June/July 2022 Issue

Postbiotics: The Myths and Facts About Postbiotics
By Carrie Dennett, MPH, RDN, CD
Today’s Dietitian
Vol. 24, No. 5, P. 22

No, they don’t come from our gut or from fermented foods.

As any dietitian knows, the internet can be a source of both information and misinformation—even from experts. For example, when searching for information on postbiotics, the first page of search results may include incorrect statements from doctors at major institutions saying that postbiotics are “byproducts of the fermentation process carried out by probiotics in the intestine” or “the waste left behind after your body digests both prebiotics and probiotics.” RDs also may see misleading headlines, such as “The Key to Reaping the Benefit of Postbiotics From Foods” or claims that fermented foods contain postbiotics.

“It is an unfortunate fact that imminently qualified physicians are not necessarily knowledgeable in the ‘-biotics’ space,” says Mary Ellen Sanders, PhD, executive science officer of the International Scientific Association for Probiotics and Prebiotics (ISAPP). “For example, many high-profile institutions claim that the best way to get probiotics is from fermented foods. Of course, this is not true. Fermented foods, for many reasons, can fall short of delivering probiotics. But still this error is propagated by many ‘experts.’”

So then, what are postbiotics? In 2021, ISAPP, a nonprofit collaboration of scientists, published a consensus definition, stating that a postbiotic is “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.” Postbiotics may include whole microbial cells and/ or components of the cells—for example, organelles, cell wall components, or extracellular membrane vesicles—as long as they’ve been deliberately inactivated.1,2

Sanders says metabolites produced in the gut or in a fermented food (in situ) don’t fit that definition. Neither do “purified” metabolites isolated from the microorganisms that produced them, such as butyrate, lactic acid, or antibiotics. “Now, a postbiotic can certainly contain bacterial fermentation products as part of the preparation, and surely many do,” she says. “For example, there are infant formula products that are fermented milks that are pasteurized and contain the dead fermentation bacteria as well as their metabolic products.”

Some fermented foods—especially those that are pasteurized or baked, such as soy sauce and sourdough bread—may contain many microorganisms that are nonviable at the time of consumption, but this doesn’t meet the postbiotic criteria.1 “Fermentation in bread or yogurt is not necessarily random, and may result in predictable metabolites,” Sanders says. “But for postbiotics, the focus is not on the metabolites but on the dead/inactivated/ inanimate cells.” She also emphasizes that a postbiotic needs to be made in a controlled, repeatable manner. This allows for consistency between batches and also allows the product to be tested in research studies.

Producing Postbiotics
Postbiotics are prepared from live microbes through a process that inactivates the cells, often using exposure to heat, high pressure, or oxygen. Production starts with accurate identification of the starter microorganism and a description of how it’s inactivated, along with a description and quantification of the final postbiotic composition. Different inactivation procedures could result in a different postbiotic composition—even when the same starting microorganism is used—which could have different health effects.1,3

For example, one postbiotic developed to prevent and treat recurrent infections of the respiratory tract started with 21 different strains of pathogenic bacteria grown in individual batches. They were then inactivated with heat, harvested, subjected to alkaline lysis—to isolate the desired components—and purified.1,4

In a press release, Seppo Salminen, PhD, MSc, MS, lead author on ISAPP’s consensus definition of postbiotics and a professor at and director of the Functional Foods Forum at the University of Turku in Finland, said, “With this definition of postbiotics, we wanted to acknowledge that different live microorganisms respond to different methods of inactivation. Furthermore, we used the word ‘inanimate’ in favor of words such as ‘killed’ or ‘inert’ because the latter could suggest the products had no biological activity.”

Overview of -Biotics
While it’s important to understand the correct definition of postbiotics, it’s just as vital to understand the fundamentals of probiotics and even prebiotics. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.”5 Probiotics can be delivered through dietary supplements or added to foods that aren’t already fermented, such as fruit juice. These “probiotic foods” are different from probiotic fermented foods, such as yogurt or fermented plant-based or dairy milks. Probiotics, probiotic foods, and probiotic fermented foods all must have documented health benefits, contain microbes that are defined down to the strain level and are alive at the time of consumption at levels that provide benefit, and have available genome sequencing for the microbes.

