The history and promising future of synbiotics

The following excerpt is from a longer article in the Probiotics digital magazine. Click the link to access it in full and learn more about published synbiotic research, including which strains play nicely together.

In 1995, professors Glenn Gibson and Marcel Roberfroid introduced the world to the word “prebiotics.”

But the corresponding Journal of Nutrition article, aptly titled, “Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics,” didn’t stop at dropping one pivotal term into the world’s nutritional lexicon.¹ “We thought that mixing pro and pre together made sense,” Gibson explained via email, “so we decided to include synbiotics in the review, too.”

So, make that two pivotal terms—and while synbiotics aren’t as ubiquitous in the supplement world as prebiotics, if current scientific research is any indication, they soon will be.

The paper defined synbiotics as, “A mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal [GI] tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria, and thus improving host welfare.”

In other words, synbiotics are a mix of probiotics and prebiotics that work together in a targeted way to benefit the “good” bacteria in a person’s gut.

Synbiotics played a blink-and-you’ll-miss-it role in the research article. Still, over a quarter-century later, the idea is catching on. Grand View Research predicted in its “Synbiotic Product Market Size, Industry Growth Report, 2027” that the global synbiotic market will be worth $1.3 billion by 2027.

However, a lot has changed since 1995. “One thing is that there is a lot more information—tens of thousands of research papers,” Gibson said. “I think the concepts are quite well accepted but not too well understood by consumers, mainly because health claims based on the science need more clarity.”

“As far as consumers understand it, when they do understand it, it’s a combination of prebiotics and probiotics,” affirmed Len Monheit, executive director of the Global Prebiotic Association (GPA), a trade group focused on increasing public awareness of prebiotics (and synbiotics, by association). “Synbiotics need to be, in my opinion, a targeted combination that operates synergistically and additively, so that one plus one equals three.”

This lack of understanding may not be limited to consumers. “There is currently some debate in the industry around the definition of synbiotics,” Kristin Wilhoyte, global director of product marketing at ingredient supplier Deerland Probiotics and Enzymes, explained. “While synbiotics may generally refer to the combination of probiotics and prebiotics, the International Scientific Association for Probiotics and Prebiotics’ (ISAPP) definition shows that this doesn’t necessarily have to be the case.”

ISAPP is an industry-backed association of academic and industrial scientists focusing on probiotics, prebiotics and related substances. Given the evolution of the science since Gibson and Roberfroid coined the term synbiotic, the organization has worked to create a new definition that will, hopefully, make both regulation and innovation easier.

To best understand this definition, it’s important first to understand the definitions of its components, probiotics and prebiotics.

Step one: Probiotics

Scientists have known for decades that humans are covered with bugs, inside and out. The microscopic critters are on the skin and teeth and all up and down the gut. By one estimate, people have 10 trillion human cells in their body, but 100 trillion bacteria.²

These bacteria form colonies that impact the body in good and bad ways. An example of a “bad” bacterium is H. pylori, which can infect the stomach, causing inflammation and ulcers, per a reference book on the medical database StatPearls. “Good” bacteria include Lactobaccilus acidophilus, often found in yogurt. It colonizes in the digestive and urinary tracts, mitigating an assortment of gut issues.³

Probiotics are live bacteria that one ingests that may help support good bacteria colonies. Various fermented foods typically offer some degree of probiotic activity, such as yogurt, kimchi and kombucha. But if a product has been pasteurized without live beneficial bacteria being reintroduced, it’s likely no longer probiotic.

Typically, probiotic supplements contain billions of bacterial cells, quantified in a measurement of colony-forming units (CFUs). Formulators often include higher-than-labeled amounts of them in products to account for decreases in viability throughout shelf life.

Then there are prebiotics

Prebiotics are substances that promote the growth of good bacteria. When Gibson and Roberfroid were writing their 1995 article, Gibson wanted to call them “parabiotics” in honor of the paramedics on the television show “M*A*S*H.” “A parabiotic would help biotics, right?” Gibson opined. “I still think I was right, but in the end, we went with prebiotics.”

