Polyphenols: The next generation of prebiotics is ready for liftoff

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Nutritional OutlookNutritional Outlook Vol. 28, No. 4
Volume 28
Issue 4

Explore the prebiotic health benefits of polyphenols and the positive impact they may have on digestive and immune health. Polyphenols, such as those found in European black elderberry, may be an ideal solution for manufacturers trying to break into the digestive health space.

Image | adobe.stock/VIS Fine Arts

Image | adobe.stock/VIS Fine Arts

Mysterious gases, dark corners teeming with strange lifeforms and tantalizing secrets that scientists spend their entire careers working to decode; are we talking about a distant alien planet, or the human digestive system? Though they represent opposite ends of the micro- to macroscopic scale, the fields of gastroenterology and astronomy have a surprising amount in common, not least their tendency to cause confusion. Just as questions persist surrounding the inner workings of outer space, many consumers remain unclear on the topic of their gut health, and how best to support it. One clear fact is that ‘good’ bacteria, or probiotics, are key to strengthening and diversifying the gut microbiome, which in turn can support our well-being.1 Holding with the comparisons to space travel, probiotics are the rocket that transports us to reduced gastric discomfort,2 improved immunity3 and even better mood management,4 but whether literal or figurative, they need the right fuel: prebiotics. These less well-known, yet equally essential cousins, act as catalysts for the beneficial bacterial strains on which our guts depend. Prebiotics officially recognized by the Scientific Association for Probiotics and Prebiotics (ISAPP) and the Global Prebiotic Association (GPA) include chicory fiber and other dietary fibers like inulin, resistant starches, certain oligosaccharides and polyphenols.5 Polyphenols, a category of plant-based molecules, may be the next big thing in the nutraceutical industry, thanks to their capacity to support gut health and potential to meet evolving consumer preferences.

Read on as we embark on a journey into the vast potential of polyphenols as prebiotic rocket fuel, and the latest scientific research set to blast the topic into a whole new frontier of opportunity.

Prepping the launch pad

Before anything else, let’s go over some essential definitions. For 30 years, scientists, nutritionists and governing bodies have tried to establish a single description of the features that constitute a prebiotic, with little success. Until late 2024, the closest to a unified definition was “a substrate that is selectively utilized by host microorganisms conferring a health benefit.”6 As our understanding of prebiotics and their effects on the body has developed however, so too has the official definition. In recognition of locations of action outside the intestine, the GPA recently recommended that the previous standard of selectivity should be removed, and put forward a new definition for prebiotics: “a compound or ingredient that is utilized by the microbiota producing a health or performance benefit.”6 Happily, the definition of polyphenols – “a diverse class of secondary plant metabolites possessing unique chemical structures and varying functions”7 – has been less controversial, but even more obscure to the general public.

Straightforward explanations like this provide essential context, but in isolation they’re not the most effective route to consumer engagement. Interest in both prebiotics and polyphenols has expanded over the last decade, but according to data from the International Food Information Council (IFIC) only a quarter of survey respondents actively try to consume prebiotics, compared with the almost 40% who state they are increasing their consumption of probiotics.8 It’s clear further work is needed to wake consumers up to the benefits of focusing as much on the ‘fuel’ as the rocket itself.

With this in mind, what are the advantages functional food and supplements brands could highlight to raise awareness and demonstrate the value of prebiotics? The most obvious answer is digestive health support, specifically stimulating the growth of beneficial bacterial strains,9 the production of gut-barrier enhancing short-chain fatty acids (SCFAs)9 and the reduction of complaints such as gas, bloating and abdominal pain.10 But in today’s disease-conscious climate however, it’s prebiotics’ impact on immune responses that offers particular promise – and it’s here that polyphenols truly step into the spotlight.

