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Postbiotics: a Research Guide Although advantages of using postbiotics might be exciting, it needs to be noted that further research is needed to confirm their effectiveness and confirm their safety. This research guide dives into the definition of post- biotics, the difference between biotics products, postbiotic product applications, clinical im- plications and methods, current clinical trends and an outline of the future opportunities for the industry.
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Contents 2 - Introduction 3 - What are postbiotics? 4 - Prebiotics vs probiotics vs postbiotics: What is the difference? 5 - Postbiotics and their microbial producers
7 - Postbiotic product applications 9 - Clinical implications and methods 12 - Clinical trial summary 13 - Postbiotics future opportunities for the industry 14 - About Atlantia
INTRODUCTION
Recent understanding of the microbiome‘s role in health and disease prompted the development of innovative solutions that will help modulate its composition and restore its appropriate func- tion. Postbiotics, as a wide collection of non-via- ble cells, metabolites, and bioactive components of microbial origin, are examples of the prepara- tions, when applied, that might bring benefits for the human body. Although the potential of these bioactives might vary greatly, the majority of them have been attributed with potent antimicrobial, antioxidant and immunomodulatory properties, which can lead to favourable physiological, immu- nological, neuro-hormonal, regulatory and met-
abolic responses. Postbiotics, in comparison to probiotics, prebiotics or synbiotics, a combination of both, have additional benefits of extended shelf- life, better stability and no need for use of live mi- croorganisms making them appealing as nutrition- al additives and preservatives of food products, as well as treatments targeted to individuals with dysregulated immune function or small children (Żółkiewicz et al., 2020). Although the advantages of using postbiotics might be exciting, it needs to be noted that further research is needed to con- firm their effectiveness and safety to improve their function and clinical validity.
WHAT ARE POSTBIOTICS?
Postbiotics are a broad collection of health-pro- moting soluble compounds and substances secret- ed by microorganisms or released after bacterial lysis. Examples of these compounds, also referred to as metabiotics, include microbial proteins/pep- tides, enzymes (e.g. superoxide dismutase (SOD), glutathione peroxidase (GPx)), organic acids, short chain fatty acids (SCFAs), vitamins, cofactors, cell- free supernatants, exopolysaccharides, cell wall fragments, carbohydrates, bacterial lysates, im- mune-signalling molecules, bacteriocins, metab- olites, neurotransmitters, flavonoids, terpenoids, and phenolic derivatives. Postbiotics have many potential benefits for the human body, in partic- ularly for gut, immune, vascular and neurological functions (Puccetti et al., 2020), but also for infec- tion and atherosclerosis prevention, and wound healing (Żółkiewicz et al., 2020). PREBIOTICS VS PROBIOTICS VS POSTBIOTICS: WHAT IS THE DIFFERENCE? Prebiotics are food compounds that promote and support the growth and activity of beneficial gut
microorganisms. Probiotics, also known as ‘live biotherapeutics’, contain entire live microorgan- isms (such as bacteria and/or yeast). When they are applied in adequate amounts, they can help in balancing gut microbiota and consequently bring many health benefits including disease prevention and treatment of certain conditions. As the un- derstanding of probiotics and their mechanisms have developed it has become evident that many of their benefits are derived from their byproducts (secretions and internal compounds). These relat- ed compounds have now been defined as a sepa- rate biotic therapy – postbiotics.
POSTBIOTICS AND THEIR MICROBIAL PRODUCERS
Postbiotics are a highly varied array of compounds. They encompass microbial products and compo- nents such as short-chain fatty acids (SCFAs), mi- crobial fractions, functional proteins and enzymes, secreted and/or extracellular polysaccharides (EPS), cell lysates, teichoic and lipoteichoic acids, and peptidoglycan-derived muropeptides (Valle- jo-Cordoba et al., 2020).
