Postbiotic Progress: Definitional clarity moves the postbiotic field forward

Nutritional Outlook, Volume 25, Issue 4

In May 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) formally defined what, operationally speaking, a postbiotic is. So what does this signal for the postbiotics market?

Postbiotics, both as a concept and as a marketable wellness technology, are hardly new to the biotics scene. But it took until May 2021 for a panel convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to release a consensus paper1 formally defining what, operationally speaking, a postbiotic is.

And when they did, biotics insiders gave a glad cry.

“Finally,” says Jacqueline Rizo, digital engagement and communications specialist, Stratum Nutrition (Carthage, MO), “there’s some clarity regarding what postbiotics are and how they can positively impact human health.”

Thanks to that clarity, these “preparations of inanimate microorganisms and/or their components that confer a health benefit on the host”—per the ISAPP definition—can officially join probiotics and prebiotics in a class of, per Rizo’s definition, “premier nutritional ingredients that provide the next level of support for the beneficial microorganisms that populate our bodies.”

How We Got Here

Rizo’s kept her eye on postbiotics for some time, and in so doing she’s seen their popularity grow even absent a “consistent industry understanding of how to define them,” she says.

In that absence, terms like ghost probiotics, zombie probiotics, paraprobiotics, and—yes—postbiotics arose, hinting, Rizo says, at “some vague entity that encompassed probiotics’ benefits, but without the constraints of shelf or gastric survival.”

Over time, the postbiotic moniker rose to the top, and in 2019, ISAPP gathered its experts in nutrition, microbial physiology, gastroenterology, pediatrics, food science, and microbiology to consider, as the panel wrote, “the scientific, commercial, and regulatory parameters encompassing this emerging term,” and thus to hammer out “a unified consensus definition of a postbiotic.”

And the rest, we now know, is history.

Clarity or Contention?

But that history bodes well for postbiotics’ future.

As Justin Green, PhD, director of scientific affairs, health technologies business, Cargill (Ankeny, IA), says, “Having an internationally recognized definition is an important step for the postbiotic category, especially as these emerging ingredients gain mainstream recognition.”

But not everyone in the biotics space is eager to recognize the definition.

Linda May-Zhang, PhD, research, science, and innovation officer, Blue California (Rancho Santa Margarita, CA), is among them. She argues that by limiting the postbiotic category to nonliving cells and cellular components that confer health benefits on the host, the ISAPP definition eschews earlier, less-formalized definitions that focused on “well-defined” metabolic byproducts of living gut bacteria—“often without bacterial cells in the composition,” she adds. It also ignoring the “large body of published studies” that regarded postbiotics those very metabolic byproducts.

Pointing out that parabiotics has long been the common term for the inactivated, nonviable, or dead cells that ISAPP now calls postbiotics, May-Zhang believes that to include these in a definition that simultaneously excludes microbial metabolites both causes “great confusion and disagreement within the scientific community” and “shifts the focus” of postbiotic innovation away from purified microbial metabolites toward “assessing the benefits of inanimate or nonviable cells.”

Setting the Stage

So those are the critiques. Even so, May-Zhang concedes that “whether one believes that postbiotic includes or excludes nonliving cells or microbial metabolites, the current ISAPP definition has certainly spurred attention to and engagement in this emerging category of biotics.”

And that, everyone can agree with. For example, Marta Tortajada Serra, vice president, science and technology, health and wellness, ADM (Chicago), believes that the definition has given product developers a standard for formulation and brands “the confidence to expand their portfolio of microbiome-supporting products.”

For consumers, she continues, the definition helps set reasonable expectations around product benefits “through more clearly defined information sharing,” while for regulators, she hopes it will “lead to additional clarity for guidelines as new solutions are developed in this space.”

Consumers Cluing In

Such guidelines couldn’t come soon enough, either, as interest in postbiotics “is at an all-time high,” Green observes, despite it being “a nascent category.”

Innova Market Insights has counted more than 75 postbiotic-related supplement, food, and beverage launches since 2019, with an additional 10 appearing in the pet food category. Meanwhile, Google searches for postbiotics have increased “exponentially,” Green says, with Lumina Intelligence tracking a rise of 1,300% in the last two years alone. “All of this suggests that consumers are actively seeking new health solutions, and that the momentum around postbiotics continues to increase,” Green concludes.

David Tetzlaf, marketing director at Blue California, agrees, adding that the Lumina findings “put the keyword postbiotic at a similar rank with more established search categories like cardiovascular health and immunity.”

Science Behind the Sensation

Which is actually a fitting parallel, given the relationship that postbiotics—like their pre- and probiotic counterparts—have to gut health and, by extension, to immunity.

“Postbiotics provide an entirely new arena for supporting the health of our own microbiome,” Rizo explains. “Most are marketed for digestive support, but that can be intertwined with immune support, since our intestinal microbiota play such critical roles in immune function.”

The science bears her out. For example, Rizo says that Stratum Nutrition’s LBiome postbiotic—which she describes as the heat-treated cellular biomass and fermentate of the human-derived bacterial species Limosilactobacillus fermentum and Lactobacillus delbrueckii ssp. Delbrueckii—has an “impressive research portfolio” demonstrating its digestive benefits in adults and children, with animal and in vitro studies elucidating a plausible mechanism for its action.

