"20 FAQs about Postbiotics (Part 2)" - Clinical Research and Usage of Postbiotics

 

V. Mechanisms and Clinical Research

 

16 Postbiotics andProbioticshave similar beneficial effects, but they do not rely on the activity of bacteria. So what is the mechanism by which postbiotics exert their effects?
 

According to existing research, the ISAPP consensus summarizes the mechanisms by which postbiotics exert their effects as follows:

A. Beneficial modulation of the microbiome.

B. Enhancement of epithelial barrier function.

C. Modulation of immune responses.

D. Regulation of systemic metabolism.

E. Effects on the nervous system.

 

17 What diseases can postbiotics be used to prevent and treat, and what is the current state of clinical research?

 

Currently, research on postbiotics is still in its early stages, with limited human study data. The postbiotics being explored mainly include inactivated Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium, with the diseases studied primarily being gastrointestinal diseases, obesity, skin allergies, and stress management.

(1) Gastrointestinal diseases: Several clinical studies have explored the effects of postbiotics on improving irritable bowel syndrome (IBS). For example, in 2020, a multicenter, randomized, double-blind, controlled clinical trial published in The Lancet Gastroenterology and Hepatology found that taking inactivated Bifidobacterium MIMBb75 once daily significantly improved IBS symptoms.

Additionally, some studies have explored the effects of postbiotics on diarrhea. For instance, a 2014 meta-analysis showed that heat-inactivated Lactobacillus acidophilus LB could shorten the duration of diarrhea in hospitalized children. Although multiple studies support the effects of various postbiotics in alleviating diarrhea, the mechanisms involved remain unclear, and there are contradictions among some trial results, necessitating further investigation.

(2) Obesity:Obesityhas become a global issue. A randomized, double-blind, placebo-controlled trial published in Nature Medicine in 2019 indicated that inactivated Akkermansia could improve the metabolism of obese individuals, while the benefits of supplementing with active Akkermansia were not significant. Additionally, it is worth mentioning that although not a clinical study, some mouse studies have shown that supplementing with inactivated Akkermansia can help improve weight loss in obese mice.

(3) Skin allergies: There is currently no conclusion on whether postbiotics can improve skin allergy issues. An article published in 2003 indicated that both inactivated and active Lactobacillus rhamnosus GG added to a deeply hydrolyzed whey formula could improve infant eczema. However, a 2020 RCT showed that cell lysates (including heat-inactivated Escherichia coli and Enterococcus faecalis) could not improve skin allergy issues in children.

(4) Stress management: Some studies have explored theeffects of postbioticson alleviating stress. Two human studies indicated that heat-inactivated Lactobacillus casei CP2305 could significantly improve stress and reduce anxiety, although larger-scale trials are needed for further confirmation.

Additionally, some studies have explored the effects of postbiotics in preventing and treating Helicobacter pylori infections, colds, and other diseases. For example, a 2013 study indicated that Lactobacillus reuteri DSMZ 17648 could reduce the burden of Helicobacter pylori in highly endemic populations.

Although previous clinical evidence regarding the use of postbiotics for disease prevention and treatment is very limited, it is believed that with ongoing research, more large-scale, high-quality, and rigorous trial data will support the efficacy of postbiotics.

 

VI. Regulation

 

18 What is the current regulatory status regarding postbiotic-related raw materials and products?

 

Currently, no regulatory agency has proposed a definition for foods or dietary supplements containing postbiotics. However, some agencies have proposed regulatory requirements for postbiotic preparations used for medical or pharmaceutical purposes. For instance, in 2019, the EU issued relevant documents for a bacterial lysate drug used to prevent recurrent respiratory infections.

The specific regulatory situation for postbiotics in different countries is as follows:

In Japan, the use of postbiotics has a history of over 100 years, with inactivated lactic acid bacteria or bifidobacteria commonly added to various foods. Most foods containing inactivated microorganisms do not have health claims, while postbiotic foods with health claims mainly apply based on the FFC (Food With Functional Claims) declaration system introduced in Japan in 2015, which requires submission of scientific evidence consistent with the claimed function to the Japanese Consumer Affairs Agency 60 days before market launch.

Although the EU has not issued specific regulations for postbiotics, some postbiotics have been marketed or regulated as immune stimulants. Additionally, the EU has proposed a safety qualification certification (QPS) management concept for effective regulation of microorganisms used in food and feed, and has established a QPS biological agent list (regularly updated), which may provide an opportunity for safety assessment of microorganisms producing postbiotics.

In the United States, the FDA does not specifically evaluate or inspect postbiotics, but since postbiotics can be developed under different regulatory categories, the FDA may choose specific regulatory category standards based on the intended use, safety, and efficacy of postbiotics.

China has not yet issued standards for postbiotics, but it is currently formulating group standards for postbiotic preparations.

