title: Escherichia coli Nissle 1917 enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance.
abstract: Accumulating evidence shows indigenous gut microbes can interact with the human host through modulation of serotonin (5-HT) signaling. Here we investigate the impact of the probiotic Escherichia coli Nissle 1917 (EcN) on 5-HT signalling in gut tissues. Ex-vivo mouse ileal tissue sections were treated with either EcN or the human gut commensal MG1655, and effects on levels of 5-HT, precursors, and metabolites, were evaluated using amperometry and high performance liquid chromatography with electrochemical detection (HPLC-EC). Exposure of tissue to EcN cells, but not MG1655 cells, was found to increase levels of extra-cellular 5-HT. These effects were not observed when tissues were treated with cell-free supernatant from bacterial cultures. In contrast, when supernatant recovered from untreated ileal tissue was pre-incubated with EcN, the derivative cell-free supernatant was able to elevate 5-HT overflow when used to treat fresh ileal tissue. Measurement of 5-HT precursors and metabolites indicated EcN also increases intracellular 5-HTP and reduces 5-HIAA. The former pointed to modulation of tryptophan hydroxylase-1 to enhance 5-HT synthesis, while the latter indicates an impact on clearance into enterocytes through SERT. Taken together, these findings show EcN is able to enhance 5-HT bioavailability in ileal tissues through interaction with compounds secreted from host tissues.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nzakizwanayo
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dedi
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: Guy
authors.initials: G
authors.lastname: Standen
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Macfarlane
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: Bhavik A
authors.initials: BA
authors.lastname: Patel
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, United Kingdom.|Queen Victoria Hospital NHS Foundation Trust, East Grinstead, RH19 3DZ, United Kingdom.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Jones
mesh_terms: D000818:Animals; D001682:Biological Availability; D004926:Escherichia coli / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D012701:Serotonin / Q000378:metabolism* / Q000493:pharmacokinetics; D009435:Synaptic Transmission
chemical_list: D005227:Fatty Acids; D012701:Serotonin