• Postbiotics as Emerging Functional Compounds in the Advancement of Functional Foods
  • Marjan Rouhi,1 Marjaneh sedaghati,2,* Mozhgan Emtyazjoo,3 Mohaddeseh Larypoor,4 Babak karami,5
    1. Department of Food science and Technology, NT.C., Islamic Azad University, Tehran, Iran
    2. Department of Food science and Technology, NT.C., Islamic Azad University, Tehran, Iran
    3. Department of Marine biology, NT.C., Islamic Azad University, Tehran, Iran
    4. Department of Microbiology, NT.C., Islamic Azad University, Tehran, Iran
    5. Department of Food science and Technology, NT.C., Islamic Azad University, Tehran, Iran


  • Introduction: Food is an essential human need, providing vital nutrients for growth, immune defense, and overall health. The human gut microbiota, composed of diverse beneficial microorganisms, plays a crucial role in maintaining host health through immune modulation, enhancement of gut barrier function, and protection against pathogens. Postbiotics—defined as non-viable microorganisms or their components that confer health benefits to the host—have recently emerged as a promising category of next-generation functional compounds. Unlike probiotics, which require survival and colonization in the gastrointestinal tract, postbiotics are more stable, safer, and easier to incorporate into food systems. Scientific studies have demonstrated a broad range of bioactivities associated with postbiotics, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of the gut microbiota. These properties make them potentially effective in preventing or managing chronic conditions such as obesity, type 2 diabetes, metabolic-associated steatotic liver disease (MASLD), and even certain cancers. Moreover, the integration of postbiotics in functional food formulations and bioactive packaging materials offers innovative approaches to enhance food safety, shelf life, and consumer health. Despite their advantages, further research is needed to elucidate the underlying mechanisms of action, determine optimal dosages, and assess safety in vulnerable populations. Combining postbiotics with other therapeutic or nutritional strategies holds great promise in advancing personalized and preventive health interventions. Keywords: Postbiotics, Probiotics, Functional foods, Gut microbiota, Immune system, Health promotion.
  • Methods: Food is one of the fundamental human needs and plays a key role in providing essential nutrients required for growth, physiological functions, immune enhancement, and maintaining health. One of the critical factors influencing human health is the gut microbiota, composed of a consortium of beneficial microorganisms. Numerous studies have shown that the composition and functionality of these microbes are determinative in host metabolic health, immune function, and even psychological status (Rad et al., 2021; Abate et al., 2022). In recent years, the use of bioactive compounds such as probiotics, prebiotics, and synbiotics has garnered increasing attention in the food and pharmaceutical industries. However, the use of live microorganisms may pose certain risks for specific populations, such as immunocompromised individuals. These risks include opportunistic infections and microbial imbalances. Additionally, the low stability of live microbes during food processing and storage presents a major challenge for their industrial application. In this context, postbiotics—compounds derived from non-viable microorganisms or their cellular components—have emerged as a promising alternative to probiotics due to their improved safety, high stability, and independence from viability (Salminen et al., 2021; Ma et al., 2023). These compounds not only contribute to enhancing intestinal epithelial barrier function and modulating immune responses but may also play a role in preventing diseases such as metabolic syndrome, inflammatory disorders, and even mental health conditions by modulating the gut microbiota (Hosomi et al., 2022; Le Roy et al., 2022). This review aims to explore the fundamental concepts and current scientific findings on postbiotics, with a focus on their role in promoting health, their industrial applications in the production of functional foods, and the challenges associated with their implementation. Mechanisms of Action of Postbiotics The concept of postbiotics as a new generation of functional bioactive compounds has emerged from expanding research on probiotics. In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined postbiotics as: "A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" (Salminen et al., 2021). According to this definition, only microorganisms with well-defined origin and confirmed safety can be used in postbiotic production. Despite being inanimate, postbiotics exert their biological effects through several mechanisms, including: Antimicrobial activity: Many postbiotics can inhibit pathogen growth through the production of organic acids, bacteriocins, and bioactive peptides. Antioxidant activity: Certain non-viable metabolites derived from probiotics, such as exopolysaccharides (EPS) and lipoteichoic acid, can protect against oxidative damage by scavenging free radicals (Sanaei et al., 2021). Immune modulation: Postbiotics can interact with immune cells through their structural components—such as lipoteichoic acids, muramyl peptides, and lipopolysaccharides—thus modulating innate and adaptive immune responses (Karim et al., 2024). Enhancement of intestinal barrier function: Some postbiotics stimulate mucus secretion, strengthen epithelial tight