Table 1 provides an overview of the main groups of postbiotics studied to date and their microbial producers. Further to these, bacte- riocins are receiving ever greater attention as they hold the potential to act as alternatives to antibiotics. Bacteriocins are complex peptides and proteins produced by bacteria capable of forming pores in the membranes of other bac- teria, inhibiting microbial cell wall synthesis. There are several classes of bacteriocins. In particular, nisins (lantibiotics) are small proteo- lytic and heat-resistant peptides with potent antimicrobial properties capable of inhibiting the growth of emerging pathobionts, including Staphylococcus aureus, Cutibacterium acnes, Mycobacterium smegmatis, Bacillus, Clostridi- um, Enterococcus, Mycobacterium, and Strep- tococcus strains (Vera-Santander et al., 2022). This bacteriocin is predominantly produced by Lactococcus lactis subsp. lactis and is approved by the FDA as a Generally Recognized as Safe Additive (“GRAS”) (Makhal et al., 2015).
al preparations in commercial products.
Postbiotics, compared to probiotics are more stable, have a better stability over time and better shelf-life, all of which significantly help with handling, transportation, and storage (Dunand et al., 2019). Consequently, postbi- otics can serve as an excellent alternative for live probiotics, since they do not require strict storage or transportation conditions, such as a cold chain. Postbiotics are found natu- rally in many fermented foods. However, the quantity present may not be sufficient to in- duce tangible physiological responses. While postbiotics hold great potential for addition to functional foods, improved scalable produc- tion techniques need to be developed first. Once consumed, postbiotics can be easily ab- sorbed and metabolized by the human body, which allow them to trigger several biological responses within tissues and organs that can further benefit the consumer. To ensure the op- timal effectiveness of postbiotic preparations, several technological aspects related to post- biotic production should be considered, such as growth medium, either in the microbial feed or a selective culture medium (e.g., MRS broth) and culture growth conditions (e.g., tempera- ture, pH, substrates, and water).
POSTBIOTIC PRODUCT APPLICATIONS
Postbiotics, similar to probiotics can be in- corporated into dietary supplements or food products, with an important difference, that postbiotics have demonstrated certain techno- logical advantages over the use of live microbi-
Table 1. Examples of postbiotics, as microbial-derived metabolites and their properties. Adopted from Puccetti et al., 2020. Initial
substrate utilized by microbes
Bacteria producers Postbiotic
Health properties
Short Chain Fatty Acids (SCFAs)
Fermentation of fibre/ carbohydrate metabolism
Bacteroidetes, Firmicutes
Propionate, Acetate, Butyrate
Preserve mucosal immunity; Enhance the regulatory function of Tregs in the intestine; Enhance the protection against infections; Suppression of pro- inflammatory cytokines and nitric oxide in neutrophils Increase protection from pathogenic infections by inducing IL-22 secretion and production of antimicrobial peptides; Enhancement of epithelial barriers;
Indole and Indole derivatives
Dietary Tryptophan (microbial origin)
5-hydroxy-tryptophan Tryptamine Indoleacetic acid 3-methylindole carboxaldehyde Indole-3-sulfate Indole propionic acid 3-indolelactic acid (Skatole) 3-indole
Firmicutes, Lactobacillus, Clostridium, Bacteroides
Secondary bile acids
Bile acids
Deoxycholic and lithocholic acid
Regulation of bacterial growth Inhibit induction of pro- inflammatory responses
Bacteroides, Bifidobacterium, Clostridium, Lactobacillus, Eubacterium
Polyamines
Nitrogenous compound
Putrescine, Spermidine, spermine
Established role in the regulation of growth and differentiation of all cell types; Can influence on cell proliferation rate; Implicated in wound healing Prevention against aberrant DNA methylation; Suppression of colonic inflammation; Maintaining redox homeostasis; Nucleotide metabolism
Escherichia Coli, Enterococcus faecalis, Bifidium
bacterium, Bacteroides
Amine oxides Folate, riboflavin
Vitamins
Bacillus subtilis Escherichia coli. Lactococcus lactis, Lactobacillus gasseri, Lactobacillus reuteri, Bifidobacterium adolescentis
