Quorum Sensing - a new tool for selecting feed additive ingredients

Nutriad has demonstrated the use of Quorum Sensing (QS) as a tool in the development of two new feed additives: one for broiler production and one for aquaculture. QS Is a form of bacterial communication that is critical to bacterial virulence. By investigating the ability of several highly bioactive compounds to inhibit QS, Nutriad was able to select a combination of components that, in in vivo models, had a positive effect on the viability of microbially-challenged simple model organisms at sub-MIC concentrations. Furthermore, these prototype additives were shown to be efficacious in improving zootechnical performance of production animals under field conditions. 

Gut health is one of several factors important to obtaining optimum efficiency and profitability in livestock production and there is increasing evidence of the central role played by gut microbiota in animal health and disease. Many feed additives are therefore designed to specifically support gut health. 

When selecting ingredients that affect gut bacteria, such as botanical components, many feed additive producers often rely on in vitro experiments that demonstrate their bacteriostatic effect. However, the active ingredients of these botanicals will end up in the digestive tract of production animals at concentrations far below the minimal concentration needed to inhibit growth of (pathogenic) bacteria. 

A more reliable approach might be to select feed additive ingredients based on the effects botanical (and other) components can have at much lower concentrations that are more likely to be relevant to gut health improvement. An example of a test with which sub-MIC effects of bioactive components can be explored is QS. 

QS Is a bacterial signaling process that is critical for several biochemical responses, including the production of several virulence factors. Molecules that inhibit QS have the potential, therefore, to be used to fight pathogens by decreasing their virulence rather than killing them directly. QS As a potential tool to combat humans diseases is being investigated currently while research on pathogens relevant to animal production is also expanding. 

Reducing QS in the gastro-intestinal tract is an interesting approach to control gut microbial activity and composition, and the potential for QS-inhibition as a means of improving animal health has been reported in several research papers. Furthermore, the probability that bacteria will build up resistance against these products is low due to the fact that 1) phytochemicals can disrupt distinct QS signal transduction steps (e.g. production, secretion and uptake of signaling molecules, binding to the specific receptors, modification of signal transducing proteins and activation of DNA by transcription factors) thereby reducing the chance of a single mutation rendering the bacteria resistant and 2) the selective pressure for molecules that only suppress bacterial functions (rather than kill the organism) is much lower as it does not affect bacterial growth and viability. 

Using Quorum Sensing, Nutriad has been able to select (from a list of botanicals with known beneficial effects on animal performance) a combination of components that almost completely abolished QS signaling in vitro at very low concentrations. These mixtures also had a positive effect at sub- MIC concentrations on the viability of microbially challenged organisms in two in vivo models, Vibrio and  C. elegans. In subsequent field trials, these botanical mixtures improved health and performance in poultry and aquaculture species, arguing for the potential of QS to be used as a tool to select for botanical ingredients. 

The importance of QS in production animals is currently not fully clear and many pitfalls and possible (dis)advantages of inhibiting QS remain to be investigated However, Nutriad believes that, in order to increase the chance of selecting the highest performing bioactive components in vivo, it is vitally important that the effect that these substances can exert at low concentrations are explored and QS is a potential promising tool to be considered for such investigations.