Postbiotics

1. What Postbiotics Are

Postbiotics are defined, non-viable microbial cells or their components obtained from probiotics following fermentation or inactivation (e.g., via heat, radiation, or lysis). They include cell wall components, metabolites, enzymes, or signalling molecules such as short-chain fatty acids, exopolysaccharides, or bacteriocins. Production typically involves strains from the genera Lactobacillus, Bifidobacterium, or Pediococcus, with inactivation enhancing storage stability and eliminating safety risks associated with live microbes. Postbiotics are administered orally, topically, or in foods, where the matrix (e.g., milk ferments, capsules, serums) influences bioavailability.

Critical to the interpretation of studies is the diversity of preparations: postbiotics differ not only by source strain and inactivation method but also by composition (e.g., pure metabolites vs. cell debris) and purity. Even with the same strain, varying manufacturing processes can yield distinct efficacy profiles. The majority of controlled studies use strain-specific postbiotics (e.g., Lactobacillus paracasei ET-22 or Epidermidibacterium keratini EPI-7), whose results cannot be extrapolated to other preparations. Furthermore, standardised analytical methods for characterising active components are lacking, complicating comparisons between studies.

2. What the Studies Show in Detail

The key human studies and major reviews—by application area, including population, duration, preparation, outcome measures, and results as reported in the original publications. Figures are included only where the study provides them.

Distribution of controlled human studies by application area—note that the numbers are not additive, as a single study may be assigned to multiple areas:

Gut and Microbiome

In a randomised, placebo-controlled crossover study involving 69 young adults (36 in Group A, 33 in Group B), the effect of the postbiotic Probio-Eco® on chronic diarrhoea was investigated. Participants received either the postbiotic or a placebo for 21 days, followed by a 14-day washout phase and subsequent crossover of the intervention. Clinical symptoms (Bristol Stool Scale, defecation frequency, urgency, anxiety), gut microbiota composition, and metabolite profiles were assessed. Results showed a significant improvement in stool consistency, a reduction in defecation frequency and urgency, and decreased anxiety. Microbiota analysis revealed an increase in beneficial bacteria such as Dysosmobacter welbionis and Faecalibacterium prausnitzii, while potentially pathogenic species like Megamonas funiformis were reduced. Metabolomic analysis indicated an enrichment of health-promoting metabolites (e.g., α-linolenic acid, p-methoxycinnamic acid) and a decrease in diarrhoea-associated substances (e.g., theophylline, piperine, capsaicin). However, the study’s short intervention duration and specific population limit generalisability 4.

A randomised, double-blind, placebo-controlled study involving 68 participants with halitosis examined the effect of Lactobacillus paracasei ET-22 (both live and heat-inactivated) on oral microbiota and volatile sulphur compounds (VSCs). Participants took lozenges three times daily for four weeks. Both intervention groups (live and heat-inactivated) showed a significant reduction in VSC levels, with the live variant demonstrating a stronger effect (p = 0.0148). Additionally, the composition of volatile organic compounds (VOCs) in saliva changed, with a decrease in undesirable substances such as indole, pyridine, and nonanoic acid. The oral microbiota exhibited taxonomic shifts, though their clinical relevance remains unclear. The study is limited to halitosis and does not assess long-term effects 2.

In a randomised, controlled study involving 31 participants (15 placebo, 16 postbiotic), the effect of a postbiotic-containing toothpaste (3 × 10¹⁰ CFU inactivated Lactobacillus strains) on oral microbiota and immune parameters was investigated. After four weeks of use, levels of secretory immunoglobulin A (IgA) and acetic and propionic acids in saliva increased significantly (p < 0.05). Alpha diversity of the salivary microbiota rose, and the relative abundance of pathogenic species such as Enterobacteriaceae and Escherichia declined, while Ruminofilibacter and Lactobacillus increased. These changes persisted one month after discontinuing the toothpaste. However, the study is small and does not evaluate clinical endpoints such as caries or periodontitis 5.

