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Nat Microbiol. 2019 Sep 2. doi: 10.1038/s41564-019-0540-4. [Epub ahead of print]

Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut.

Author information

1
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA. tcfung@g.ucla.edu.
2
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
3
Computational Structural Biology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
4
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA. ehsiao@g.ucla.edu.

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.

PMID:
31477894
DOI:
10.1038/s41564-019-0540-4

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