Serotonin Transporter Deficiency is Associated with Dysbiosis and Changes in Metabolic Function of the Mouse Intestinal Microbiome.
Megha SinghalBenjamin A TurturiceChristopher R ManzellaRavi RanjanAhmed A MetwallyJuliana TheorellYue HuangWaddah A AlrefaiPradeep K DudejaPatricia W FinnDavid L PerkinsRavinder K GillPublished in: Scientific reports (2019)
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.
Keyphrases
- metabolic syndrome
- high fat diet induced
- gene expression
- insulin resistance
- type diabetes
- dna methylation
- cardiovascular disease
- randomized controlled trial
- white matter
- multiple sclerosis
- physical activity
- microbial community
- wild type
- uric acid
- body mass index
- replacement therapy
- escherichia coli
- clinical trial
- blood brain barrier
- functional connectivity
- resting state
- candida albicans
- fatty acid
- cell free