The benefits and challenges of synbiotic dietary supplements

November 8th, 2022

In the last years, synbiotic supplements have emerged as an interesting approach to improve gut health. Instead of using only pre- or probiotics, synbiotic products combine both. There are two types of synbiotics, namely complementary and synergistic synbiotics. Currently, most of the synbiotics on the market are complementary products since the formulation and research of synbiotics are quite challenging. In this article, we will explain synbiotic supplements in more detail, including the benefits and formulation challenges.


What are synbiotic dietary supplements?

The international scientific association for Probiotics and Prebiotics (ISAPP), defines synbiotics as: “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host” (1).

There are two types of synbiotic products: complementary and synergistic synbiotics. Complementary synbiotics are the most found on the market. This type should contain pre- and probiotic compounds that clinically show a health benefit together, but also when used independently from each other. Hence, they do not have to interact with each other.

On the other hand, synergistic synbiotics do not necessarily contain pro- or prebiotic compounds. Instead, they should contain microorganisms and substrates that are selectively utilized by the provided bacteria in the product. In this case, the combination should have a greater beneficial effect than the microorganisms or substrates independently (2).

Curious to know about prebiotics? Find out more!

What are the benefits of synbiotic dietary supplements?

Pre- and probiotic products can have beneficial effects on gut health, immune function and the production of beneficial metabolites such as short-chain fatty acids. Synbiotic products could have the same health effects, and they potentially decrease cardiovascular risk factors, markers of insulin resistance and prevalence of metabolic syndrome as well (3).

Furthermore, synbiotic formulations must contain living bacterial strains and the substrates that can be used by these bacterial species specifically. In this way, the species have the chance to feed themselves, proliferate, and adhere to the intestinal wall of the host.

Another advantage of such synergistic dietary supplement formulations, is that they could address the “responder/non-responder” phenomenon (2).

The “responder/non-responder” phenomenon means that some subjects respond to a pre- or probiotic product, whereas others do not experience any beneficial effect. The difference could be caused by the fact that everyone has a unique microbial composition in the gut and therefore reacts differently to the treatments.

By providing the bacterial strains and their substrates simultaneously, the supplied bacteria will have an advantage compared to other bacterial strains that were already present in the gut, since they already have their selectively fermentable substrate to grow on. They could subsequently outcompete some resident microbial strains and establish a niche in the gut.

In other words, the substrate serves as a sort of fertilizer for the supplied bacterial strains and increases the chance that the bacterial strain will colonize and establish in the gut. In this way, it may be more likely that a subject will respond to the supplement or product and experience a beneficial effect!

The main challenges in formulating synbiotic dietary supplements

Although synergistic synbiotics have a lot of potential, formulating them comes with some challenges:

  • Prebiotics or substrates often need to be consumed in larger amounts to have a beneficial effect, which may go along with gastro-intestinal complaints such as feeling bloated or flatulence. To limit these complaints, prebiotics may be added in lower doses, risking the loss of their beneficial health effects.
  • Microorganisms are highly sensitive to the environment, which makes it difficult to store the synbiotic products under many circumstances.
  • The water activity of the substrate: Water activity is a measure of water in a product that is available to react with or attach itself to other material, also known as ‘free’ water. Products with a higher water activity are more likely to be affected by bacteria and fungi. Therefore a substrate with a low water activity should be chosen (4).

Besides formulation challenges, researching the synergistic synbiotic effects comes with some difficulties.

The synbiotics that are now often used in studies have been formulated based on criteria such as shelf life, cost, and availability, rather than on metabolic, functional or other characteristics of the microorganisms or substrates.

In most studies, Lactobacilli and Bifidobacteria are included as the probiotic component and inulin, various oligosaccharides, or dietary fibres are chosen as prebiotic ingredient, yet only one human trial showed beneficial effects (5, 6).

To screen for new promising synbiotics, in vitro studies will first be performed because clinical trials are very expensive and time-consuming. In vitro models simulating the lower and upper gastrointestinal can be helpful, such as the TIM1 and TIM2 model. The TIM-2 model is a dynamic gastrointestinal model, which is used for in-vitro research.

These models can be used to assess the survival of a probiotic through the gastrointestinal tract and the effect of synbiotics on gut microbiota.

MicrobiomeX®: the ingredient of choice for your synbiotic formula

To limit the gastro-intestinal complaints caused by high dosages of substrates, other substrates that have beneficial effects in lower dosages, such as polyphenols, could be used. The polyphenols can be transformed into bioactive molecules or into metabolites that can be used by other microorganisms, eventually resulting in a health benefit for the host.

MicrobiomeX® is a first-in-class Flavobiotic® researched and developed by BioActor. It is a natural ingredient from citrus, consisting of two active flavanones: hesperidin and naringin. BioActor combined these two powerful phenolic compounds in a unique complex ideal for the formulation of synbiotic dietary supplements in doses ranging from 250 to 500 mg.

Thanks to its proven high stability in combination with probiotics and its low water activity, MicrobiomeX® is an ideal ingredient to formulate synbiotic dietary supplements. Specifically, MicrobiomeX® can be used as a substrate, and can be metabolized in the gut by bacteria possessing the ramnosidase enzymes such as Lactobacillus acidophilus LA-5, Lactobacillus Brevis and B. animalis ssp. Lactis (7).

After being metabolized, not only does MicrobiomeX® promote the growth of beneficial bacteria in the gut, but the active metabolites that are released in the gut exert a direct antioxidant and anti-inflammatory effect resulting in improved overall gut health.