A randomised, double-blind, placebo-controlled study involving 60 healthy Japanese women (aged 30–50 years) investigated the effect of heat-inactivated Latilactobacillus sakei KABP-065 (1 × 10¹⁰ cells/day) on skin parameters. After eight weeks of intake, the postbiotic group showed a significant improvement in skin elasticity compared to the placebo group. In a subgroup analysis (participants in their 40s), skin hydration and elasticity improved more markedly. The study suggests systemic effects but remains limited to a specific age group and ethnic population 7.

Hypothesis The observed effects on microbiota and metabolite profiles suggest that postbiotics may act via modulation of microbial communities and their metabolic products. In particular, the enrichment of short-chain fatty acids (e.g., butyrate) and the reduction of pro-inflammatory metabolites could provide mechanistic explanations. However, studies specifically testing these hypotheses and establishing causal relationships are currently lacking.

What is missing: long-term studies with larger, more diverse populations investigating clinically relevant endpoints (e.g., remission in chronic diarrhoea, infection prevention) and mechanistic insights into the interaction between postbiotics, microbiota, and host physiology.

Inflammatory Processes

A randomised, double-blind, placebo-controlled study involving 60 NSCLC patients (30 per group) examined the effect of the postbiotic JK5G in combination with immune checkpoint inhibitors (ICIs) and chemotherapy. Patients received either JK5G or placebo over four cycles (each three weeks). The primary endpoint was objective response rate (ORR), with secondary endpoints including quality of life, adverse effects, gut microbiota, inflammatory markers, and lymphocyte subsets. ORR did not differ significantly between groups (36.67% vs. 50%, p = 0.297). However, the JK5G group showed better quality of life, higher nutrient levels, and reduced depressive symptoms (all p < 0.05). Gut microbiota diversity increased, with a rise in Bacteroides and Faecalibacterium, while inflammatory markers such as IL-6 and TNF-α were reduced. The study is limited to NSCLC patients and does not assess long-term survival data 3.

A systematic review and meta-analysis of 25 randomised controlled trials (RCTs) analysed the effect of postbiotic-containing interventions on metabolic parameters. The analysis showed a significant reduction in serum insulin (-2.76 µU/mL), triglycerides (-8.46 mg/dL), waist circumference (-1.47 cm), and CRP (-0.99 mg/L). No significant effects were observed for fasting blood glucose, HOMA-IR, HbA1c, blood pressure, or BMI. Subgroup analyses suggested stronger effects in younger participants and with longer intervention durations. The meta-analysis aggregates heterogeneous studies, whose results may be influenced by varying strains, dosages, and additional components, and does not isolate the effect of postbiotics alone 6.

In a randomised, double-blind, placebo-controlled study involving 60 female patients with vulvar lichen sclerosus (VLS), the effect of a postbiotic derived from Lactobacillus crispatus NCU-31 in combination with topical glucocorticoids was investigated. Compared to healthy participants, VLS patients exhibited increased microbial diversity and a reduced prevalence of Lactobacillus, while Prevotella, Gardnerella, and Streptococcus were more abundant. The combination therapy resulted in a significant improvement in clinical scores (Cattaneo Clinical Score, IGA) and quality of life (DLQI, VQLI) compared to the placebo group. The study demonstrates promising results but is limited to a specific indication and a small population 9.

Hypothesis The observed effects on inflammatory markers and microbiota suggest that postbiotics may exert anti-inflammatory actions through modulation of the immune response and promotion of a healthy microbiota. In particular, the reduction in CRP and pro-inflammatory cytokines indicates a potential systemic effect, though further mechanistic investigation is required.

What is lacking: Studies that specifically elucidate the anti-inflammatory mechanisms of postbiotics, particularly regarding their interaction with the immune system and the long-term clinical relevance in chronic inflammatory diseases.

