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Abstract Background Gut microbiota plays a key role in shaping our immune system, producing a myriad of molecules with neuro- and immunomodulatory properties. Many of these bioactive molecules are generated by bacterial metabolism of common dietary components. We have recently found that fecal samples of patients with chronic abdominal pain contain high levels of inflammatory phospholipids, lysophosphatidylcholine (LPC) and its active metabolite lysophosphatidic acid (LPA). Both phospholipids have been previously linked to genesis and maintenance of chronic neuropathic pain. In addition, they appear to have pro-inflammatory properties. Aims To investigate whether gut bacteria can produce LPC and LPA from dietary precursor phosphatidylcholine (PC), and whether these phospholipids can induce inflammatory responses in the host. Methods Fecal samples from patients with chronic abdominal pain were analyzed for microbial profiles using 16S rRNA (Illumina) analysis, and abundance of individual bacteria was correlated with fecal LPC and LPA levels as measured by ELISA. To confirm ability to produce these lipids, identified bacteria were incubated with either phosphatidylcholine (PC) or LPC (the immediate precursors of LPC and LPA, respectively) and LPC and LPA levels measured using liquid chromatography-mass spectrometry. To investigate pro-inflammatory effect of LPC and LPA, mouse splenocytes were incubated with LPC and/or LPA in vitro, and tested for cytokine production. Results Higher abundance of several bacterial species was associated with higher fecal levels of LPC and LPA. Among them, a bacterium from family Oscillospiraceae was identified as the most likely producer of both LPA and LPC; its abundance also correlated with high pain scores. Culturing and incubating this bacterium with PC and LPC resulted in a significant production of LPC and LPA. Additionally, LPA, but not LPC, resulted in increased levels of IL-6 production by splenocytes in vitro compared to the PBS only control. Interestingly, LPA induced IL-6 secretion was inhibited in the presence of LPC. Conclusions We have identified several bacterial producers of LPC and LPA, among them a bacterium from family Oscillospiraceae, which was also associated with high abdominal pain scores. LPA, but not LPC, seems to induce proinflammatory responses in the host. Further experiments are needed to identify the specific mechanisms by which these bioactive phospholipids induce abdominal pain and immune responses in the host. Funding Agencies CIHRFarncombe Family Digestive Health Research Institute
Hall-Bruce et al. (Wed,) studied this question.