbes are dead. How much heat a home cook’s miso soup or cooked natto takes, and how many cells survive, is not measured in these sources; the site’s Natto, Bacillus subtilis and Gut Health page notes that natto’s spores tolerate heat far better than active cells.

One caution follows from the definitions. A loaf of sourdough bread or a pasteurised pickle contains inanimate microbes, but under the 2021 consensus it is not “a postbiotic”: most such foods are made with undefined mixed cultures, and no health benefit has been shown for that specific preparation in a controlled trial. They are fermented foods that happen to carry dead microbes.

A small Norwegian pilot trial shows why the dead fraction is of interest. Thirty-four people with irritable bowel syndrome added either pasteurised (15 people) or unpasteurised (19 people) sauerkraut to their diet for 6 weeks. Symptom scores fell in both groups (a mean change of −38.57 points on the pasteurised product and −56.99 on the unpasteurised one), and the difference between the groups was not significant. Sauerkraut bacteria turned up in stool more often in the unpasteurised group. The authors read the result as pointing to the cabbage’s fermentation products and fibre more than to the live bacteria, while noting that the study was underpowered. It had no placebo group, so the improvement in both arms cannot be separated from a placebo effect.

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How Dead Microbes Are Thought to Act

A dead microbe cannot settle in the gut. The 2022 review states it plainly: “As postbiotics are composed of inanimate microorganisms, they cannot colonize the host. However, they can in theory modify the composition or functions of the host microbiota, although evidence for this is scarce.”

The 2021 consensus describes several proposed routes, most of them drawn from laboratory and animal work rather than proven in people:

• Immune signalling. Cell-wall pieces, pili and other surface molecules are recognised by the immune system’s pattern-recognition receptors whether the cell is alive or dead. The panel suggests that keeping cell structure intact may help — the cell wall protects active molecules from rapid digestion — but adds that “further experimental proof is needed.”
• Gut-barrier effects and metabolic effects through metabolites that come along with the cells, such as short-chain fatty acids, where they are present in enough quantity.
• Signals to the nervous system. Here the panel cites a counter-example: in a study in mice and in human gut organoids, serotonin induction by one bifidobacterium required live cells, and heat-killed cells did not reproduce it.

How a microbe is killed matters. The consensus notes that heat (pasteurisation, tyndallisation, autoclaving) is the usual method, that spray drying, high pressure, irradiation and other methods are alternatives, and that the method can change what the dead cells do. In one example it describes, spray drying left some cells live with intact pili and others inactivated without them; pili are surface structures linked to how bacteria interact with the immune system. This is the reason the definition ties a postbiotic to a specific preparation rather than to a species.

For the live-bacteria side of these mechanisms, and the role of fibre-derived butyrate in the gut wall, see the interactive Gut Barrier and Your Microbiome animation.

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Human Trials: Irritable Bowel Syndrome and the Gut

The largest single trial. A randomised, double-blind, placebo-controlled trial at 20 sites in Germany (Andresen and colleagues, 2020) gave 443 adults with irritable bowel syndrome either two placebo capsules or two capsules holding a combined 1 × 10⁹ heat-inactivated cells of Bifidobacterium bifidum MIMBb75 once a day for 8 weeks. The main outcome combined at least a 30% drop in abdominal pain with adequate relief of overall symptoms in at least 4 of the 8 weeks. It was reached by 74 of 221 people (34%) on the heat-killed bacteria and 43 of 222 (19%) on placebo (risk ratio 1.7). Put the other way, 66% of the treated group and 81% of the placebo group did not reach it. No serious adverse events occurred in the treated group; tolerability was rated good or very good by 91% versus 86%. The authors concluded that the strain’s effects are “mediated independently of cell viability.” The trial was funded by the maker of the product.

The pooled evidence. A 2026 systematic review and meta-analysis (Ayad and colleagues) found four randomised controlled trials of postbiotics against placebo in adults with irritable bowel syndrome, with 1,062 participants in all. Postbiotics lowered symptom-severity scores (standardised mean difference −1.36) and raised the chance of a meaningful pain response (risk ratio 2.46). Quality of life improved with capsules but not when an enema-based study was included, and adverse-event rates were similar to placebo. The authors rated the certainty of the evidence as low, with moderate to substantial differences between trials, and called for larger, standardised trials.