Immune System

A pilot double-blind, randomised, placebo-controlled study involving 41 preterm infants (<36 weeks gestational age) examined the effect of heat-inactivated Pediococcus acidilactici K15 on respiratory infections. Participants received K15 or placebo once daily for one year. No significant difference was observed in the number of febrile days (4.5 vs. 6.6 days). However, a subgroup analysis revealed a more pronounced effect in children with older siblings. Faecal microbiota analysis showed an enrichment of Faecalimonas, which may promote butyrate production. The study is small and does not investigate specific infectious pathogens or immune parameters 34.

Hypothesis The observed enrichment of butyrate-producing bacteria may indicate an immunomodulatory effect of postbiotics, mediated through the promotion of a healthy gut microbiota. However, direct evidence for a causal role of these microbes in infection prevention is lacking.

What is lacking: Larger studies with specific immune endpoints (e.g., antibody response, cytokine profiles) and longer follow-up periods to investigate the immunomodulatory effects of postbiotics in vulnerable populations such as preterm infants.

Skin

A randomised, double-blind, placebo-controlled study involving 100 healthy adults with periorbital wrinkles investigated the effect of heat-inactivated Lactobacillus acidophilus IDCC 3302 (ID-ACT 3302) on skin ageing parameters. Participants received the postbiotic or placebo daily for 12 weeks. The primary endpoint was the change in crow’s feet wrinkles, with secondary endpoints including skin hydration, transepidermal water loss (TEWL), skin elasticity, and global improvement scores. The postbiotic group showed no superiority over placebo in wrinkle endpoints but demonstrated a significant improvement in the elasticity index R2. Skin hydration and TEWL improved in both groups.

In a randomised, controlled split-face study involving Asian women, the topical application of a ferment filtrate from Epidermidibacterium keratini EPI-7 (a postbiotic) was investigated for its effects on skin ageing parameters. The application led to significant improvements in skin barrier function, elasticity, and dermal density compared to the placebo group. Additionally, the prevalence of commensal skin microbes such as Cutibacterium, Staphylococcus, and Lactobacillus increased, while the diversity of the skin microbiota rose. The study is limited to topical application and a specific population 1.

Hypothesis The observed effects on skin microbiota and skin parameters may indicate an interaction between postbiotics and the skin barrier, mediated through modulation of the microbiota and the production of antimicrobial metabolites. However, direct evidence for the underlying mechanisms is lacking.

What is lacking: Studies that specifically investigate the systemic and topical mechanisms of action of postbiotics on the skin barrier and skin microbiota, particularly regarding long-term effects and applicability across different skin types and ethnic groups.

Overall Picture

The available studies suggest that postbiotics may influence various applications—from modulating gut microbiota and reducing inflammatory markers in preclinical settings to improving skin parameters in clinical trials. Particularly consistent are the findings on microbiota composition and the enrichment of health-promoting metabolites (e.g., short-chain fatty acids) in animal and cell culture models. Clinical studies demonstrate improvements in chronic diarrhoea, halitosis, skin elasticity, and inflammatory parameters, though often in small, specific populations and with limited duration. The effects on inflammatory markers and metabolites remain preclinical and have not yet been confirmed in human trials.

Evidence for clinically relevant efficacy in controlled human studies is still in its early stages in many areas. In particular, mechanistic links, long-term effects, and the generalisability of results to broader populations stand out as open research questions. Additionally, the postbiotic strains and preparations studied are heterogeneous, complicating the comparability of results.

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3. How Robust the Research Is

The evaluated studies include a subset of human research, among them controlled intervention trials. The research focuses on gut-associated applications, followed by safety assessments, skin, and the immune system. The most frequently cited controlled studies investigate skin ageing, halitosis, diarrhoea, and oncological side effects, with application forms ranging from oral capsules to cosmetic serums. A notable feature is the diversity of outcome measures: while some studies assess clinical symptoms (e.g., skin elasticity, stool frequency), others are limited to surrogate markers such as microbiome composition or inflammatory parameters.