Raising the shields

We tend to think of immunity primarily in the context of white blood cells, but with its highly sensitive “pathogen recognition patterns,” the colonic epithelium (the lining of the large intestine) arguably plays an even greater role in rallying the body’s defense system. However, disease, stress and the effects of a poor diet can all impact the integrity and thickness of its mucosal lining, leading to the overgrowth of “bad” bacteria (dysbiosis) and “leaky gut” syndrome.3 An unbalanced gut microbiome and compromised epithelial layer can lead to increased inflammation, metabolic disturbances and—most pertinently—a weakened or overactive immune response.3

As non-digestible substances, prebiotics pass from the stomach to the large intestine, where they help re-establish the immune-supporting function of the gut’s mucosal barrier, guard against the production of damaging free radicals by reducing oxidative stress, and create optimal conditions for the growth of ‘good’ bacteria at the expense of less beneficial strains.3

While several categories of prebiotics have been shown to impart such effects, emerging research points to polyphenols—such as those derived from European black elderberry (Sambucus nigra) fruit—as particularly effective in promoting the growth of the essential strains Akkermansia, Bifidobacteria and Lactobacilli.11 In addition to the beneficial effects of its anthocyanin content on microbial diversity,12 the flavonoids present in black elderberry can bind directly to the virus particles, preventing them from attaching to red blood cells to replicate.13

Though elderberries have been a feature in traditional cold and flu remedies for hundreds of years, their status as a prebiotic ingredient with legitimate immunostimulant properties14 is a relatively recent development. Now however, with a growing body of scientific evidence behind them, anthocyanin-standardized black elderberry extracts offer nutraceutical brands a unique opportunity to address some of the modern world’s most fundamental health concerns, just as consumers are truly starting to take notice.

Twenty-first century food woes

In theory, a balanced diet, rich in high-fiber foods, such as lentils, bananas and oats, is enough to keep prebiotic levels stable. But the realities of everyday life often leave even otherwise healthy digestive systems hungry for support.

Much of the issue comes down to a serious diversity problem. As much as three quarters of the world’s food is derived from only 12 plants and five animal species15 and this homogenous dietary palate is generating generally weaker gut microbiomes that are more susceptible to dysbiosis and diseases.6 Consumers are of course seeking answers to this bad gut feeling, even if many aren’t fully aware of the science underlying prebiotics’ effects on digestive health, immunity and metabolism.16 Given this lack of knowledge, secondary factors such as convenience, naturalness and environmental credentials become equally powerful purchase drivers.

Indeed, in a survey of major supplement producers, 88% stated customer expectations were ‘very’ or ‘fairly’ important in motivating companies to adopt more sustainable production practices.17 The expectation that supplements be naturally effective is another key factor, with the pervasive attitude being that such products are healthier, safer and better for the environment—but also potentially less powerful than synthetic alternatives.18 Trend data like this paints a clear picture; shoppers feel that something crucial is missing from their diets, and want to turn to natural solutions to fill the gap but are skeptical regarding their effectiveness. With their fruit origins and built-in consumer trust, polyphenols were already set to address conscious consumer preferences, and now exciting clinical data is also emerging to bolster their status as natural powerhouses. 

Science spotlight: Black elderberry extract, good bacteria and a better gut feeling

Until relatively recently, the microbiota-directed effects of European black elderberry extract have remained somewhat of a mystery —one that researchers at Johannes Kepler University, Austria were determined to bring into the light through an investigation into the effects of a three-week supplementation with black elderberry extract on a group of healthy adults.11

Participants were asked to keep a diary of digestive symptoms, beginning three weeks prior to supplementation and extending three weeks after, data from which was compared to weekly biospecimen testing and three evenly-spaced blood tests. From weeks four to seven, the participants ingested a daily dose of 600 mg of a standardized black elderberry extract (ElderCraft; manufactured by Iprona and distributed in the U.S. by Artemis International) which was assessed to contain 18% polyphenol content per dose, equivalent to that of 30 g of raw fruit.