Also, the inactivation technique should be care- fully selected between, for example, conventional (pasteurization or sterilization), physical technol- ogies (ultrasound, UV, high pressures, or irradia- tion) or separation (centrifugation followed by op- tional filtration) techniques. In the final stage, the method of postbiotic sterilization and incorpora- tion into the final food product or dietary supple- ment should be selected, depending on the food matrix, either as a liquid or solid (Vera-Santander et al., 2022). In addition, the benefits of adding postbiotics to foods, go beyond their benefits to human health, helping to improve food safety. This includes the preservation of dairy, meat, vegetable, and bak- ery products, through the presence of antimicro- bial compounds such as organic acids and/or bac- teriocins, mostly derived from lactic acid bacteria (Vera-Santander et al., 2022). For food production, the most used postbiotics include metabolites of probiotic strains of Lac- tobacillus and Bifidobacterium , that are valued by the dairy industry because of EPS production, which help to control over the rheological charac-
teristics of fermented dairy products and lowers their moisture content (Behare et al., 2009). Also, postbiotics derived from Lactobacillus plantarum demonstrated efficacy as a bio-preservatives as they can extend the shelf life of soybeans (Rath- er et al., 2013). Another novel approach involves increasing vitamin B and decreasing toxic com- ponents during probiotic-induced fermentation (Thorakkattu et al., 2022). For pharmaceutical applications, many postbi- otics, despite promising results demonstrated in the experimental research, have not reached clinical trials yet. Some of the remarkable discov- eries in this area include biosurfactants produced by L. gasseri with antibiofilm capacity against methicillin-resistant S. aureus (MRSA); as well as heat-stabilized L. acidophilus containing medica- tion called Lacteól Fort (Laboratoire du Lacteól du docteur Boucard, France), which was clinically effective in the treatment of acute diarrhoea and IBS by randomized controlled trials. Interestingly, incorporation of specific postbiotics, like those derived heat-killed Lactobacillus acidophilus LB and L. paracasei CBA L74 into infant formulas and fermented foods in early life, may help treat
paediatric diarrhoea and prevent common in- fectious diseases among young children (Malagón-Rojas et al., 2020). CLINICAL IMPLICATIONS AND METHODS To date, research evidence supports postbiotics’ potential as alternative agents, which may serve as safer options when compared to their parent live cells, and therefore can be applied as prom- ising compounds in the health and food industry (Rad et al., 2020). There is significant potential for the addition of postbiotics to food and health products to bring health benefits to a substantial portion of the population, including those suffering from the certain disease conditions, where they could play a meaningful therapeutic role. However, the suc- cess of postbiotics can depend on a variety of fac- tors, most of which are interrelated. For example, the postbiotic ability to induce a health effect on the individual may be fuelled by a variety of differ- ent processes or pathways, most of which remain unknown or yet unresearched . Also, postbiotics can consist of a complex mixture of bioactive com- ponents, in which characterisation can be limited
by current technologies. To be able to ensure that a commercial postbiotic product retains its prop- erties and other required health-promoting attri- butes effectively, it is crucial to understand the active molecules bringing the beneficial effects to the consumer. Investigations, including pre-clini- cal and clinical testing, need to be carried out in order to identify and isolate the safest and most functional strains responsible for production of the bioactive. Further studies are then needed to determine the optimum target population, the ideal effective dose, and the most efficient form of administration. To date, the research design for studies focusing on postbiotics has provided a great challenge for commercialization of these products (Thorakkattu et al., 2022). To date, no regulatory authorities, have devel- oped a postbiotic concept or framework that is particular to foods or dietary supplements that include postbiotics. For example, the European Food Safety Authority (EFSA) help to regulate the standards for food and are updated on a regular basis; while the European Pharmacopoeia pro- vides defined guidelines that specify maximum
