학술논문
Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut
Document Type
Original Paper
Author
Source
Nature Microbiology. 4(12):2064-2073
Subject
Language
English
ISSN
2058-5276
Abstract
The gut microbiota regulates levels of serotonin (5-hydroxytryptamine (5-HT)) in the intestinal epithelium and lumen1–5 . However, whether 5-HT plays a functional role in bacteria from the gut microbiota remains unknown. We demonstrate that elevating levels of intestinal lumenal 5-HT by oral supplementation or genetic deficiency in the host 5-HT transporter (SERT) increases the relative abundance of spore-forming members of the gut microbiota, which were previously reported to promote host 5-HT biosynthesis. Within this microbial community, we identify Turicibacter sanguinis as a gut bacterium that expresses a neurotransmitter sodium symporter-related protein with sequence and structural homology to mammalian SERT. T. sanguinis imports 5-HT through a mechanism that is inhibited by the selective 5-HT reuptake inhibitor fluoxetine. 5-HT reduces the expression of sporulation factors and membrane transporters in T. sanguinis, which is reversed by fluoxetine exposure. Treating T. sanguinis with 5-HT or fluoxetine modulates its competitive colonization in the gastrointestinal tract of antibiotic-treated mice. In addition, fluoxetine reduces the membership of T. sanguinis in the gut microbiota of conventionally colonized mice. Host association with T. sanguinis alters intestinal expression of multiple gene pathways, including those important for lipid and steroid metabolism, with corresponding reductions in host systemic triglyceride levels and inguinal adipocyte size. Together, these findings support the notion that select bacteria indigenous to the gut microbiota signal bidirectionally with the host serotonergic system to promote their fitness in the intestine.
The gut microbiota regulates levels of serotonin (5-HT) in the gut, affecting the mammalian nervous system. But does 5-HT affect the microbiota? Here, it is shown to increase the relative abundance of spore-forming members of the gut microbiota and enhance mouse colonization by Turicibacter sanguinis, a gut bacterium that can take up 5-HT and modulate systemic lipid homeostasis.
The gut microbiota regulates levels of serotonin (5-HT) in the gut, affecting the mammalian nervous system. But does 5-HT affect the microbiota? Here, it is shown to increase the relative abundance of spore-forming members of the gut microbiota and enhance mouse colonization by Turicibacter sanguinis, a gut bacterium that can take up 5-HT and modulate systemic lipid homeostasis.