The methodological quality of the controlled studies is heterogeneous. Strengths include randomised, double-blind designs and the use of placebo controls, particularly in topical applications. Weaknesses are evident in small sample sizes (often pilot studies) and short intervention periods, which preclude conclusions about long-term effects. Furthermore, dose-finding studies are frequently lacking, rendering the chosen concentrations appear arbitrary. Review articles are dominated by mechanistic hypotheses (e.g., modulation of the gut-brain axis or vagus nerve stimulation), yet these mechanisms remain unconfirmed in humans. Preclinical studies (animal and cell models) provide only indications of potential pathways, such as the regulation of tight junction proteins or cytokine patterns in vitro or in animals; their relevance for human clinical outcomes is not yet investigated.

4. Common Claims — and What the Data Show

5. Profile: Molecule and Charge

Postbiotics are not a single molecule but a mixture — there is no empirical formula or fixed molecular mass. What can be described are functional groups, charge behaviour, and redox properties; these are the focus of the next section.

6. Charge, Electrons, Radicals

In cell cultures, the antioxidant effects of postbiotics were demonstrated using radical-scavenging assays such as ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulphonic acid)), where free radicals were neutralised 21. Further tests included measuring the iron-reducing antioxidant capacity and the reduction of reactive oxygen species (ROS) 22. Postbiotics influenced ROS levels in hydrogen peroxide-induced cells, suggesting modulation of oxidative stress 23 24. In foundational studies, a ROS-dependent bactericidal effect was described, which could be inhibited by radical scavengers such as thiourea 26. Whether these effects are due to charge transfer or cation exchange is not specified in the available studies.

No direct measurements of the electrochemical properties of postbiotics have been conducted in humans. Observations indicate, however, that microbial enzymes during fermentation generate organic acids and bioactive peptides, which could indirectly influence redox-active processes 20. In cell cultures, a significant inhibition of ROS production by postbiotic extracts was demonstrated, suggesting an antioxidant effect. Whether these effects are attributable to electron transfer or radical binding remains to be investigated. Foundational studies describe postbiotics as radical scavengers that reduce oxidative stress 25. However, whether similar mechanisms occur in humans is not supported by electrochemical measurements. Further research on charge distribution or cation exchange capacity would be necessary.

7. Interactions with Other Substances

Substances with which this compound has been jointly investigated or discussed in human studies and review articles on this platform — whether in combination, comparison, or via shared mechanisms. The number indicates studies in which both appear.

Data on interactions between postbiotics and medications or nutrients are limited. One human observation describes the combination of postbiotics (JK5G, JK21) with R-CHOP in high-risk DLBCL (IPI score 4), with no evidence of adverse interactions 27. In vitro studies using human intestinal cell lines (Caco-2, HT-29) show no cytotoxicity or genotoxicity with formulations derived from cell-free supernatant and heat-inactivated bacteria. Animal studies suggest synergistic effects: postbiotics (0.30%) enhanced growth and immune response in broilers when combined with inulin (1.0%) 30. Additionally, an interaction with nutrients was observed, where fish oil (enriched with docosahexaenoate) and medium-chain triglycerides altered the plasma lipidomes of cats and reduced putrefactive postbiotics in the bloodstream 33.

Direct evidence of effects on enzymes or metabolic pathways is lacking, but indirect indications exist. Postbiotics modulate host metabolism and immune responses via microbial metabolites that interact with signalling pathways 12 29. In vitro data show that certain postbiotics (e.g., from A. muciniphila, F. prausnitzii) can reduce the expression of ACE, ATR1, and ACE2 in human tissue, suggesting an influence on renin-angiotensin system-related genes 28. Cell culture studies demonstrate synergistic antibacterial effects of postbiotics (L. paracasei SD1, L. rhamnosus SD11) in combination with glycerol monolaurate or poly-L-lysine against H. pylori 31 31. Nutrient-dependent metabolic shifts were observed in consortia under rumen-like conditions, where nitrogen enrichment and carbon limitation promoted the production of branched short-chain fatty acids 32.