The introduction and withdrawal of the intervention at weeks four and seven of the trial produced significant changes in the measures of microbial α- and β-diversity found within participants’ biospecimen samples. Overall, 92 bacterial taxa (identified at the species level) were assessed to be differentially abundant in samples pre-, during- and post-intervention weeks compared with the participants’ median microbial abundance at baseline.11 Since these sudden changes in diversity closely aligned with the ingestion of black elderberry extract, researchers surmised that supplementation with this polyphenol-rich ingredient produced a relevant microbiome-shaping capacity—in short, demonstrating its value as a prebiotic ingredient.11

The fuse is lit

Like the countdown to ignition at a rocket launch, there’s a point in time just before an ingredient catapults into the mainstream that’s especially valuable to nutraceutical producers. Polyphenols like European black elderberry extract are the latest solution to enter in this dynamic phase in market relevance—offering the exciting potential to nourish the gut, naturally. This intersection between powerful yet lesser-known, novel yet unintimidating, is rich in possibilities for supplement producers and health-conscious consumers alike, and one worth seizing before the fuse runs down and this prebiotic rocket fuel truly ignites the sector.

  1. Patel R.M.; Denning PW. Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: what is the current evidence? Clin Perinatol. 2013, 40(1),11-25. DOI: 10.1016/j.clp.2012.12.002. PMID: 23415261; PMCID: PMC3575601.
  2. Selvaganapathi G.; Jinat Ahmed J.A.; Mathialagen, A.G.; Dinesh, M.; Azra, N.; Harikrishnan, T.; Kohila, J.R.; Fathy, L.; et al. Meta-Analysis Study the Role of Probiotics Treatment in Irritable Bowel Syndrome (1990-2017). Journal of Food and Nutrition Research. 2018, 6 (11):710-718. DOI: 10.12691/jfnr-6-11-6
  3. Lefevre M.; Racedo, S.M.; Ripert, G.; Housez, B.; Cazaubiel, M.; Maudet, C.; Justen, P.; Marteau, P.; Urdaci, M.C. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immune Ageing. 2015, 12, 24. DOI: 10.1186/s12979-015-0051-y
  4. Baião, R.; Capitão, L.P.; Higgins, C.; Browning, M.; Harmer, C.J.; Burnet, P.W.J. Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study. Psychological Medicine. 2023, 53 (8), 3437-3447. DOI: 10.1017/S003329172100550X
  5. Global Prebiotic Association. Prebiotic Resources. https://prebioticassociation.org/prebiotic-resources/
  6. Deehan, E.C.; Antwan, S.A.; Witwer, R.S.; Guerra, P.; John,, T.; Monheit, L. Revisiting the Concepts of Prebiotic and Prebiotic Effect in Light of Scientific and Regulatory Progress—A Consensus Paper From the Global Prebiotic Association. Advances in Nutrition. 2024, 15 (12), 100329. DOI: 10.1016/j.advnut.2024.100329.
  7. Rodríguez-Daza, M.C.; Pulido-Mateos, E.C.; Lupien-Mielleur, J.; Guyonnet, D.; Desjarddins, Y.; Roy, D. Polyphenol-Mediated Gut Microbiota Modulation: Toward Prebiotics and Further. Front. Nutr. 2021, 8, 689456. DOI: 10.3389/fnut.2021.689456
  8. International Food Information Council. 2021 Food & Health Survey. May 19, 2021. https://foodinsight.org/2021-food-health-survey/
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  11. Reider, S.; Watschinger, C.; Längle, J.; Pachmann, U.; Przysiecki, N.; Pfister, A.; Zollner, A.; Tilg, H.; Plattner, S.; Moschen, A.R. Short- and Long-Term Effects of a Prebiotic Intervention with Polyphenols Extracted from European Black Elderberry—Sustained Expansion of Akkermansia spp. J. Pers. Med. 2022, 12, 1479. DOI: 10.3390/jpm12091479
  12. Swaminathan, K; Dyason, J.C.; Maggioni, A.; Von Itzstein, M.; Downard, K.M. Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry. Anal Bioanal Chem. 2013, 405 (20), 6563-6572. DOI: 10.1007/s00216-013-7068-x
  13. Roschek, B.; Fink, R.C.; McMichael, M.D.; Li, D.; Alberte, R.S. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009, 70 (10), 1255-61. DOI: 10.1016/j.phytochem.2009.06.003.
  14. Kinoshita, E.; Hayashi, K.; Katayama, H.; Hayashi, T.; Obata, A. Anti-influenza virus effects of elderberry juice and its fractions beyond. Biosci Biotechnol Biochem. 2012. 76(9), 1633-1638. DOI:10.1271/bbb.120112
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