Abstract
Serotonin transporter (SERT) plays a critical role in regulating extracellular availability of serotonin (5-HT) in the gut and brain. Mice with deletion of SERT develop metabolic syndrome as they age. Changes in the gut microbiota are being increasingly implicated in Metabolic Syndrome and Diabetes. 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. Microbial DNA was isolated, processed for metagenomics shotgun sequencing, and taxonomic and functional profiles were assessed. 34 differentially abundant bacterial species were identified between SERT+/+ and SERT−/−. SERT−/− mice displayed higher abundances of Bacilli species including genera Lactobacillus, Streptococcus, Enterococcus, and Listeria. Furthermore, SERT−/− mice exhibited significantly lower abundances of Bifidobacterium species and Akkermansia muciniphilia. Bacterial community structure was altered in SERT−/− mice. Differential abundance of bacteria was correlated with changes in host gene expression. Bifidobacterium and Bacilli species exhibited significant associations with host genes involved in lipid metabolism pathways. Our results show that SERT deletion is associated with dysbiosis similar to that observed in obesity. This study contributes to the understanding as to how changes in gut microbiota are associated with metabolic phenotype seen in SERT deficiency.
Highlights
Serotonin (5-HT) is an important neurotransmitter in the central nervous system
While it is known that gut bacteria are able to influence host serotonergic machinery[27,28,29,30], the effect of changes in host serotonergic signaling on intestinal microbiome homeostasis has not been investigated in mice
We found that bacterial community structure is disrupted, and metabolic capabilities of the microbiome are altered in Serotonin transporter (SERT)−/− mice
Summary
The gut microbiome plays an important role in the pathogenesis of various health disorders[32,33,34,35,36]. Changes in metabolic capabilities of the gut microbiome were associated with changes in host gene expression of enzymes involved in lipid metabolism in SERT−/− mice. Our study confirms that the loss of SERT in mice is associated with gut microbial dysbiosis and this dysbiosis correlates with metabolic alterations within the host. Our data indicates that SERT plays a vital role in maintaining homeostasis of the gut microbiota, and that its deficiency leads to loss of bacterial niches and altered microbial metabolic capabilities. This is clinically relevant, as selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for treatment of depression and other psychiatric disorders. The findings of the current study establish a strong foundation for understanding the involvement of the intestinal microbiome in the pleotropic consequences of SERT deficiency
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