In fact, in most cases, food development precedes regulation. Although there are no clear international regulatory standards for postbiotics, in some countries, postbiotics have been incorporated into national regulatory regulations, and their products have entered the public eye. In summary, research on the definition, mechanisms, efficacy, and safety of postbiotics will provide practical assessment standards for producers and regulatory agencies.

 

VII. Dosage

 

19 How should the dosage of postbiotics be assessed for better animal and clinical experiments?

 

National/international standards regarding recommended intake levels for probiotics are relatively mature, but research on postbiotics is still in the preliminary exploration stage, and no relevant standards have been issued to regulate/recommend their intake levels.

Based on existing population/clinical trials on postbiotics, studies focusing on inactivated bacterial bodies indicate the dosage of dead bacteria. Due to the diverse and variable nature of metabolic products, current research focusing on metabolic products has not yet specified exact dosages. In the future, collaboration between academia and industry is needed to characterize the content range of the main products in postbiotic series products.

 

8. Usage Recommendations

 

20. How should consumers choose postbiotic products?
 

With the rapid development of postbiotic research, related products are beginning to increase in the market, but it is also inevitable that there will be a mix of good and bad.

We first recommend that consumers clarify their needs, conduct detailed product research, and choose products that meet their needs; secondly, consumers should pay attention to the includedfermented strains, determine whether the strains have a clear source and whether they are safe and reliable (for example, free from transferable resistance genes, not carrying virulence factors, etc.); thirdly, consumers should pay attention to whether postbiotic products have relevant efficacy testing support; finally, consumers should pay attention to the unsuitable populations for the product to determine safety.

 

References:

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.

2. Aguilar-Toalá JE, Arioli S, Behare P, et al. Postbiotics—When simplification fails to clarify. Nature Reviews Gastroenterology & Hepatology. 2021;18(11):825-826.

3. Salminen S, Collado MC, Endo A, et al. Reply to: Postbiotics — when simplification fails to clarify. Nature Reviews Gastroenterology & Hepatology. 2021;18(11):827-828.

4. Rad AH, Aghebati-Maleki L, Kafil HS, Abbasi A. Molecular mechanisms of postbiotics in colorectal cancer prevention and treatment. Crit Rev Food Sci Nutr. 2021;61(11):1787-1803.

5. Aguilar-Toalá J, Garcia-Varela R, Garcia H, et al. Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology. 2018;75:105-114.

6. Faintuch J, Faintuch S. Microbiome and metabolome in diagnosis, therapy, and other strategic applications. Academic Press; 2019.

7. Collado M, Vinderola G, Salminen S. Postbiotics: facts and open questions. A position paper on the need for a consensus definition. Beneficial microbes. 2019;10(7):711-719.

8. Johnson CN, Kogut MH, Genovese K, He H, Kazemi S, Arsenault RJ. Administration of a Postbiotic Causes Immunomodulatory Responses in Broiler Gut and Reduces Disease Pathogenesis Following Challenge. Microorganisms. 2019;7(8).

9. Wegh CAM, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int J Mol Sci. 2019;20(19).

10. 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.

11. 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.

12. 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.

13. Marco ML, Sanders ME, Ganzle 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.

14. Marco ML, Heeney D, Binda S, et al. Health benefits of fermented foods: microbiota and beyond. Curr Opin Biotechnol. 2017;44:94-102.

15. 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.

16. Champagne CP, da Cruz AG, Daga M. Strategies to improve the functionality of probiotics in supplements and foods. Current Opinion in Food Science. 2018;22:160-166.

17. Hartmann HA, Wilke T, Erdmann R. Efficacy of bacteriocin-containing cell-free culture supernatants from lactic acid bacteria to control Listeria monocytogenes in food. International Journal of Food Microbiology. 2011;146(2):192-199.

18. Garnier L, Mounier J, Lê S, et al. Development of antifungal ingredients for dairy products: From in vitro screening to pilot scale application. Food microbiology. 2019;81:97-107.

19. Chanos P, Mygind T. Co-culture-inducible bacteriocin production in lactic acid bacteria. Appl Microbiol Biotechnol. 2016;100(10):4297-4308.

20. Prado C, Santos W, Carvalho C, Moreira E, Costa O. Antimicrobial activity of lactic acid bacteria isolated from Brazilian dry fermented sausages against Listeria monocytogenes. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 2000;52:417-423.

21. Pahlow S, Meisel S, Cialla-May D, Weber K, Rosch P, Popp J. Isolation and identification of bacteria by means of Raman spectroscopy. Adv Drug Deliv Rev. 2015;89:105-120.

22. Kailasa SK, Koduru JR, Baek SH, Wu H-F, Hussain CM, Park TJ. Review on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the rapid screening of microbial species: A promising bioanalytical tool. Microchemical Journal. 2020;159:105387.

