Limosilactobacillus reuteri ATCC 6475 metabolites upregulate the serotonin transporter in the intestinal epithelium.

Autor:	Engevik M; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Department of Regenerative Medicine & Cell Biology, Medical University of South Carolina, 173 Ashely Ave, BSB 626, Charleston, SC 29425, USA., Ruan W; Department of Pediatrics, Baylor College of Medicine, 6701 Fannin Street, Houston, TX 77030, USA.; Section of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, 6701 Fannin St, Houston, TX 77030, USA., Visuthranukul C; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Pediatric Nutrition Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Shi Z; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Department of Pathology, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030, USA., Engevik KA; Department of Molecular Virology & Microbiology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 7703, USA., Engevik AC; Departments of Surgery, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN 37232, USA., Fultz R; Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0625, USA., Schady DA; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Department of Pathology, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030, USA., Spinler JK; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Department of Pathology, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030, USA., Versalovic J; Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.; Department of Pathology, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	Beneficial microbes [Benef Microbes] 2021 Nov 16; Vol. 12 (6), pp. 583-599. Date of Electronic Publication: 2021 Sep 22.
DOI:	10.3920/BM2020.0216
Abstrakt:	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.
Databáze:	MEDLINE
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