Serotonin Transporter Deficiency is Associated with Dysbiosis and Changes in Metabolic Function of the Mouse Intestinal Microbiome

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.

Case-Control Study of the Effects of Gut Microbiota Composition on Neurotransmitter Metabolic Pathways in Children With Attention Deficit Hyperactivity Disorder

“…We also found that the proportion of Enterococcus was significantly increased in the ADHD group, and Enterococcus has been reported to be closely related to neurotransmitter release. One study demonstrated that Enterococcus abundance is significantly increased in mice lacking the 5-HT transporter (Singhal et al, 2019); deficiency of this transporter can lead to decreased 5-HT levels, which is related to ADHD onset (Wang et al, 2018). Interestingly, a study showed Enterococcus could lead to excessive intestinal conversion of levodopa (the first-line treatment for Parkinson's disease) into dopamine, however, peripheral dopamine cannot penetrate the BBB to enter the CNS, thus reducing the effectiveness of levodopa (Maini Rekdal et al, 2019).…”

The gut microbiota and its interactions with cardiovascular disease

“…However, another study reported that the Coriobacteriaceae family, which is involved in urolithin B production, is positively associated with total cholesterol and LDL levels and is a potential CVD risk biomarker (Romo‐Vaquero, et al , ). Other molecules, such as indoleamine 2,3‐dioxygenase, serotonin (5‐HT) and NAPEs, are also correlated with gut microbiota changes that alter lipid absorption or lipid metabolism, consequently linking the gut microbiota to cardiometabolic phenotypes (Laurans, et al , ; May‐Zhang, et al , ; Singhal, et al , ). Melatonin improves lipid metabolism, and the potential mechanism is related to gut microbiota reprogramming, especially with respect to Bacteroides‐ and Alistipes‐ mediated acetic acid production (Yin, et al , ).…”

Seasonal Dynamics and Starvation Impact on the Gut Microbiome of Urochordate Ascidian Halocynthia roretzi

“…The arachidonic acid has an immune-enhancing effect [64]. Enteroendocrine cells within the mucosal lining of the gut synthesize and secrete a number of hormones including 5-HT, which have regulatory roles in key metabolic processes such as insulin sensitivity, glucose tolerance, fat storage, and appetite [61,65,66]. Gutderived 5-HT in shaping gut microbiota composition in relation to susceptibility to colitis, identifying 5-HT-microbiota axis as a potential new therapeutic target in intestinal inflammatory [67].…”