Limosilactobacillus reuteri ATCC 6475 metabolites upregulate the serotonin transporter in the intestinal epithelium
Open Access
- 16 November 2021
- journal article
- research article
- Published by Brill in Beneficial Microbes
- Vol. 12 (6), 583-600
- https://doi.org/10.3920/bm2020.0216
Abstract
The serotonin transporter (SERT) readily takes up serotonin (5-HT), thereby regulating the availability of 5-HT within the intestine. In the absence of SERT, 5-HT remains in the interstitial space and has the potential to aberrantly activate the many 5-HT receptors distributed on the epithelium, immune cells and enteric neurons. Perturbation of SERT is common in many gastrointestinal disorders as well as mouse models of colitis. Select commensal microbes regulate intestinal SERT levels, but the mechanism of this regulation is poorly understood. Additionally, ethanol upregulates SERT in the brain and dendritic cells, but its effects in the intestine have never been examined. We report that the intestinal commensal microbe Limosilactobacillus (previously classified as Lactobacillus) reuteri ATCC PTA 6475 secretes 83.4 mM ethanol. Consistent with the activity of L. reuteri alcohol dehydrogenases, we found that L. reuteri tolerated various levels of ethanol. Application of L. reuteri conditioned media or exogenous ethanol to human colonic T84 cells was found to upregulate SERT at the level of mRNA. A 4-(4-(dimethylamino) phenyl)-1-methylpyridinium (APP+) uptake assay confirmed the functional activity of SERT. These findings were mirrored in mouse colonic organoids, where L. reuteri metabolites and ethanol were found to upregulate SERT at the apical membrane. Finally, in a trinitrobenzene sulphonic acid model of acute colitis, we observed that mice treated with L. reuteri maintained SERT at the colon membrane compared with mice receiving phosphate buffered saline vehicle control. These data suggest that L. reuteri metabolites, including ethanol, can upregulate SERT and may be beneficial for maintaining intestinal homeostasis with respect to serotonin signalling. Download Figure Download figure as PowerPoint slideKeywords
This publication has 142 references indexed in Scilit:
- Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel diseaseMicrobial Cell Factories, 2013
- Activation of Colonic Mucosal 5-HT4 Receptors Accelerates Propulsive Motility and Inhibits Visceral HypersensitivityGastroenterology, 2012
- 4-(4-(Dimethylamino)phenyl)-1-methylpyridinium (APP+) Is a Fluorescent Substrate for the Human Serotonin TransporterOnline Journal of Public Health Informatics, 2012
- Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life -- a double-blind, placebo-controlled studyAlimentary Pharmacology & Therapeutics, 2011
- Serotonin Activates Dendritic Cell Function in the Context of Gut InflammationThe American Journal of Pathology, 2011
- Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporterNeurogastroenterology & Motility, 2010
- Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosisNature Medicine, 2010
- Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in ratsJournal of Hepatology, 2009
- Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitisAlcohol, 2009
- Serotonin Signaling in Diverticular DiseaseJournal of Gastrointestinal Surgery, 2008