The gut microbiome is the collection of microorganisms that inhabit the gastrointestinal tract1. A favourable composition of the gut microbiome is beneficial for health and can be supported with nutrition1.

In terms of supplements that can be used to augment a diet and support a more beneficial balance of bacteria in the gut microbiome, prebiotics and probiotics are terms that everyone is more familiar with. However, as a newer addition to the health and wellbeing lexicon, the category of synbiotics is less widely known. The concept of synbiotics was introduced in 1995, originally loosely defined as a mixture of probiotics and prebiotics that beneficially affects the host, selectively stimulating the growth and/or activating the metabolism of one or a limited number of health-promoting bacteria, and thus improving host welfare2. For an example of a potential synbiotic, a combination of oligosaccharides that belong to the class of prebiotics, because of their strong bifidogenic activity, could be combined with bifidobacteria to produce a synbiotic. To remove any uncertainty with the synbiotic definition, a consensus statement has recently been made by the International Scientific Association for Probiotics and Prebiotics (ISAPP) on synbiotics, providing an updated definition3.

Why was the consensus statement made by ISAPP?

The consensus statement for synbiotics was necessary because the original definition lacked precision. Additionally, the consensus statement for synbiotics and the definition is the first step for future research on synbiotics3. There are human health benefits from synbiotic ingredients and research in the years to come could find novel uses and applications. To continue the work on synbiotics, it will be important to determine causality and the mechanisms of action for prebiotics and probiotics3. To create a foundation for this potential avenue of discovery, it was important that synbiotics could be accurately defined without room for individual interpretation.

The ISAPP panel decided on a testable definition that could be utilised by researchers, industry, public health professionals and regulatory agencies updating it to:

A mixture, comprising live microorganisms and substrate(s) selectively utilized by host microorganisms, that confers a health benefit on the host4.

The definition looks to provide two distinct types of synbiotic action – complementary and synergistic. It was recognised that the non-digestible substrate used in a synbiotic may not be a prebiotic by definition on its own, or the microorganism may not be a standalone probiotic, but together could confer a health benefit. This is how the definition for a synergistic synbiotic came about and is defined with the addition of: “the substrate is designed to be selectively utilised by the co-administered microorganism(s)—and do not necessarily have to be individual probiotics or prebiotics, as long as the synbiotic itself is health promoting”4. In contrast, a complementary synbiotic is when an established probiotic is combined with an established prebiotic designed to target indigenous microorganisms— therefore each component of a complementary synbiotic must meet the minimum criteria for a probiotic or a prebiotic3.

The definition is purposefully inclusive, so a synbiotic could be established for different hosts, for example, a synbiotic could be designed more specifically for humans, animal companions or agricultural animals. Additionally, they can be designed for specific demographic subsets of hosts e.g., specific age or living situation or to target areas of the host’s body, such as skin4. The consensus statement confirms that where a health benefit is seen in the study of synbiotics, this needs to be measured using validated methods for biomarkers or symptoms of the health benefit4. There are study design recommendations set out in the consensus statement for research in the area of synbiotics. The different types of synbiotics have different recommendations in line with their definitions. A single study must demonstrate both selective utilisation of the substrate and a health benefit conferred by the synergistic synbiotic. It is only necessary to show a health benefit of the combined ingredients; it is not necessary to show selective utilisation of the prebiotic substrate, since selective utilisation should have already been established for complementary synbiotics4.

The application of synbiotics

Synbiotics have shown successful modulation of the gut microbiome, although the health benefits need to be studied further5. The new definitions will provide more clarity and uniformity for future research, and by doing so, help to create a more robust platform for future synbiotic developments.

A placebo-controlled clinical trial demonstrated the effects of a synbiotic including a combination of probiotic bacteria L. acidophilus, B. lactis, B. longum, B. bifidum and a prebiotic mixture of galactooligosaccharides (GOS) on the gut microbiome, alongside changes to body composition and metabolic markers. A group of 20 initially obese (mean BMI of 33.5 kg/m2) weight-loss participants were randomised into a placebo or synbiotic intervention group. Both groups were on the same dietary plan (a low-carbohydrate, high-protein dietary pattern with reduced energy intake), with either placebo or synbiotic supplement6. There was a significant increase in the probiotic genera in the gut of the group using the synbiotic supplement after the 3-month intervention in comparison to the control group. Glycated haemoglobin (HbA1c) levels, a glycaemic marker, decreased over time in correlation with the rise in lactobacillus with the synbiotic intervention, demonstrating a potential beneficial effect where increasing lactobacillus levels can reduce blood glucose levels6.

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Butyrate producing bacteria increased with the synbiotic intervention. Butyrate, a short chain fatty acid (SCFA) that provides an energy source for the colonocytes and a histone deacetylase inhibitor, was linked to anti-cancer effects, thus providing protection against toxic metabolites that are produced on a high protein diet. Introducing the synbiotic altered the gut microbiome to one that was less proteolytic, which could be beneficial to the host6. The application of synbiotics in the above study was to correct an aberrant gut microbiome in obesity or following an imbalanced diet. The placebo group saw an increased genotoxicity associated with the high protein, low carbohydrate and energy restricted diet. The intervention demonstrated that a synbiotic can counteract the microbial fermentation associated with a high protein diet and increased the abundance of microbial species to be of benefit to the host. Including a prebiotic provides substrate for the probiotic bacteria that may otherwise not receive the prebiotics required when consuming a low carbohydrate and energy restricted diet6.

In conclusion

The introduction of the ISAPP consensus statement provides a basis for future research using synbiotics. The use of synbiotics in specific populations, or in circumstances such as a weight loss intervention, provides rationale for the use of synbiotics for health applications, where they may be more beneficial than prebiotics or probiotics on their own. More research is required on synbiotics, using the new guidance for research from the ISAPP consensus statement.


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