junctions, and reduce intestinal permeability, thereby preventing inflammation and antigen translocation (Ma et al., 2023). Modulation of gut microbiota: Although postbiotics do not directly increase microbial populations, they can support the growth of beneficial microbes and inhibit pathogens through competitive exclusion, contributing to microbiota balance. Postbiotics also have notable effects on metabolism, particularly in studies demonstrating their role in regulating lipid and glucose metabolism and inflammatory responses in chronic diseases such as obesity, MASLD, and type 2 diabetes (Fang et al., 2024; Xie et al., 2023). Despite encouraging evidence, challenges remain in fully elucidating the molecular mechanisms of postbiotic action. Therefore, more comprehensive clinical and molecular studies are warranted in this field. Sources of Postbiotics Postbiotics are primarily derived from microorganisms with well-characterized origins. These sources include traditional probiotics, next-generation probiotics, and other gut-native or fermentation-derived microorganisms. The bioactive compounds produced by these microbes include metabolites, structural components, enzymes, and intercellular signaling molecules, all of which have the potential to influence host health. Traditional Probiotics Species such as Lactobacillus and Bifidobacterium are well-known sources of postbiotics. During their growth and fermentation, they secrete various bioactive compounds, including exopolysaccharides (EPS), short-chain fatty acids (SCFAs), and antimicrobial agents. For instance, Lactobacillus helveticus is capable of producing polysaccharides with prebiotic and immunomodulatory properties (Wang et al., 2022). In Bifidobacterium strains, metabolites such as unsaturated fatty acids and neurotransmitters have also been identified (Li et al., 2022). Next-Generation Probiotics Microorganisms such as Akkermansia muciniphila and Bacteroides fragilis belong to this group. Their derived bioactive compounds—such as capsular polysaccharides (PSA), butyrate, and immune-regulating alkaloids—can modulate inflammatory pathways like TLR4/NF-κB and bile acid metabolism (Wang et al., 2021; Xie et al., 2023). Butyrate produced by Faecalibacterium prausnitzii has also shown protective effects against kidney diseases via the GPR43 axis (Li, Xu et al., 2022). Other Microbial Sources Additional sources include various gut-derived strains and microorganisms isolated from fermented foods such as kefir. Kefir grains comprise a consortium of lactic acid bacteria, yeasts, and acetic acid bacteria that can improve microbial balance through the production of organic acids and bioactive polysaccharides (Tan et al., 2022). It is noteworthy that even within a single microbial species, the type and quantity of postbiotic compounds can vary significantly depending on environmental conditions, nutrient sources, and culture parameters. This highlights the importance of optimizing culture media composition, temperature, pH, and nutritional elements in postbiotic production (Wei et al., 2024). Postbiotic Preparation The preparation of postbiotics involves a series of defined steps aimed at producing bioactive compounds from inactivated microorganisms. Various factors—including the microbial strain, culture conditions, cell disruption methods, and extraction techniques—affect the yield and quality of the final product. In general, postbiotic preparation includes the following stages: Microorganism Cultivation In the first step, selected strains with well-defined origins are cultured under controlled conditions to maximize biomass production. The composition of the culture medium, pH, temperature, aeration, and fermentation duration all influence the nature and amount of postbiotic compounds produced. Microbial Inactivation Following sufficient growth, microbial cells are inactivated using thermal, mechanical, or chemical methods. Novel approaches include heat treatment, ultrasound, high-pressure processing, ohmic heating, pulsed light, supercritical carbon dioxide, and cold plasma technology (Wei et al., 2024). The goal is to eliminate cellular viability while preserving the structural integrity and bioactivity of microbial components. Extraction and Purification After inactivation, cellular components—including the cell wall, membrane, secreted metabolites, and intracellular contents—are separated using techniques such as centrifugation, ultrafiltration, or solvent extraction. The method of extraction determines the type and functionality of the final postbiotic product. Identification and Quality Control To confirm successful inactivation, negative culture tests are performed to ensure the absence of live cells (Vale et al., 2023). Subsequently, qualitative and quantitative analyses of the bioactive compounds are conducted using analytical techniques such as chromatography, Fourier-transform infrared spectroscopy (FTIR), spectrophotometry, nuclear magnetic resonance (NMR), and mass spectrometry (Moradi et al., 2021). Ultimately, the final postbiotic product—either in liquid or dried form—can be incorporated into formulations for functional foods, dietary supplements, or bioactive packaging materials. Therapeutic Effects and Applications of Postbiotics Postbiotics, due to their wide range of bioactive compounds, possess significant therapeutic and nutritional potential. These compounds can modulate host physiological functions and contribute to the prevention and treatment of various diseases. The most well-known effects and applications of