permissible amounts of live microorganisms for pharmaceutical preparations and medicinal prod- ucts (01/2011:50104). Despite this lack of specific European regulation, many postbiotics (as well as probiotics, prebiotics, synbiotics) are still being advertised or licensed as immune-stimulating substances (Yin et al., 2018). On the other hand, the Food and Drug Adminis- tration (FDA) in the USA has no recommendations focused on postbiotics, and their use refer to the rules that apply to the individual regulatory catego- ry chosen for a product in development, meaning that the intended usage, safety, and efficacy of the probiotic-product must all fulfil the requirements for the relevant regulatory category (Thorakkattu et al., 2022). Evidence supporting postbiotic utility in the food and pharmaceutical industries is provided by an increasing number of both in vitro and in vivo studies, of which the focus is on postbiotic for- mulations produced from different Lactobacillus and Bifidobacterium strains and, to a lesser extent, from Saccharomyces species. CURRENT CLINICAL TRENDS IN POSTBIOTIC RESEARCH
In vitro investigations (e.g., cell lines and test- tube assays) help with identifying the bioactives in the postbiotic mixtures, while confirming their potential antimicrobial, anti-inflammatory, immu- nomodulatory, anti-proliferative and antioxidant properties. The exact mechanisms and proposed benefits are then tested in in vivo systems that employ the use of experimental animal models (e.g., rats, mice, hamsters). In those studies, the animals frequently receive a dietary intervention with the postbiotic at a dose calculated per body weight, helping to mimic a human real-case sce- nario. The intervention is then compared with an- imals receiving a control diet with no postbiotic (Cuevas-González et al., 2020). Once the postbiotic’s clinical capabilities in im- proving health outcomes are confirmed in an ani- mal model, the preparation can be further studied in humans. Of note, the efficacy found in animal studies may not translate to humans. Human stud- ies, or clinical studies, are primarily focused on confirming the suitability and efficacy of the post- biotics based on evidence obtained in the previous in vitro and in vivo studies. Clinical studies investi- gating postbiotics, similar to animal experiments,
can vary broadly in terms of targeted popula- tion and health outcomes. However, thus far, most of them have aimed to assess the postbi- otic effects on immune function (e.g., cytokine levels, immune cell activity/counts, resistance to infection), intestinal physiology, behaviour (e.g., under chronic or prolonged stress sit- uations), cardiometabolic markers, related to cardiovascular and metabolic health (Cue- vas-González et al., 2020). To date, there are 17 clinical studies registered in the FDA Clinical Trials Database (clinicaltri- als.gov) with the keyword “postbiotics”. Of these, eight studies are investigating postbiot- ic interventions (Table 2). Most of these were designed to evaluate dietary intervention with
postbiotics, usually derived from heat-treated probiotic bacteria, sometimes added with mul- tivitamins or vitamin D. These trials have been both open-label studies, as well as randomized control trials with double, triple or quadruple blinding. Interestingly, so far, there has only been one registered dose-dependent study – a study evaluating the preventive potential of polysaccharide extract of heat killed Bifidobac- terium breve in older adults. In addition, post- biotic trials have involved healthy individuals (infants, older adults) as well as patient groups with conditions such as obesity, type 2 diabe- tes, macular degradation, and allergic rhinitis. The study durations ranged from 3 weeks to 12 months, with an average follow up period of 4 weeks.
CLINICAL TRIALS PROCESS
Trial Design & Regulation
Participant Recruitment
Trial Conduct & Analysis
Trial Report & Outreach
CLINICAL TRIALS SUMMARY
Table 2. Summary of the most recently registered clinical trials investigating postbiotc interventions. Participants N Study design Intervention Status
Duration (months)
Patients with Geographic Atrophy Age-Related Macular Degeneration Children with obesity
10 Open label study with dietary intervention 30 Open label study with dietary intervention; phase 4 60 Open label study with dietary intervention 31 Open label study with dietary intervention
Postbiotic with added multivitamin supplement
12
Active, not recruiting
4
Unknown status
Postbiotic Lactobacillus paracasei CNCM I-5220 with added vitamin D3 Postbiotic (cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023 ) Cow’s milk based infant formula containing prebiotics, probiotics and postbiotics
Patients aged between 18 and 70 years of age with type 2 diabetes
3 months (intervention) + 3 months of follow up
Recruiting
Singleton infants aged between 14 and 84 days of age with a gestational age at birth of ≥37 weeks and ≤41 weeks
