June/July 2020 Issue

Discover the World of Postbiotics
By Mindy Hermann, MBA, RDN
Today’s Dietitian
Vol. 22, No. 6, P. 20

Research shows these bioactive compounds derived from fermented foods may provide unique benefits to gut health.

First came probiotics, then prebiotics, and now there’s postbiotics, the newest member of this family of “-biotics” substances—microbes, food components, nutrients, and metabolites—that may affect gut health.

Probiotics, for example, are beneficial microorganisms in the gut, while prebiotics are substrates, often fibers selectively utilized by host microorganisms, that offer health benefits. Put simply, prebiotics are food for probiotics.

Given that people still confuse probiotics with prebiotics, growing use of the term postbiotics is bound to generate even more questions. So what are postbiotics? How are they related to prebiotics and probiotics? And how are postbiotics connected to the burgeoning trend of fermented foods?

Introducing Postbiotics
Scientists and gut experts have known about postbiotics and their benefits for years, but the term doesn’t yet have an official definition. Language has been proposed to define postbiotics as bioactive compounds produced by food-grade microorganisms during the fermentation process of a food or beverage, which are ingested in the fermented product, resulting in various benefits in the gut of the host.1 Fermented foods and beverages contain bioactive peptides and living microorganisms that could modulate immune responses and impact the composition of the intestinal microbiota.2

Microorganisms produce waste products as part of their metabolic process. The bacteria and yeast strains used in fermentation generate a combination of metabolites, such as short-chain fatty acids (SCFAs), functional proteins, and peptides, along with discarded matter from the microorganisms themselves, which include cell wall components and extracellular polysaccharides.1

What makes these substances stand out is their beneficial effects on the gut of the host, that is, humans. The broad definition of postbiotics also incorporates inactivated microbial strains. (The terms paraprobiotics and ghost probiotics are used by some research groups to define nonviable probiotic strains that, when administered in sufficient amounts, confer benefits to the host. This language mirrors that of probiotics, prebiotics, and postbiotics—conferring benefits when taken in adequate amounts.)

Postbiotics are being examined more closely for their potential health benefits, including anti-inflammatory, immunomodulatory, antiobesogenic, antihypertensive, hypocholesterolemic, antiproliferative, and antioxidant activities.3 They also may boost the immune system and improve gut barrier function.

And they may offer key advantages compared with probiotics; because postbiotics aren’t live, they’re more stable and have a longer shelf life than live, active probiotics.

Postbiotics don’t require strict production or storage conditions to keep them alive, making them suitable for developing countries that have inconsistent access to refrigeration and processing.

Postbiotics also may present an alternative for boosting gut health in critically ill patients, young children, and premature neonates who are immunocompromised and shouldn’t consume live, active cultures.

Relationship Between Fermentation and Postbiotics
To understand the relationship between postbiotics and fermentation, it’s important to know about the fermentation process. Fermented foods have been defined as “foods or beverages made via controlled microbial growth and enzymatic conversions of major and minor food components.”4 In fermentation, different microbes act on key ingredients to generate compounds specific to the microbe and the end product. For example, yeasts produce the alcohol and carbon dioxide found in beers and breads; acetobacteria produce acetic acid, the acid in vinegar; lactic acid bacteria produce lactic acid in dairy products, sauerkraut, and pickles; and the lesser-known Propionibacterium freudenreichii bacteria generate the classic taste and texture of Swiss-type cheeses. (It’s important to note that the bacteria cultures in fermented foods usually aren’t considered probiotics, even though they may come from the same “family”—for example, lactic acid bacteria.)

These classic fermentation byproducts, including acetic and lactic acids, aren’t the bioactive postbiotics; other compounds generated during fermentation are responsible for the fermentation health halo.

The live microbes involved in fermentation enhance nutritional value of the fermented food by converting unsaturated fatty acids to conjugated linoleic acids; increasing bioavailability of B vitamins, vitamin K, magnesium, and zinc; reducing antinutrients such as phytates; and enhancing content of polyphenols. The biologically active compounds that fermentation microorganisms produce are considered postbiotics: Conjugated linoleic acids have blood pressure–lowering and anti-inflammatory properties; sphingolipids have anticarcinogenic and antimicrobial properties; functional peptides have been associated with antioxidant, antimicrobial, opioid antagonist, antiallergenic, and blood pressure benefits; and extracellular polysaccharides can function as prebiotics.1

For example, sourdough bread appears to deliver health benefits, in part, from the impact of its fermentation process on the carbohydrate content of bread. Fermentation lowers the content of FODMAPs because the sourdough yeasts Saccharomyces cerevisiae and Kluyveromyces marxianus degrade oligosaccharides during the sourdough process.5 This results in a sourdough bread that people with irritable bowel syndrome (IBS) and sensitivities to FODMAPs can more easily tolerate.

