AUTOINDUCER-2 SIGNALLING IN PROBIOTICS: A MECHANISM OF GUT MICROBIOTA MODULATION

Park H., Lee K., Yeo S., Shin H., Holzapfel W.
Handong Global University, South Korea

Introduction:
Bacterial symbioses are vital in the human host. Gut microbiota, in particular, are closely associated with physiological traits and several diseases. Therefore, a major focus has shifted to the potential of probiotics as bacterial therapeutics for modulating the gut microbiota. Several recent studies on the impact of microbiota modulation by selected functional strains in specific disease models are supporting this concept. However, mechanisms of the modulation by probiotics administration have not been fully elucidated, thus severely limiting prediction and control of modulatory effects on the bacterial community.

Bacteria-bacteria interactions are primary events in any bacterial community. Among these, bacterial quorum sensing, cell-density dependent and secretory signalling systems provide valuable opportunities for unveiling mechanisms of the bacterial community construction. In particular, the LuxS-mediated autoinducer-2 (AI-2) signalling system is found in a wide variety of Gram-positive and Gram-negative bacteria, including Lactobacillus spp. It has been reported to regulate the expression of genes associated with specific adaptation and resistance to the environment. The signalling system also correlates with bacterial colonisation and adhesion to the host epithelial cell. Furthermore, recent studies suggest that AI-2 activity can support restoration of the balance between the phyla Firmicutes and Bacteroidetes in antibiotic-induced dysbiosis.
It is therefore expected that the AI-2 signalling status may influence a change in bacterial survival and even modulation of the gut microbial composition.

Methods:
AI-2 signalling properties of 104 probiotic lactobacilli were analysed using a modified AI-2 bioluminescence assay for lactic acid bacteria. In order to evaluate the influence of AI-2 signal status on bacterial community changes, a synthesized AI-2 molecule and non-specific quorum signalling inhibitor were applied the human stool and C57BL/6J mouse experimental models. The bacterial community of each sample was analysed using qRT-PCR and 454 GS-FLX platinum pyro-sequencing based on the 16S rRNA gene.

Results:
Treatment of the human stool with AI-2 molecules resulted in a dose dependent change in composition ratio of Firmicutes/Bacteroidetes compared to the control. The tendency was also shown in shifts at the level of families and genera. Also the bacterial community distance matrix showed diverting changes in microbiota following AI-2 addition and inhibition. In the in vivo mouse model, modulatory effects differed significantly from the human stool model.
Our investigations showed Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus brevis, and Lactobacillus lactis to be AI-2 producing species, while Lactobacillus johnsonii and Lactobacillus sakei showed AI-2 inhibition features. In the case of Lactobacillus acidophilus, AI-2 production and inhibition were strain-specific. The differences in AI-2 signalling properties of probiotic Lactobacillus species or strains infer widely different bacterial interactions in the human gastrointestinal tract.

Discussion:
Although the AI-2 signalling in gut bacteria is still insufficiently understood, our results suggest the AI-2 signalling property of probiotics to be a key mechanism by which gut microbiota are modulated.

Keywords: Gut microbiota modulation, Probiotics, Quorum sensing, Autoinducer-2, Bacterial interaction

Citation:
Park H., et al. (2016). Autoinducer-2 signalling in probiotics: A mechanism of gut microbiota modulation. Conference Proceedings of IPC2016. Paper presented at the International Scientific Conference on Probiotics and Prebiotics, Budapest (p. 56.). IPC2016

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