The consensus statement’s own table also lists smaller adult gut studies with mixed results, including a 4-day study in 25 people with obstructive jaundice in which intestinal permeability rose in both the water and the inactivated-bacteria groups and showed only a trend toward normal with the live strain. For the wider evidence on irritable bowel syndrome, see the Irritable Bowel Syndrome page.

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Human Trials: Infant Formula and Childhood Infections

Infant formula. Formulas fermented with bacteria and then dried, so that few live cells remain, are among the postbiotic products already on sale. A 2022 updated systematic review (Szajewska and colleagues) found 11 randomised controlled trials comparing such formulas with standard formula. Five trials had a high overall risk of bias and six had “some concerns.” Most data came from formula fermented with Bifidobacterium breve C50 and Streptococcus thermophilus. The formulas were “safe and well tolerated by infants who cannot be breastfed,” but the review found that “no firm conclusion can, however, be reached regarding the clinical effects and benefit of one formula over another,” and that versions with further changes “did not offer clear benefits replicated in other studies.”

Diarrhoea and common infections in young children. A 2020 systematic review (Malagón-Rojas and colleagues) found seven randomised trials with 1,740 children under 5. In four treatment trials (224 children), heat-killed Lactobacillus acidophilus LB shortened diarrhoea by about 20 hours (mean difference −20.31 hours). In two prevention trials (537 children), heat-inactivated Lactobacillus paracasei CBA L74 lowered the risk of diarrhoea (relative risk 0.51), pharyngitis (0.31) and laryngitis (0.44). The reviewers still judged the evidence “limited” for recommending specific postbiotics.

One of those prevention trials (Corsello and colleagues, 2017) gave children aged 12 to 48 months who attended day care either 7 grams a day of cow’s milk fermented with L. paracasei CBA L74 or a maltodextrin placebo through a winter season. By intention-to-treat analysis, 60% of the fermented-milk group and 83% of the placebo group had at least one common infection in 3 months — so 40% and 17% had none. The consensus statement’s table also lists a Finnish trial in 41 children under 4 with rotavirus diarrhoea in which heat-inactivated and live Lactobacillus casei gave equal clinical recovery.

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Human Trials: Colds, Skin and Metabolism in Adults

Colds and upper-respiratory infections

Results here run in both directions.

• A randomised trial (Murata and colleagues, 2018) gave 241 healthy young adults heat-killed Lactobacillus paracasei MCC1849 at two doses, or placebo, daily for 12 weeks. Across the whole group there was no significant difference in how often people caught a cold. In a prespecified subgroup of people who had caught a cold in the previous year, cold incidence, days of symptoms and symptom scores improved on the lower dose and were only slightly lower on the higher dose.
• A randomised, double-blind trial (Hirose and colleagues, 2013) in 78 healthy adults with high work-stress scores gave a tablet of heat-killed Lactobacillus plantarum L-137 (10 mg) or placebo daily for 12 weeks. Upper-respiratory infections were significantly less frequent in the treated group; the abstract does not give the counts.
• The consensus statement also records a large trial of a bacterial lysate in 288 people with chronic obstructive pulmonary disease that “failed to meet its primary end point,” a reduction in flare-ups.

Skin: atopic dermatitis

A 2024 systematic review (Lima and Paulino) found nine randomised trials, with 512 people evaluated, of oral non-viable lactobacilli for atopic dermatitis (eczema), most alongside steroid creams. The three adult trials reported symptom improvement, but three of the six trials in children did not report results favouring the postbiotic. The reviewers concluded that the data “do not indicate efficacy in pediatric patients” so far, and that adults might benefit when it is used as an add-on. Mild side effects were reported in one study. A 2023 perspective by Vinderola and colleagues notes that postbiotic products are also being developed as cosmetics applied to the skin and for vaginal health. See the Eczema page for the condition itself.