23. Losito I, Facchini L, Valentini A, Cataldi TR, Palmisano F. Fatty acidomics: Evaluation of the effects of thermal treatments on commercial mussels through an extended characterization of their free fatty acids by liquid chromatography–Fourier transform mass spectrometry. Food chemistry. 2018;255:309-322.

24. Ortolani TS, Pereira TS, Assumpcao MH, Vicentini FC, de Oliveira GG, Janegitz BC. Electrochemical sensing of purines guanine and adenine using single-walled carbon nanohorns and nanocellulose. Electrochimica Acta. 2019;298:893-900.

25. Aguilar-Toala JE, Hall FG, Urbizo-Reyes UC, et al. In Silico Prediction and In Vitro Assessment of Multifunctional Properties of Postbiotics Obtained From Two Probiotic Bacteria. Probiotics Antimicrob Proteins. 2020;12(2):608-622.

26. Fusieger A, Perin LM, Teixeira CG, de Carvalho AF, Nero LA. The ability of Lactococcus lactis subsp. lactis bv. diacetylactis strains in producing nisin. Antonie Van Leeuwenhoek. 2020;113(5):651-662.

27. Ali K, Mehmood MH, Iqbal MA, et al. Isolation and characterization of exopolysaccharide-producing strains of Lactobacillus bulgaricus from curd. Food Sci Nutr. 2019;7(4):1207-1213.

28. Ray S, Sherlock A, Wilken T, Woods T. Cell wall lysed probiotic tincture decreases immune response to pathogenic enteric bacteria and improves symptoms in autistic and immune compromised children. Explore. 2010;19(1):1-5.

29. Martinez-Rios V, Pedersen M, Pedrazzi M, Gkogka E, Smedsgaard J, Dalgaard P. Antimicrobial effect of nisin in processed cheese-Quantification of residual nisin by LC-MS/MS and development of new growth and growth boundary model for Listeria monocytogenes. International Journal of Food Microbiology. 2021;338:108952.

30. Roda A, Simoni P, Magliulo M, et al. A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon. World J Gastroenterol. 2007;13(7):1079-1084.

31. Grandclement C, Tannieres M, Morera S, Dessaux Y, Faure D. Quorum quenching: role in nature and applied developments. FEMS Microbiol Rev. 2016;40(1):86-116.

32. Sabahi S, Homayouni Rad A, Aghebati-Maleki L, et al. Postbiotics as the new frontier in food and pharmaceutical research. Critical Reviews in Food Science and Nutrition. 2022:1-28.

33. Sharieff W, Bhutta Z, Schauer C, Tomlinson G, Zlotkin S. Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan Sprinkles Diarrhoea Study. Archives of disease in childhood. 2006;91(7):573-579.

34. 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.

35. 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.

36. Depommier C, Van Hul M, Everard A, Delzenne NM, De Vos WM, Cani PD. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes. 2020;11(5):1231-1245.

37. Warda AK, Rea K, Fitzgerald P, et al. Heat-killed lactobacilli alter both microbiota composition and behaviour. Behav Brain Res. 2019;362:213-223.

38. Xiao SD, Zhang DZ, Lu H, et al. Multicenter, randomized, controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrhea. Adv Ther. 2003;20(5):253-260.

39. Kaila M, Isolauri E, Saxelin M, Arvilommi H, Vesikari T. Viable versus inactivated lactobacillus strain GG in acute rotavirus diarrhoea. Arch Dis Child. 1995;72(1):51-53.

40. Szajewska H, Ruszczynski M, Kolacek S. Meta-analysis shows limited evidence for using Lactobacillus acidophilus LB to treat acute gastroenteritis in children. Acta Paediatr. 2014;103(3):249-255.

41. Tarrerias AL, Costil V, Vicari F, et al. The effect of inactivated Lactobacillus LB fermented culture medium on symptom severity: observational investigation in 297 patients with diarrhea-predominant irritable bowel syndrome. Dig Dis. 2011;29(6):588-591.

42. Kirjavainen PV, Salminen SJ, Isolauri E. Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr. 2003;36(2):223-227.

43. Jeong K, Kim M, Jeon SA, Kim YH, Lee S. A randomized trial of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) for treating atopic dermatitis. Pediatr Allergy Immunol. 2020;31(7):783-792.

44. Nishida K, Sawada D, Kawai T, Kuwano Y, Fujiwara S, Rokutan K. Para-psychobiotic Lactobacillus gasseri CP2305 ameliorates stress-related symptoms and sleep quality. J Appl Microbiol. 2017;123(6):1561-1570.

45. Nishida K, Sawada D, Kuwano Y, Tanaka H, Rokutan K. Health Benefits of Lactobacillus gasseri CP2305 Tablets in Young Adults Exposed to Chronic Stress: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2019;11(8).

Source: Enthusiastic Intestinal Research Institute, authorized for reproduction.