1
Completed
Patients with macular degeneration
48 A randomized parallel assignment
Postbiotic added with vitamins
12
Recruiting
with quadruple masking study with dietary intervention
Singleton infants aged between 0 days to 17 weeks and with a gestational age at birth of ≥37 weeks and ≤41 weeks
279 A randomised, controlled, double-blind,
Infant formula with prebiotics and postbiotics
17
Completed
parallel study with triple masking
Older healthy adults (females) aged between 50 and 65 years of age
30 Double blinded, placebo controlled, randomised dose response study with triple masking
3
Active, not recruiting
Postbiotic Heat killed and purified Bifidobacterium breve polysaccharide-based extract
POSTBIOTICS FUTURE OPPORTUNITIES FOR THE INDUSTRY
ucts Improved microencapsulation techniques would allow postbiotics to be better incorporat- ed into a wider array of food and pharmaceutical preparations. The emerging trend is to use postbiotics, main- ly antimicrobial peptides and bacteriocins to im- prove food safety through development of bio- active and edible packaging, the prevention and control of biofilms in food machinery; and the reduction and degradation of contaminants, such as biogenic amines, pesticides, and mycotoxins. Nevertheless, this area needs to be further inves- tigated, as certain interaction between postbiot- ics and food components could negatively impact on the product taste, odour or appearance (Ve- ra-Santander et al., 2022). Despite the many potential uses for postbiotics in the food and health industries, important safety and regulatory aspects still need to be addressed. Large-scale manufacturing processes for the pro- duction of postbiotics at industrial level need to be developed, as well as new, more efficient tech- niques for the discovery, isolation and charac- terization of novel postbiotics in order to ensure product quality and effectiveness.
Foods enriched with postbiotics can provide sev- eral health benefits such as the regulation of the intestinal microbiota, mitigating of gastrointesti- nal symptoms and heart diseases, while poten- tially providing antioxidant, , anti-inflammatory, psychobiotic, anti-obesity, and antiviral capaci- ties. Although studies to date have characterised nu- merous bioactive postbiotic compounds that have been associated with health-promoting effects in in vivo and clinical studies, the mech- anisms of action largely remain partially or com- pletely undefined. Future studies need to focus on determining mechanistic pathways and fully document clinical health outcomes. More evi- dence is needed, particularly from robust clinical studies, if health claims are to be sought. Further- more, more research is needed regarding micro- encapsulation and postbiotic incorporation into functional foods. To date, postbiotics have mostly been used in the applica- tion of fermented foods, especially in dairy prod-
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Bibliography
01/2011:50104. 5.1.4. Microbiological Quality of Non-Sterile Products for Pharmaceutical Use. Available online: https://www.medicinalgenomics. com/wp-content/uploads/2013/04/CFU_Toler- ance_European.pdf (accessed on 22 March 2023). Aggarwal S, Sabharwal V, Kaushik P, Joshi A, Aay- ushi A, Suri M. Postbiotics: From emerging concept to application. Frontiers in Sustainable Food Sys- tems, 2022, 6. DOI=10.3389/fsufs.2022.887642 Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, Ma- ta-Haro V, González-Córdova AF, Vallejo-Cordoba B, Hernández-Mendoza A. Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology. 2018 May 1;75:105-14. Ahmad Rather I, Seo BJ, Rejish Kumar VJ, Choi UH, Choi KH, Lim JH, Park YH. Isolation and character- ization of a proteinaceous antifungal compound from Lactobacillus plantarum YML007 and its ap- plication as a food preservative. Letters in Applied Microbiology. 2013 Jul 1;57(1):69-76.
Behare P, Singh R, Singh RP. Exopolysaccharide-pro- ducing mesophilic lactic cultures for preparation of fat-free Dahi–an Indian fermented milk. Journal of dairy research. 2009 Feb;76(1):90-7. Beltrán-Barrientos LM, González-Córdova AF, Hernández-Mendoza A, Torres-Inguanzo EH, Asti- azarán-García H, Esparza-Romero J, Vallejo-Cordo- ba B. Randomized double-blind controlled clinical trial of the blood pressure–lowering effect of fer- mented milk with Lactococcus lactis: A pilot study. Journal of Dairy Science. 2018 Apr 1;101(4):2819- 25.
Cuevas-González PF, Liceaga AM, Aguilar-Toalá JE. Postbiotics and paraprobiotics: From concepts to applications. Food Res Int. 2020 Oct;136:109502.
