Serotonin Transporter (SERT) Expression Modulates the Composition of the Western-Diet-Induced Microbiota in Aged Female Mice

作者：Mirjam Bloemendaal, Ekaterina Veniaminova, Daniel C. Anthony, Anna Gorlova, Priscilla Vlaming, A. H. Khairetdinova, Raymond Cespuglio, Klaus‐Peter Lesch, Alejandro Arias Vásquez, Tatyana Strekalova · 发表于：Nutrients · 年份：2023 · DOI：10.3390/nu15133048 · 被引用次数：10 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Diet and metabolism studies

Background. The serotonin transporter (SERT), highly expressed in the gut and brain, is implicated in metabolic processes. A genetic variant of the upstream regulatory region of the SLC6A4 gene encoding SERT, the so-called short (s) allele, in comparison with the long (l) allele, results in the decreased function of this transporter, altered serotonergic regulation, an increased risk of psychiatric pathology and type-2 diabetes and obesity, especially in older women. Aged female mice with the complete (Sert−/−: KO) or partial (Sert+/−: HET) loss of SERT exhibit more pronounced negative effects following their exposure to a Western diet in comparison to wild-type (Sert+/+: WT) animals. Aims. We hypothesized that these effects might be mediated by an altered gut microbiota, which has been shown to influence serotonin metabolism. We performed V4 16S rRNA sequencing of the gut microbiota in 12-month-old WT, KO and HET female mice that were housed on a control or Western diet for three weeks. Results. The relative abundance of 11 genera was increased, and the abundance of 6 genera was decreased in the Western-diet-housed mice compared to the controls. There were correlations between the abundance of Streptococcus and Ruminococcaceae_UCG-014 and the expression of the pro-inflammatory marker Toll-like-Receptor 4 (Tlr4) in the dorsal raphe, as well as the expression of the mitochondrial activity marker perixome-proliferator-activated-receptor-cofactor-1b (Ppargc1b) in the prefrontal ...