Melanie Bush, chief science officer of Artemis International, a supplier of dark berry ingredients branded as Berryceuticals, spoke with NutraIngredients-USA about this developing line of research.

She said this growing body of evidence is providing new avenues of approach to consumers and potential customers about her company’s elderberry ingredient, long touted for its immune system support potential.

Evidence for activity of polyphenols in gut​

The evidence connecting polyphenolic ingredients to improved measures of gut health has been piling up in recent years.

For example, a 2015 study done with 244 subjects showed how a blend of polyphenols improved various measures of intestinal comfort ​​associated with gastroenteritis including gas, bloating and frequency of diarrhea.

Another more recent review study showed that while polyphenols as a class have generally low bioavailability, with at best 10% of the amount of the ingested molecule making it across the gut barrier into the bloodstream, the compounds do have a striking positive effect on the composition of the gut microbiota​​.

Bush said the most recent study of the bunch, performed at the Washington University School of Medicine in St. Louis, provides a strong case for the relationship between flavonoid-rich foods, gut microbes, and immune efficacy​​.

The presence of DAT (desaminotyrosine), a compound identified as being a metabolite in the gut after the consumption of key flavonoids present in elderberry, actually helps protect against damage from influenza (Steed et al. 2017​​). Therefore, a healthy balance of gut microbiota as well as flavonoid-rich foods/supplements like elderberry appear to be the magic cocktail for positively impacting immune health.

“Every other year there is a gathering, the Berry Symposium, a forum where recent research is shared. Over the years the message has gone from ‘Berries are good for you,’ to more of a question of how are they good for you. One of the more recent takeaways is that it is all connected by the gut,”​ Bush said.

Is bioavailability the wrong thing to stress about?​

The bioavailability question is one that has plagued research in the field for years, Bush said. Study after study showed positive benefits, but if so little of the purported active ingredients were crossing into the blood and interacting with tissues beyond the endothelium, what exactly was going on?

Without a focused method of action, it became difficult to construct a complete narrative, and to figure out the best ways to possibly improve an ingredient’s function. A lot of effort has been devoted in recent years toward improving the bioavailability of hard-to-absorb polyphenolic ingredients, for example. But if a lot of really important reactions connected to these ingredients and their health effects are happening in the gut mucosal layer, might this ultimately prove to be a case of inadvertently putting the cart before the horse?

“Flavonoids, and anthocyanins in particular, have been perplexing because they have always exhibited very low bioavailability. Now we are starting to understand that they and the other flavonoids are behaving more like prebiotics and are modulating the composition of the microbiota. They are creating a more favorable environment,”​ Bush said.

In the question of immune support, Bush said a more complete mechanism of action is starting to come into view for elderberry.

Other immune support ingredients, such as Kerry’s Wellmune, have had this kind of information for years. In the case of Wellmune, a beta glucan ingredient that was isolated from the cell walls of fungi, the ingredient binds to certain receptors on immune system cells, priming them for more immediate response in the case of infection without overheating the immune system as a whole.

Elderberry isn’t at that stage yet, but with the research detailing the role of DAT, it has taken a step closer, Bush said. And part of that process is understanding more fully how the gut is a key player in these effects, and not just a transport system from ingestion point A (the mouth) to activity point B (the immune cells in the blood.)

“We are now starting to understand more specifically how they are affecting the immune response. We are understanding how the microbiome and these anthocyanins are intimately connected to each other,”​ Bush said.

Spreading the research across many species​

The Steed study done in St. Louis is connected to the metabolic activity of a single organism: Clostridium orbiscindens​. But with hundreds of species making up a healthy microbiome, the story won’t stop there, Bush said.

“This is definitely an area that is going to require more research before we can identify specific species and what they are doing when they metabolize anthocyanins. This particular Clostridium species has shown anti influenza effects by producing this very helpful metabolite from flavonoids,”​ she said.

That research could also point the way toward future product development, by showing from a microbiome perspective products that might have synergistic effects at the level of the gut mucosal layer. And Bush said it might also help shed light on why some people benefit from a natural dietary ingredient while others show little or no response. Could it have to do with the makeup of their microbiome, which arises from a combination of genetic and lifestyle factors?

“I do believe that what we are seeing from the science so far is pointing in the direction of blends and products that work together and support a health benefit from various angles. And that research could help answer the question of why for so many botanical products there is a big range of responders and non-responders,”​ Bush said.