A recently published in vitro study2 used an ex vivo fecal fermentation model of the human gut to study the postbiotic’s effects on microbiota composition and function, with results showing an increase in the absolute abundance of Bifidobacterium species as well as smaller increases in the populations of other beneficial species.

“This influence on the composition of gut bacteria toward more favorable species such as Bifidobacteria reveals another positive attribute of postbiotics like LBiome,” Rizo notes.

Tortajada Serra cites “intriguing” preclinical research3 in suckling rats indicating that a postbiotic/prebiotic combination might offer “a potential strategy for modulating microbial and immune features in early life in this animal model,” she says. “Work like this helps expand industry understanding of postbiotics, including how they can be leveraged to further support wellness goals.”

And a recent review4 summarizing what May-Zhang calls “the state of the art of pre-, pro-, and postbiotic supplementation on immune support” concluded that microbial metabolites and soluble cell components associated with postbiotics may even extend their action into the lungs.

“Along those lines,” she continues, “a recent in vitro study5 provides evidence that the short-chain fatty acid butyrate may help combat COVID-19.” The authors found that a butyrate releaser—the same molecule as Blue California’s postbiotic BeneAll product—modulated inflammation and fought SARS-CoV-2 infection in human intestinal biopsies and enterocytes.

And while microbial byproducts like butyrate have long been the subject of study, May-Zhang notes, “Our understanding of how other metabolites like 4-ethylphenol sulfate and tryptophan-derived microbial metabolites contribute to conditions like brain function and inflammation is just beginning to be appreciated.”

Ingredients in Action

Expanding the bounds of postbiotic science is one thing; translating that science into effective wellness products, however, is another. Fortunately, it’s in just these sorts of real-world products that postbiotics show their greatest potential.

The reason lies in their stability. Whereas probiotics must remain alive to confer their benefits—from production and packaging to passage through the consumer’s digestive tract—postbiotics, by contrast, “are produced via fermentation outside the body under highly controlled conditions,” Green explains. “They’re not living organisms and are highly heat, pH, and pressure stable. These formulation advantages make it possible to deliver health benefits across a range of supplement formats—even in functional foods and beverages.”

For example, Cargill has incorporated its EpiCor postbiotic into “a new generation of gummies,” as well as other supplement formats and food and beverage prototypes, Green says.

ADM’s also been on the gummy beat, working with Remedy Health to include BPL1 HT, the heat-treated postbiotic counterpart to its BPL1 probiotic (Bifidobacterium animalis subsp. lactis CECT 8145), in Remedy’s Nourished brand of personalized, 3D-printed gummy vitamins.

While 3D printing involves temperatures too high for probiotics to withstand, Tortajada Serra explains, the highly stable BPL1 HT didn’t miss a beat in the gummies’ “unique formulation environment.” What’s more, she adds, the ingredient disperses easily in blends without detracting from the finished product’s sensory characteristics.

Leveraging Relationships

“The addition of postbiotics to the biotics toolbox now means that viability is no longer a challenge, serving as a great advantage to supplement developers and food manufacturers,” May-Zhang says. As for consumers, she continues, while they’re “open to new solutions for improving their health through the gut, the industry still has to establish clear messaging and guidance for educating the public about postbiotics and associated definitions.”

Green agrees, adding that Cargill uses this analogy in its consumer-education campaigns: “Prebiotics, like the fiber found in leafy greens, are the food for the beneficial bacteria in the gut; in essence, they fuel the factories that’re the microorganisms in our microbiome. Probiotics, such as live beneficial bacteria, add specific factories that make metabolites that may benefit health. Postbiotics contain those beneficial metabolites themselves—the goods made by the microbial factories.”

Easy-peasy, right? So easy, in fact, that the day may come when postbiotics are even better understood—to say nothing of more widely used—than pre- and probiotics. “While this is still a very new category,” Green says, “given their science-backed benefits, we’re confident that demand for products containing postbiotics will continue to grow.”

References

  1. Salminen S et al. “The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.” Nature Reviews Gastroenterology & Hepatology, vol. 18, no. 9 (September 2021): 649–667. Published online in May 2021 ahead of print.
  2. Warda AK et al. “A postbiotic consisting of heat-treated Lactobacilli has a bifidogenic effect in pure culture and in human fermented fecal communities.” Applied and Environmental Microbiology. Published online February 12, 2021.
  3. Morales-Ferré C et al. “Effects of a postbiotic and prebiotic mixture on suckling rats’ microbiota and immunity.” Nutrients, vol. 13, no. 9 (August 27, 2021): 2975
  4. Xavier-Santos D et al. “Evidences and perspectives of the use of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention and treatment of COVID-19: A bibliometric analysis and systematic review.” Trends in Food Science and Technology, vol. 120 (February 2022): 174-192
  5. Paparo L et al. “A new butyrate releaser exerts a protective action against SARS-CoV-2 infection in human intestine.” Molecules, vol. 27, no. 3 (January 27, 2022): 862