8. Overdose, Tolerability, and Limits

No specific dosage thresholds or systematic investigations regarding overdose, toxicity, or upper limits of postbiotics are available. In controlled human studies, no severe adverse effects were observed, even with prolonged use. For example, a 12-week supplementation with ID-ACT 3302 showed no serious side effects, and safety was comparable to placebo 11. A four-week study with KABP-065 postbiotics demonstrated no worsening of gastrointestinal symptoms; the frequency of adverse events did not differ from the placebo group 7. Similarly, no associated side effects were reported with K15 intake in preterm infants 34.

Contraindications are not explicitly established due to a lack of clinical data on at-risk groups. Postbiotics are considered safer than live microorganisms, though evidence remains limited 5 10. Observational studies suggest that microbiota interventions—including postbiotics—may influence the tolerability of therapies such as chemotherapy or immune checkpoint blockade, without identifying specific dose-response relationships or contraindications 17. Adverse effects in controlled studies were not systematically linked to particular dosages. Long-term effects, interactions with medications, and individual factors such as immune status or pre-existing conditions warrant further investigation. No animal or tissue studies on toxicity or upper limits are available.

9. The Most Robust Studies

Ranked by evidential strength, not by prominence. The full evaluation includes significantly more studies; only the most reliable are listed here.

Controlled Human Studies

• 1 Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study (2023)
• 2 Lactobacillus paracasei ET-22 and derived postbiotics reduce halitosis and modulate oral microbiome dysregulation: a randomised, double-blind, placebo-controlled study (2023)
• 3 JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomised controlled trial in China (2023)
• 4 Effects of postbiotics on chronic diarrhoea in young adults: a randomised, double-blind, placebo-controlled crossover trial assessing clinical symptoms (2024)
• 5 Evaluating the Role of Postbiotics in the Modulation of Human Oral Microbiota: A Randomised Controlled Clinical Trial (2025)
• 6 The effect of postbiotics supplementation on obesity and metabolic health: a systematic review and meta-analysis of randomised controlled trials (2025)
• The Effectiveness of Heat-Killed Pediococcus acidilactici K15 in Preventing Respiratory Tract Infections in Preterm Infants: A Pilot Study (2024)
• 7 Novel Application of Oral Postbiotics for Skin Condition in Healthy Middle-Aged Women: A Randomised, Double-Blind, and Placebo-Controlled Study (2025)
• 8 Pilot Study on the Effects of a Cosmetic Serum Containing Niacinamide, Postbiotics and Peptides on Facial Skin in Healthy Participants: A Randomised Controlled Trial (2024)
• A Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Limosilactobacillus fermentum K8-Lb1 Postbiotic on Weight Management (2026)
• 9 Postbiotics originated from Lactobacillus crispatus NCU-31 improves vulvar lichen sclerosus: a randomised, double-blind controlled trial (2026)
• 10 A Heat-Inactivated Two-Strain Lacticaseibacillus paracasei Fermented Milk as a Postbiotic for Functional Constipation: A Randomised Controlled Trial (2026)
• 11 Effects of Heat-Killed Lactobacillus acidophilus IDCC 3302 on Skin Ageing Parameters: A Randomised, Double-Blind, Placebo-Controlled Trial (2026)