A prebiotic is a “substrate that is selectively utilized by host microorganisms conferring a health benefit.” In other words, a prebiotic is food for beneficial microbes that are already residing in the host. Examples of prebiotics include inulin, galactooligosaccharides, and fructooligosaccharides.6 A synbiotic is “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.”7

A postbiotic doesn’t need to be derived from probiotic microorganisms, which means that the live precursor microorganism itself doesn’t have to have a demonstrated health benefit before it’s used to create a postbiotic. However, because postbiotics are inanimate, any bioactive molecules must be synthesized by the starting microorganism before it’s inactivated in sufficient amounts to have a health benefit. Most final postbiotic products won’t contain any viable cells, but there could be a few survivors depending on how they were inactivated. As a result, postbiotics are more stable than probiotics, which may make them more suitable for areas of the world where transporting and storing live microorganisms at appropriately cool temperatures is challenging. Postbiotics also may have broader application for use in foods.1

“The concept of postbiotics, consistent with all the other ‘-biotics,’ relates to a product to be applied or consumed by a host,” Sanders says. “None of the -biotics refers to substances produced in situ. Instead, they are substances that can be used to help promote health or manage disease, depending on their regulatory category.”

Potential Health Benefits of Postbiotics
Because different postbiotic preparations contain different mixtures of components, they may have health effects via diverse mechanisms. Potential health effects include beneficial modulation of the gut microbiota, immune responses, and metabolism, as well as production of molecules that can act on the enteric (gut) and central nervous systems.1

Postbiotics have been available for more than 100 years in Japan, and fermented infant formulas with postbiotics are commercially available in South America, the Middle East, and some European countries.1,8 However, data from human clinical trials are limited and of variable quality. In adults, there’s evidence that oral preparations of inactivated lactic acid bacteria can eradicate Helicobacter pylori infection, reduce symptoms in patients with diarrhea-predominant irritable bowel syndrome or just chronic diarrhea, and reduce the effects of chronic stress.9-12 A randomized controlled trial of inactivated Bifidobacterium bifidum MIMBb75, given orally, found that it alleviated symptoms of irritable bowel syndrome.13 In children, there’s conflicting evidence supporting inactivated Lactobacillus acidophilus LB for reducing duration of diarrhea during hospitalization. Evidence supporting the benefits of fermented infant formulas over standard formulas is lacking.1

“As with probiotics, you must be careful not to generalize about the whole category,” Sanders says. “Health benefits are specific to specific preparations.”

Counseling Strategies for RDs
Many supplement companies are pushing postbiotic products with claims that include digestive health, improved immune function, and weight loss. Some even include prebiotics, probiotics, and postbiotics in one pill. Should dietitians be recommending them to their clients and patients? According to current evidence, the answer is probably not.

Sanders says a product worth buying would have been subjected to human clinical trials, and those trials would demonstrate a health benefit. “Before buying a product, ask the company for documentation of a health benefit,” Sanders says. “If that benefit is what you are looking for, then there would be reason to buy it.”

Many postbiotic supplements are marketed toward people who generally are already healthy and perhaps interested in optimizing wellness. As with probiotics, Sanders says that establishing postbiotic health benefits for healthy people is challenging, largely because such studies are difficult to do. “How do you improve the health of a healthy person? You may be able to reduce the risk of disease, but those studies require a large number of subjects and a reasonable effect size,” she says. “Any company marketing a product claiming to help healthy people should be able to provide evidence of controlled human research documenting the benefit.”

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times, owner of Nutrition by Carrie, and author of Healthy for Your Life: A Holistic Guide to Optimal Wellness.


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;18:649-667.

2. Vinderola G. Bacterial vesicles: emerging potential postbiotics. ISAPP Science Blog website. https://isappscience.org/bacterial-vesicles-emerging-potential-postbiotics/. Published July 22, 2021.

3. Vinderola G. Should the concept of postbiotics make us see probiotics from a new perspective? ISAPP Science Blog website. https://isappscience.org/should-the-concept-of-postbiotics-make-us-see-probiotics-from-a-new-perspective/. Published October 5, 2021.

4. Huber M, Mossmann H, Bessler WG. Th1-orientated immunological properties of the bacterial extract OM-85-BV. Eur J Med Res. 2005;10(5):209-217.

5. 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.

6. 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.

7. 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.

8. Behind the publication: understanding ISAPP’s new scientific consensus definition of postbiotics. ISAPP Science Blog website. https://isappscience.org/behind-the-publication-understanding-isapps-new-scientific-consensus-definition-of-postbiotics/. Published May 5, 2021.

9. Canducci F, Armuzzi A, Cremonini F, et al. A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol Ther. 2000;14(12):1625-1629.

10. 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.

11. 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.

12. 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):1859.

13. 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.