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Serotonin transporter4/6/2023 ![]() Optimal levels of 5-HT are maintained via the serotonin transporter (SLC6A4, SERT) which actively imports 5-HT, allowing for its degradation by intracellular monoamine oxidases 8, 9. 5-HT has diverse roles in the GI tract which include regulating mucosal homeostasis, increasing motility, and modulating electrolyte transport 1, 2, 3, 4, 5, 6, 7. However, approximately 95% of total body 5-HT is present in the gastrointestinal (GI) tract. Serotonin (5-HT) is an important neurotransmitter in the central nervous system. This study contributes to the understanding as to how changes in gut microbiota are associated with metabolic phenotype seen in SERT deficiency. Our results show that SERT deletion is associated with dysbiosis similar to that observed in obesity. Bifidobacterium and Bacilli species exhibited significant associations with host genes involved in lipid metabolism pathways. Differential abundance of bacteria was correlated with changes in host gene expression. Bacterial community structure was altered in SERT −/− mice. Furthermore, SERT −/− mice exhibited significantly lower abundances of Bifidobacterium species and Akkermansia muciniphilia. SERT −/− mice displayed higher abundances of Bacilli species including genera Lactobacillus, Streptococcus, Enterococcus, and Listeria. 34 differentially abundant bacterial species were identified between SERT +/+ and SERT −/−. ![]() Microbial DNA was isolated, processed for metagenomics shotgun sequencing, and taxonomic and functional profiles were assessed. To investigate the relationship between the gut microbiome and SERT, this study assessed the fecal and cecal microbiome profile of 11 to 12 week-old SERT +/+ and SERT −/− mice. Changes in the gut microbiota are being increasingly implicated in Metabolic Syndrome and Diabetes. Mice with deletion of SERT develop metabolic syndrome as they age. Serotonin transporter (SERT) plays a critical role in regulating extracellular availability of serotonin (5-HT) in the gut and brain.
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