Observational Studies in Humans

• Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications (2022)
• 12 Roles of the Intestinal Microbiota and Microbial Metabolites in Acute GVHD (2021)
• 13 Pre-, Pro-, Syn-, and Postbiotics in Infant Formulas: What Are the Immune Benefits for Infants? (2023)
• 14 Effect of Gut Microbiota-Derived Metabolites on Immune Checkpoint Inhibitor Therapy: Enemy or Friend? (2022)
• 15 Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies (2025)
• 16 The Modulation Effect of a Fermented Bee Pollen Postbiotic on Cardiovascular Microbiota and Therapeutic Perspectives (2023)
• 17 The Emerging Role of Microbiota in Lung Cancer: A New Perspective on Lung Cancer Development and Treatment (2025)
• 18 Dysbiosis–NK Cell Crosstalk in Pancreatic Cancer: Toward a Unified Biomarker Signature for Improved Clinical Outcomes (2025)
• The Microbiome and Uremic Solutes (2022)
• 19 The Role of Postbiotics in Asthma Treatment (2024)
• Critical Role of Reproductive Tract Microbiota and Derived Metabolites in Inflammation, Tumour Immunity, and Tumourigenesis of Gynaecological Cancers: A Review (2026)

10. Summary

Postbiotics represent an emerging field of research with findings on gut-associated applications, skin, and immune modulation from controlled human studies. These studies suggest strain- and preparation-specific effects, such as in diarrhoea, skin ageing, or immune-related adverse effects of oncological therapies. The methodological quality of these studies is heterogeneous: while randomised, double-blind designs with placebo controls (particularly in topical applications) are convincing, small sample sizes, short intervention periods, and the absence of dose-finding studies limit their validity. The observed effects are often transient and cease upon discontinuation, suggesting no sustained modulation of the microbiome or systemic effects. Nevertheless, the data indicate a favourable safety profile, as even with prolonged use, no severe adverse effects have been documented.

Hypothesis The mechanistic hypotheses regarding postbiotics—such as modulation of the gut-brain axis, TLR4 activation, or butyrate-mediated histone acetylation—are plausible, yet causal evidence in humans is lacking. Preclinical studies (animal and cell models) provide indications of potential mechanisms, such as the regulation of tight junction proteins or cytokine patterns, but these findings remain preclinical and do not confirm such effects in humans. Should the local effects be confirmed in larger, long-term human studies, postbiotics could establish themselves as a safe alternative or adjunct to probiotics—particularly in areas where live microbes pose risks (e.g., immunosuppression). Furthermore, they may play a role in personalised medicine if strain- and preparation-specific efficacy profiles can be standardised. Hypothesis: The antioxidant properties of postbiotics, demonstrated in cell cultures via radical-scavenging assays, suggest a potential modulation of oxidative stress in preclinical settings, but whether these effects translate to humans remains unclear. Electrochemical measurements of charge distribution or cation exchange capacity could provide further insights.

To clarify the clinical relevance of postbiotics, replication studies using identical preparations, standardised endpoints, and adequately powered sample sizes are essential. Dose-finding studies should be prioritised to define effective concentrations and avoid arbitrary dosing. Additionally, long-term studies are needed to assess the safety and sustainability of effects, particularly regarding immunogenic reactions. For systemic applications (e.g., cognition, metabolism), robust data are currently lacking—controlled studies with clinical endpoints would be necessary to validate the hypothetical effects. Further research is also required in standardising analytical methods to characterise the active components of postbiotics and enable comparisons between studies. Finally, direct comparative studies between postbiotics and probiotics should be conducted to determine whether substitution or combination is beneficial. Without such studies, the generalisability of findings remains limited, and postbiotics remain a promising but insufficiently validated field of research.

11. Unresolved Questions

• Dose-response relationship: What concentrations are optimal for which applications? Systematic dose-finding studies are currently lacking.
• Long-term effects: Most studies last only weeks. It remains unclear whether effects persist after discontinuation or if continuous administration is required.
• Mechanistic validation: The postulated mechanisms (e.g., vagus nerve stimulation, SCFA signalling) have not been confirmed in humans.

12. Further Paths

Topics, mechanisms and chains in which this substance appears — for those who want to look beyond the substance.

• Interaction network