postbiotics include: immunomodulation and Anti-inflammatory Effects Postbiotics can regulate both innate and adaptive immune responses through cell wall components such as lipopolysaccharides, peptidoglycans, lipoteichoic acids, and flagellin. These immunomodulatory properties are particularly important in the prevention of inflammatory bowel diseases (IBD), allergies, and autoimmune disorders (Karim, 2024; Sanaei et al., 2021). Improvement of Metabolic Health Clinical and preclinical studies have demonstrated that postbiotics can improve gut microbiota composition, reduce intestinal permeability, and modulate inflammatory pathways. These effects contribute to the control of metabolic disorders such as type 2 diabetes, insulin resistance, and obesity (Fang et al., 2024). Certain postbiotic compounds, particularly short-chain fatty acids (SCFAs), directly influence host metabolism and act as regulators of endocrine function. Hepatic Health and Liver Disease In animal and in vitro studies, postbiotics have shown beneficial effects in reducing inflammation, steatosis, and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). These effects are mediated through enhanced intestinal barrier function and improved lipid metabolism (Yilmaz, 2024). Anticancer Properties Postbiotic compounds such as SCFAs, bacteriocins, polyphenols, and probiotic-derived metabolites exhibit anti-tumor potential by inhibiting tumor cell proliferation, inducing apoptosis, and enhancing antitumor immune responses. These properties make postbiotics promising candidates for adjunct cancer therapies (Sudaarsan & Ghosh, 2024). Food and Biotechnological Applications Owing to their antimicrobial, antioxidant, and high stability properties, postbiotics are used in the food industry as natural preservatives and functional additives. Compounds like bacteriocins, organic acids, and bioactive peptides are effective in controlling pathogen growth and extending shelf life (Sharafi et al., 2023). Postbiotics are also being utilized in the development of bioactive packaging materials. Safety Assessment and Challenges of Postbiotics One of the major advantages of postbiotics over probiotics is their enhanced safety profile, as they contain no live cells and thus eliminate risks associated with uncontrolled microbial proliferation or horizontal gene transfer of antibiotic resistance. However, comprehensive safety evaluations are still required, particularly for vulnerable populations such as immunocompromised individuals, the elderly, and infants. Existing Safety Evidence Most human and animal studies report that postbiotics are safe and well-tolerated (Wei et al., 2024). Nevertheless, some clinical trials have noted mild to moderate side effects, including vomiting, bloating, and dehydration in children receiving inactivated Lactobacillus acidophilus (Malagón-Rojas et al., 2020). Research Limitations Unlike probiotics, clinical studies on postbiotics remain limited. In many cases, postbiotics are administered alongside prebiotics or other compounds, complicating the interpretation of their independent effects. Additionally, variations in composition and preparation methods hinder cross-study comparisons. Need for Standardization For broader application in food and pharmaceutical industries, it is essential to standardize production processes, determine the exact composition of active ingredients, and conduct long-term safety assessments. Moreover, the safety profile of postbiotics derived from less-studied microbial strains needs thorough investigation.
  • Results: Recommendations for Future Research Future studies should focus on the following: Designing clinical trials with defined compositions and controlled dosages Evaluating effects in high-risk groups (infants, elderly, chronically ill) Investigating detailed mechanisms of action, absorption, and metabolism Assessing potential synergistic effects with other therapies or dietary supplements Despite current challenges, the unique biological features of postbiotics—including high stability, relative safety, and independence from viability—position them as promising agents in clinical nutrition and the development of functional foods.
  • Conclusion: Based on current scientific evidence, postbiotics have emerged as a new generation of functional bioactive compounds with a promising role in promoting human health and advancing the development of functional foods. These compounds, endowed with antioxidant, anti-inflammatory, immunomodulatory, and metabolic regulatory properties, have demonstrated significant potential in the prevention and management of various diseases such as metabolic disorders, liver diseases, and even cancer. Unlike probiotics, postbiotics offer several advantages, including high stability, independence from viability, enhanced safety, and ease of formulation for industrial applications. These features make them suitable candidates for incorporation into nutritional supplements, functional food products, and innovative bioactive packaging systems. Nevertheless, to ensure the safe and effective use of postbiotics on a broad scale, further research is needed to clarify their mechanisms of action, standardize production processes, determine optimal dosages, and assess safety in specific populations. Moreover, combining postbiotics with other nutritional and therapeutic strategies could open new avenues in personalized nutrition and targeted disease prevention.
  • Keywords: Postbiotics, Probiotics, Functional foods, Gut microbiota, Immune system, Health promotion.