Bacteria induce the release of proalgesic lipids by epithelial cells
(2019) United European Gastroenterology Week — Location: Barcelona, Spain
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- Abstract
- Irritable bowel syndrome is the most common functional intestinal disorder. It is characterized by visceral hypersensitivity and an altered gut transit that are associated with a gut microbiota dysbiosis. Among the studied pronociceptive mediators, host and bacterial lipid compounds have been described as major regulators of visceral hypersensitivity. The aim of our study was to identify the role of the host and bacterial lipids interplay on visceral hypersensitivity. Methods: To differentiate bacterial and host lipids, Escherichia coli were cultivated in a minimal medium with 13C- glucose as unique source of carbon, leading to the production of 13C-labelled bacterial lipids. Bacterial lipid extracts were added at the apical side of polarized intestinal epithelial cells (caco2) cultured in transwell. Twenty four hours after treatment, quantification by high-resolution mass spectrometry of the 13C-labelled lipids from the bacteria and the unlabeled lipids from the epithelial cells in the basolateral compartment allowed us to determine epithelial and bacterial lipids that could potentially be in contact with nerve endings. Lipid quantification by liquid chromatography coupled to tandem mass spectrometry was performed in the colon of germ free and conventional mice. We then assessed the ability of the epithelial and bacterial lipids found in the basolateral compartment to increase intracellular calcium concentration in primary culture of mouse sensory neurons. Results: Amongst the uniformly 13C-labelled bacterial lipids, we identified long chain fatty acids, from 10 to 18 carbons, hydroxylated on the 3rd carbon with or without a double bound, and aminolipids in the bacterial culture. Twenty four hours after treatment by bacterial lipids at the apical side of the transwells, we quantified an increase of the concentration of bacterial C10-3OH, C12AsnOH and C14AsnOH as well as epithelial 9,10-DiHOME and 12,13-DiHOME in the basolateral compartment. Similar results were obtained when the bacterial lipids were unlabeled, meaning that these results were not due to the labelling. We found a significantly lower concentration of 9,10- and 12,13-DiHOME in the colon of germ-free mice, strengthening the link between the microbiota and the host production of those lipids. Bacterial lipids and 12,13-DiHOME did not activate sensory neurons. In contrast, the 9,10-DiHOME induced calcium flux in sensory neurons. This effect was inhibited by a pretreatment of the neurons with a TRPV1 antagonist (AMG9810). Conclusion: Our study show that bacterial lipids induce the release of potentially proalgesic lipids by epithelial cells. Lipid metabolism could be the link between dysbiosis and visceral pain in IBS.
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Petitfils, C., & et al. (2019). Bacteria induce the release of proalgesic lipids by epithelial cells. United European Gastroenterology Week, Barcelona, Spain.