Deptula P, Chamlagain B, Edelmann M, Sangsuwan P, Nyman TA, Savijoki K, Piironen V, Varmanen P. Food-like growth conditions support production of active vitamin B12 by Propionibacterium freuden- reichii 2067 without DMBI, the lower ligand base, or cobalt supplementation. Frontiers in Microbiol- ogy. 2017 Mar 8;8:368. Dunand E, Burns P, Binetti A, Bergamini C, Peralta GH, Forzani L, Reinheimer J, Vinderola G. Postbi- otics produced at laboratory and industrial level as potential functional food ingredients with the capacity to protect mice against Salmonella in- fection. Journal of applied microbiology. 2019 Jul 1;127(1):219-29.
Makhal S, Kanawjia SK, Giri A. Effect of microG- ARD on keeping quality of direct acidified Cottage cheese. Journal of food science and technology. 2015 Feb;52:936-43. Nishida K, Sawada D, Kawai T, Kuwano Y, Fujiwara S, Rokutan K. Para‐psychobiotic Lactobacillus gas- seri CP2305 ameliorates stress‐related symptoms and sleep quality. Journal of Applied Microbiolo- gy. 2017 Dec 1;123(6):1561-70.Ma L, Tu H, Chen T. Postbiotics in Human Health: A Narrative Review. Nutrients. 2023 Jan 6;15(2):291. Puccetti M, Xiroudaki S, Ricci M, Giovagnoli S. Postbiotic-Enabled Targeting of the Host-Micro- biota-Pathogen Interface: Hints of Antibiotic De- cline? Pharmaceutics. 2020 Jul 4;12(7):624. Rad AH, Abbasi A, Kafil HS, Ganbarov K. Poten- tial Pharmaceutical and Food Applications of Postbiotics: A Review. Curr Pharm Biotechnol. 2020;21(15):1576-1587.
European Medicines Agency (EMA). Bacterial Ly- sates-Containing Medicinal Products for Respira- tory Conditions.
Hossain MS, Tajima A, Kotoura S, Katafuchi T. Oral ingestion of plasmalogens can attenuate the LPS-induced memory loss and microglial activa- tion. Biochemical and biophysical research com- munications. 2018 Feb 19;496(4):1033-9.
Schönfeld P, Wojtczak L. Short-and medium-chain fatty acids in energy metabolism: the cellular perspective. Journal of lipid research. 2016 Jun 1;57(6):943-54.
nr.2020.06.001
Wallner S, Schmitz G. Plasmalogens the neglected regulatory and scavenging lipid species. Chemistry and physics of lipids. 2011 Sep 1;164(6):573-89.
Sharma N, Kang DK, Paik HD, Park YS. Beyond pro- biotics: a narrative review on an era of revolution. Food Sci Biotechnol. 2022 Nov 30;32(4):413-421.
Yang R, Qian L. Research on Gut Microbiota-Derived Secondary Bile Acids in Cancer Progression. Integr Cancer Ther. 2022 Jan-Dec;21:15347354221114100.
Thorakkattu P, Khanashyam AC, Shah K, Babu KS, Mundanat AS, Deliephan A, Deokar GS, Santiva- rangkna C, Nirmal NP. Postbiotics: Current trends in food and Pharmaceutical industry. Foods. 2022 Oct 5;11(19):3094. Vera-Santander VE, Hernández-Figueroa RH, Jiménez-Munguía MT, Mani-López E, López-Malo A. Health Benefits of Consuming Foods with Bacteri- al Probiotics, Postbiotics, and Their Metabolites: A Review. Molecules. 2023 Jan 27;28(3):1230. Vallejo-Cordoba, B. et al. (2020) ‘Postbiotics and paraprobiotics: A review of current evidence and emerging trends’, Advances in Food and Nu- trition Research, pp.1-34. Doi:10.1016/bs.af-
Yin J, Xu B, Zeng X, Shen K. Broncho-Vaxom in pe- diatric recurrent respiratory tract infections: a sys- tematic review and meta-analysis. International immunopharmacology. 2018 Jan 1;54:198-209.
Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics—a step beyond pre-and probiotics. Nu- trients. 2020 Aug;12(8):2189.
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