The high temperature for baking sourdough bread typically kills the live microorganisms, but metabolites and cell fractions remain intact. In comparison, fermented foods that aren’t processed after fermentation deliver both postbiotics and the live microorganisms that produce the postbiotics.

Activities in the Gut
The current working definition of postbiotics refers specifically to compounds and fermentation waste products generated outside of the body. A similar process, however, occurs in the gut. Like fermentation bacteria, bacteria in the gut of healthy adults, known as commensal or native bacteria, generate fermentation metabolites with physiological benefits. Commensal bacteria, which typically are a combination of anaerobic Firmicutes (Clostridium, Enterococcus, Lactobacillus, Faecalibacterium) and Bacteroidetes (Bacteroides, Prevotella), include strains similar to some types of fermentation bacteria in fermented foods. Likewise, their byproducts and benefits are similar to those of fermented foods and beverages. In the future, it’s possible that fermentation byproducts in the gut also will be referred to as postbiotics.

This is where prebiotics come in, playing a similar role to fermentable compounds outside of the body. Prebiotics have been defined as “food for the beneficial microbes that live in our gut. They provide health benefits for humans by selectively promoting the growth of beneficial bacteria. Prebiotics are found naturally in some fruits and vegetables, are enriched in a variety of food products, including infant formula, and are available as dietary supplements. Most prebiotics are dietary fibers, but not all dietary fibers have a prebiotic effect.”6

“Fermentable fibers are prebiotics that help support the metabolism of commensal microbes in the gut,” says Hannah Holscher, PhD, RD, an assistant professor of nutrition in the Nutrition and Human Microbiome Laboratory in the department of food science and human nutrition at the University of Illinois at Urbana-Champaign. “These microbes generate metabolic products such as the short-chain fatty acids acetate, proprionate, and butyrate that have been shown to confer a range of potential health benefits, including reducing systemic inflammation, aiding in glycemic control, supporting weight loss, and increasing calcium absorption.”

The gut microbiome also produces the neurotransmitters dopamine, serotonin, and norepinephrine that impact mental health.

Commensal gut bacteria often are confused with probiotics. The key difference is that commensal gut bacteria live in the body full time while probiotics are just passing through. Think of the gut as a town, with commensal gut microbes as the homeowners and probiotics as guests in the local hotel. Some probiotics guests may stay longer than others, but none are permanent residents in town.

Probiotics often differ from the bacteria used in fermentation. “The main difference between any bacteria that is used to make a fermented food and probiotics lies in the definition of a probiotic,” says Maria Marco, PhD, a professor in the department of food science and technology at the University of California, Davis. “Microbes must have three characteristics to fit the definition of a probiotic: One, they must be living; two, they must confer a scientifically substantiated health benefit; and three, they must be consumed in adequate amounts to confer that health benefit.

“Because fermented foods typically contain undefined microbial strains that haven’t been shown to benefit health as strains themselves, those foods shouldn’t be considered probiotic. ‘Live and active cultures’ is a good term to apply to fermented foods, rather than probiotic,” she continues.

Some dairy products and nondairy alternatives, however, are fermented with both fermentation and probiotic strains.

Both prebiotics and postbiotics mainly support commensal bacteria. Postbiotics created during the fermentation process can impact the composition and functioning of the commensal human gut microbiome. They provide the native microbe population with substrates for generating SCFAs and also help inhibit potential pathogens.1

Fermented foods and beverages offer individual sets of potential benefits: Kefir provides antimicrobial activity from its organic acids, bacteriocins, carbon dioxide, hydrogen peroxide, ethanol, and diacetyl; kombucha retards pathogen growth from its low pH and high concentration of acetic acid; and sauerkraut confers potential health benefits from conjugated linoleic acid.7 Fermented milk delivers antioxidant, antihypertensive, antidiabetic, and antiallergic potential via its phenolic compounds, conjugated linoleic acid, GABA (gamma-aminobutyric acid), and the peptides lactalbumin, lactoglobulin, and casein.2,5 Grain fermentation generates similar types of compounds, along with proteolytic activity by lactic acid bacteria that convert cereal proteins into bioactive peptides (postbiotics).2 Soybean fermentation produces vitamin B12. Lactobacillus plantarum in fruit fermentation creates phenolic compounds and several organic acids.

