The human microbiota in health and disease: the role of quorum sensing peptides

The human microbiota is known to be beneficial for health, playing a role in e.g. nutrient supply and immunomodulation. However, a changing human microbiota has been linked to several diseases as well, including cancer and psychiatric disorders. Currently, evidence indicates that these pathologies can be influenced and even initiated by i.a. the bacterial-dependent production of genotoxic agents and toxins (e.g. ROS and CagA) or the increased metabolisation of compounds (e.g. oestrogen). Our research is focused on the role of quorum sensing peptides, playing a possible role in the microbiome-host interaction. As important parallels are seen between the bacterial quorum sensing mechanisms and the biochemical and biological mechanisms that metastatic cancer cells use to function as a society of malignant cells, we investigated the effect of different quorum sensing peptides on tumor cell behavior. By the use of collagen invasion assays and Chick Chorioallantoic Membrane (CAM) assays on HCT-8 (colorectal adenocarcinoma) and MCF-7 (breast adenocarcinoma) cells, different quorum sensing peptides from Bacillus species, Streptococcus mitis, Enterococcus faecium and Escherichia coli were found to selectively promote tumour cell migration and angiogenesis in vitro. These findings were supported by microarray data and cytokine profiling after quorum sensing peptide treatment of these tumour cells. Selected quorum sensing peptides may thus potentially influence cancer metastasis, which is prognostic for the ultimate cancer outcome. As some of these quorum sensing peptides pass the intestinal epithelium, as evidenced by Caco-2 cell results, their host crosstalk effect is not limited to local effects only: once they reach the blood circulation, distant sites can be affected as well, including the brain tissue due to blood-brain barrier permeability properties of e.g. Streptococcus and Clostridium quorum sensing peptides. These results support and potentially explain the role of the microbiome in different mental disorders, thereby enlarging our knowledge about the microbiome-brain axis.The human microbiota is known to be beneficial for health, playing a role in e.g. nutrient supply and immunomodulation. However, a changing human microbiota has been linked to several diseases as well, including cancer and psychiatric disorders. Currently, evidence indicates that these pathologies can be influenced and even initiated by i.a. the bacterial-dependent production of genotoxic agents and toxins (e.g. ROS and CagA) or the increased metabolisation of compounds (e.g. oestrogen). Our research is focused on the role of quorum sensing peptides, playing a possible role in the microbiome-host interaction. As important parallels are seen between the bacterial quorum sensing mechanisms and the biochemical and biological mechanisms that metastatic cancer cells use to function as a society of malignant cells, we investigated the effect of different quorum sensing peptides on tumor cell behavior. By the use of collagen invasion assays and Chick Chorioallantoic Membrane (CAM) assays on HCT-8 (colorectal adenocarcinoma) and MCF-7 (breast adenocarcinoma) cells, different quorum sensing peptides from Bacillus species, Streptococcus mitis, Enterococcus faecium and Escherichia coli were found to selectively promote tumour cell migration and angiogenesis in vitro. These findings were supported by microarray data and cytokine profiling after quorum sensing peptide treatment of these tumour cells. Selected quorum sensing peptides may thus potentially influence cancer metastasis, which is prognostic for the ultimate cancer outcome. As some of these quorum sensing peptides pass the intestinal epithelium, as evidenced by Caco-2 cell results, their host crosstalk effect is not limited to local effects only: once they reach the blood circulation, distant sites can be affected as well, including the brain tissue due to blood-brain barrier permeability properties of e.g. Streptococcus and Clostridium quorum sensing peptides. These results support and potentially explain the role of the microbiome in different mental disorders, thereby enlarging our knowledge about the microbiome-brain axis.C