Metabolism: pasteurised Akkermansia muciniphila

A randomised, double-blind, placebo-controlled pilot study (Depommier and colleagues, 2019) enrolled 40 overweight or obese, insulin-resistant volunteers; 32 completed it. They took 10¹⁰ cells a day of Akkermansia muciniphila, either live or pasteurised, or placebo for three months. Both forms were safe and well tolerated. Compared with placebo, the pasteurised bacteria improved insulin sensitivity by about 28.6%, lowered blood insulin by about 34.1% and total cholesterol by about 8.7%. Body weight fell by 2.27 kg compared with placebo, but this was not statistically significant (P = 0.091). The authors called it a proof-of-concept study; it is small, and two of its authors hold patents on the use of this bacterium.

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Claimed Advantages and the Safety Findings

Shelf life and storage

The 2021 consensus panel lists stability as “one important factor driving interest in postbiotics.” Many probiotic organisms are sensitive to oxygen and heat, and the panel writes that long shelf life “can be readily achieved for inanimate microorganisms.” It suggests postbiotics “might also be more suited” to regions without reliable refrigerated supply chains or where heat makes live products hard to store. The authors of the German irritable bowel syndrome trial gave a similar rationale: non-viable strains “might have advantages over viable bacteria for product stability and standardisation.” These are arguments made by researchers in the field; no trial on this page compared shelf life directly.

No live-bacteria infections

Live probiotics can, rarely, enter the bloodstream. A 2019 study of hospital intensive care unit patients (Yelin and colleagues) found a markedly higher risk of Lactobacillus bloodstream infection in patients given probiotics than in those not given them, and whole-genome sequencing showed that the bacteria in patients’ blood were genetically inseparable from the bacteria in the probiotic product. Some blood isolates had picked up new mutations, including one that gave antibiotic resistance.

The postbiotics consensus argues that postbiotics “could reasonably be expected to have a better safety profile than probiotics,” because killed microbes cannot multiply and therefore “cannot cause bacteraemia or fungaemia,” risks it describes as associated with probiotics “albeit extremely rare.” The German trial authors likewise cited “safety concerns” raised for patients susceptible to infection. The 2024 eczema review gave the same reason for interest in postbiotics.

What the safety argument does not cover

The same consensus states that postbiotics “cannot be presumed to be safe solely based on the safety profile of the progenitor microorganism.” Its example: lipopolysaccharide (endotoxin) from Gram-negative bacteria can trigger sepsis and toxic shock, and it can be released when those bacteria die. The panel calls for a safety assessment of every postbiotic for its intended use. In the trials above, adverse events were similar to placebo in the German irritable bowel syndrome trial and in the 2026 meta-analysis, and the infant-formula review found the formulas safe and well tolerated — but these trials were not designed to detect rare harms, and they enrolled mostly healthy people or outpatients rather than the severely ill or immune-suppressed. The German trial, for example, excluded people with chronic inflammatory bowel disease, cancer and autoimmune disease.

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What Is Not Known

• Whether dead and live versions of the same strain do the same thing. Few trials compare them head to head. The eczema review found two such comparisons, and only one reported benefit in both groups; the rotavirus trial found equal recovery; the jaundice study and the serotonin experiment found the live form did something the dead form did not.
• Whether results carry across strains or preparations. Under the consensus, each preparation — microbe, growth material and killing method — stands on its own evidence. A result for one heat-killed strain says nothing about another, or about the same strain killed a different way.
• Effects in healthy people. The 2022 review states that “overall, there is limited evidence for postbiotics in healthy populations.”
• Effects on the gut microbiome. In theory postbiotics may shift the resident microbes, but the 2022 review calls the evidence for this “scarce,” and in the Akkermansia pilot the overall structure of the gut microbiome did not change.
• What dead microbes in ordinary foods contribute. The consensus notes that the active molecules of fermented-food microbes are “thought to be similar to those produced by probiotics, but this link has not been conclusively established.” No trial cited here tested the dead-cell content of bread, soy sauce or cooked fermented soy.
• Long-term and rare harms, especially in people who are seriously ill, since trials so far are short and small.
• Regulation. The 2021 panel found that no regulator had adopted a postbiotic definition for foods or supplements, and that the United States Food and Drug Administration had not specifically addressed the term. The 2022 review repeated that no government or international agency had yet written the term into regulation.
• Independence of the research. Many panel members and trial authors declare consulting work or funding from companies that make probiotic, postbiotic or infant-formula products, and the German irritable bowel syndrome trial was funded by the product’s maker.