“We’re beginning to learn more and more about how microbes interact with their environment within the intestine,” Marco says. “Fermented foods can confer health benefits by increasing the number of living microbes we’re consuming, transforming food components such as lactose, and synthesizing new compounds.”

Postbiotics and the Sensitive Gut
While postbiotics in fermented foods have the ability to improve the health of the microbiome, the sensitive gut presents numerous challenges to dietitians working toward an optimal approach that maximizes both nutrition and comfort for clients. It’s thought that an imbalance in gut microbes may contribute to the development and exacerbation of inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.

Recent studies suggest postbiotics may help restore immune response by improving the health of the gut microbiome; supporting messaging between gut microbes and the immune system; influencing cell proliferation, differentiation, migration, and death; and boosting function of mucosal and systemic immunity.8

A growing body of studies suggests that postbiotics, including fermentation products and inactivated lactobacilli, are safe to use, have positive effects on gastrointestinal functioning, and can be part of treatment for diarrhea related to IBS. Postbiotics are thought to work both directly and indirectly, externally through fermentation that generates antipathogenic organic compounds, and internally by providing substrates that nourish the gut microbes producing beneficial SCFAs.

Production of SCFAs may help lower inflammatory bowel disease risk and improve the activity of the mucosal barrier in the intestine. Postbiotics hold promise as products generated by microbes that could serve as new and safer therapies for inflammatory diseases.8 In addition, postbiotics may play a role in the health of the developing infant.

Postbiotics and Infants
Among the unique features of human breastmilk are nondigestible prebiotic human milk oligosaccharides (HMOs) that play a crucial role in shaping the infant gut microbiome. HMOs pass through the digestive tract undigested, reaching the intestinal tract intact for fermentation by beneficial bacteria such as bifidobacteria. This supports the growth and health of the bacterial colonies and helps regulate gut activity.

One type of infant formula, “fermented infant formula without live bacteria,” mimics the prebiotic features of human breastmilk and delivers potential benefits of postbiotics created during fermentation. The company Nutricia created a mixture, scGOS:lcFOS (9:1), with more than 100 short-chain galactooligosaccharides, or scGOS, and long-chain fructooligosaccharides, or lcFOS, in a 9:1 ratio designed to mimic the HMO diversity and concentration in human breastmilk. Added to a fermented infant formula, this combination of HMOs and postbiotics has been shown to be safe and well tolerated in healthy term newborns.

In four combined randomized clinical trials, supplementation with heat-killed Lactobacillus acidophilus LB similar to the strains used in fermented infant formula reduced the duration of diarrhea. The results of two polled randomized clinical trials show heat-inactivated Lactobacillus paracasei CBA L74 vs placebo reduced the risk of diarrhea.9 However, studies on postbiotics for diarrhea in young children have shown mixed results overall, so caution is recommended pending additional studies.

Advice to Dietitians
Kate Scarlata, MPH, RDN, LDN, a FODMAP and IBS expert and owner of her private practice, For a Digestive Peace of Mind, LLC, in Medway, Massachusetts, through which she counsels clients with complicated gastrointestinal issues, has found that response to postbiotics and prebiotics varies from client to client.

“In contrast to postbiotics with beneficial effects, histamine, a postbiotic product of fermentation, may exacerbate IBS symptoms in some people. In addition, a prebiotic such as resistant starch can increase the SCFA butyrate, but only if the individual has gut microbes that can both break down resistant starch and create butyrate as a result. It’s not an automatic process that occurs in everyone—it’s based on what microbes inhabit the gut and what they’re capable of doing. The same holds true for response to postbiotics,” Scarlata says, adding that gas production via fermentation can contribute to luminal distention, leading to bloating, cramping, and pain in people with a sensitive gut.

It’s possible the definition of postbiotics will be expanded to include the similar compounds produced by commensal gut bacteria. “While the term ‘postbiotics’ may be new to dietitians, decades of research into the compounds produced by the bacteria in the lower digestive tract has revealed an abundance of health benefits,” says David Feder, RDN, author of The Skinny Carbs Diet. “A healthy gut requires a combination of approaches—prebiotic fiber to feed commensal bacteria, probiotics to confer specific benefits, and postbiotics.”

However, Holscher acknowledges the danger of overpromising benefits from postbiotics. “Fermented foods are associated with a range of health benefits, but it can be hard to tease apart the effects of microbes from nutrients and other compounds in the foods,” she says.

— Mindy Hermann, MBA, RDN, is a food and nutrition communications consultant in metro New York.


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