Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut

Nat Microbiol. 2019 Dec;4(12):2064-2073. doi: 10.1038/s41564-019-0540-4. Epub 2019 Sep 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Bacteria / drug effects
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Firmicutes / drug effects
  • Fluoxetine / administration & dosage*
  • Gastrointestinal Microbiome / drug effects*
  • Genetic Variation
  • Host Microbial Interactions / drug effects
  • Intestines / microbiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Selective Serotonin Reuptake Inhibitors / administration & dosage*
  • Serotonin / administration & dosage*
  • Serotonin Receptor Agonists / administration & dosage*
  • Specific Pathogen-Free Organisms

Substances

  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin

Supplementary concepts

  • Turicibacter sanguinis