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Key Research Papers

1. 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;18(9):649-667. PubMed PMID: 33948025
2. Vinderola G, Sanders ME, Salminen S, Szajewska H. Postbiotics: The concept and their use in healthy populations. Front Nutr. 2022;9:1002213. PubMed PMID: 36570166
3. Vinderola G, Druart C, Gosálbez L, et al. Postbiotics in the medical field under the perspective of the ISAPP definition: scientific, regulatory, and marketing considerations. Front Pharmacol. 2023;14:1239745. PubMed PMID: 37745060
4. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. PubMed PMID: 24912386
5. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. PubMed PMID: 28611480
6. Swanson KS, Gibson GR, Hutkins R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. 2020;17(11):687-701. PubMed PMID: 32826966
7. Marco ML, Sanders ME, Gänzle M, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods. Nat Rev Gastroenterol Hepatol. 2021;18(3):196-208. PubMed PMID: 33398112
8. Nielsen ES, Garnås E, Jensen KJ, et al. Lacto-fermented sauerkraut improves symptoms in IBS patients independent of product pasteurisation - a pilot study. Food Funct. 2018;9(10):5323-5335. PubMed PMID: 30256365
9. Andresen V, Gschossmann J, Layer P. Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Lancet Gastroenterol Hepatol. 2020;5(7):658-666. PubMed PMID: 32277872
10. Ayad ME, Yu S, El Shennawy S, et al. Efficacy and Safety of Postbiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. J Gastroenterol Hepatol. 2026;41(7):1994-2005. PubMed PMID: 42103684
11. Szajewska H, Kołodziej M, Skórka A, et al. Infant Formulas With Postbiotics: An Updated Systematic Review. J Pediatr Gastroenterol Nutr. 2022;74(6):823-829. PubMed PMID: 35258495
12. Malagón-Rojas JN, Mantziari A, Salminen S, Szajewska H. Postbiotics for Preventing and Treating Common Infectious Diseases in Children: A Systematic Review. Nutrients. 2020;12(2):389. PubMed PMID: 32024037
13. Corsello G, Carta M, Marinello R, et al. Preventive Effect of Cow's Milk Fermented with Lactobacillus paracasei CBA L74 on Common Infectious Diseases in Children: A Multicenter Randomized Controlled Trial. Nutrients. 2017;9(7):669. PubMed PMID: 28654019
14. Murata M, Kondo J, Iwabuchi N, et al. Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults. Benef Microbes. 2018;9(6):855-864. PubMed PMID: 30099891
15. Hirose Y, Yamamoto Y, Yoshikai Y, Murosaki S. Oral intake of heat-killed Lactobacillus plantarum L-137 decreases the incidence of upper respiratory tract infection in healthy subjects with high levels of psychological stress. J Nutr Sci. 2013;2:e39. PubMed PMID: 25191589
16. Lima M, Paulino LC. Oral Postbiotics as a Therapeutic Strategy for Atopic Dermatitis: A Systematic Review of Randomized Controlled Trials. J Am Nutr Assoc. 2024;43(2):139-146. PubMed PMID: 37459239
17. Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096-1103. PubMed PMID: 31263284
18. Yelin I, Flett KB, Merakou C, et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat Med. 2019;25(11):1728-1732. PubMed PMID: 31700189

PubMed Topic Searches

1. PubMed: postbiotics in randomised controlled trials
2. PubMed: heat-killed lactobacilli in randomised trials
3. PubMed: fermented infant formula and postbiotics
4. PubMed: pasteurised fermented foods and health

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Connections

• Probiotics — the live organisms this page contrasts with
• Probiotics: History and Discovery — how the definitions came about
• Fermented Foods — the foods that carry live and dead microbes
• Natto, Bacillus subtilis and Gut Health — spores, heat and the fermented soy food
• Prebiotics — the fibres that feed resident microbes
• Resistant Starches — the fibre source of short-chain fatty acids
• Irritable Bowel Syndrome — where the largest postbiotic trials were run
• Eczema — the skin condition in the atopic dermatitis trials
• The Gut Barrier and Your Microbiome — interactive animation

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