Beloved '70s sitcoms aside, different prebiotics can benefit different probiotics—and there are a lot of them. Many prebiotics are various types of carbohydrates known as oligosaccharides.⁴ Some phytonutrient polyphenols also function as prebiotics.⁵ The list goes on from there, including “so many other discrete compounds, different mechanisms, different functions—all with different health benefits,” Monheit said.

Prebiotics naturally occur in many foods, including chicory root, garlic, onion, leeks and green bananas.

The interaction between prebiotics and bacteria creates short-chain fatty acids (SCFAs), including butyrate, which may play a role in gut and immune system health.⁶ These byproducts of “biotic” activity are sometimes referred to as “postbiotics.”⁷

Better together, synbiotics

While Gibson and Roberfroid came up with the term synbiotics, they didn’t invent the interaction between pre- and probiotics. Technically, fermented foods like sauerkraut and kimchi contain both the beneficial bacteria and the oligosaccharides that feed them.⁸ However, according to ISAPP Executive Science Officer Mary Ellen Sanders, Ph.D., they haven’t been thoroughly researched from a synbiotic perspective.

“Fermented foods might have a microbe that reaches a certain level, plus you might have certain fiber. You could imagine that they could work together,” she said, “but we don't know of any science that I’m aware of that really shows that these things are true synbiotics.”

As the understanding of synbiotics progressed over the decades, in May of 2019, ISAPP assembled a group of nutritionists, physiologists and microbiologists—including Gibson—to update the definition of synbiotics, as well as recommend guidelines for associating the term synbiotic with a product. This resulted in “The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics.”⁹

The statement splits the definition into two types—complementary synbiotics and synergistic synbiotics.

Complementary synbiotics are defined as a “mixture of probiotic(s) and prebiotics(s). Each works independently to achieve one or more health benefits.” Synergistic synbiotics are defined as a “mixture of a selectively utilized substrate and a live microbe chosen for its ability to deliver a health effect. Components comprising synergistic synbiotics work together to bring about resulting health benefit(s).”

While complementary synbiotics need to contain clinical levels of both pre- and probiotics, synergistic synbiotics do not. Instead, they just need to have a proven mechanism—meaning they need to be clinically shown to work together. Also, synergistic synbiotics don’t need to contain a prebiotic per se. They just need to contain a substrate that works synergistically with the accompanying probiotic.

ISAPP created this second definition to foster innovation. “In our conception, you really shouldn't have to jump through all those hoops in place to make sure that probiotics and prebiotics are appropriately designed,” explained Sanders, who also served on the panel. “What you should have to do is jump through those hoops to make sure that the combination meets the appropriate requirement for a health benefit.”

The conclusion of this article—including a slew more of scientific studies using specific strains of synbiotic combinations—is available here: Probiotics digital magazine.

Denis Faye, MS, is a nutrition communications consultant, journalist and athlete committed to changing people's lives for the better. He has written for dozens of publications including The New York Times, The Los Angeles Times, Outside, Men’s Health, and Men's Journal. You can read his sports nutrition ramblings at denisfaye.substack.com.

References

1 Gibson GR et al. “Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics.” J Nutr. 1995;125(6):1401-1412.

2 Linares DM et al. “Beneficial Microbes: The pharmacy in the gut.” Bioengineered. 2016;7(1):11-20.

3 Remes-Troche JM et al. “Lactobacillus acidophilus LB: a useful pharmabiotic for the treatment of digestive disorders.” Therap Adv Gastroenterol. 2020;13.

4 Davani-Davari D et al. “Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications.” Foods. 2019;8(3):92.

5 Alves-Santos AM et al. “Prebiotic effect of dietary polyphenols: A systematic review.” J Funct Foods. 2020;74:104169.

6 Tan J et al. “The role of short-chain fatty acids in health and disease.” Adv Immunol. 2014;121:91-119.

7 Wegh CAM et al. “Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond.” Int J Mol Sci. 2019;20(19):4673.

8 Jovanovic-Malinovska R et al. “Oligosaccharide Profile in Fruits and Vegetables as Sources of Prebiotics and Functional Foods.” Int J Food Prop. 2014;17(5):949-965.

9 Swanson KS 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;17:687-701.