Bacteria Engineered to Produce Serotonin Modulate Host Intestinal Physiology.

Area of Science:

• Microbiology
• Gastroenterology
• Metabolic Engineering

Background:

• Gut bacteria significantly influence host intestinal functions, including motility and homeostasis.
• The complex interplay between microbial metabolites and host physiology presents challenges in understanding gut health and disease.
• Biogenic amines produced by gut microbes are key mediators of host-microbe interactions.

Purpose of the Study:

• To engineer a gut commensal bacterium, *Escherichia coli* Nissle 1917, for the biosynthesis of the human metabolite serotonin.
• To investigate the physiological effects of microbially produced serotonin on the host gastrointestinal tract.
• To establish a novel framework for modulating luminal serotonin levels using engineered bacteria.

Main Methods:

• Genetic engineering of *Escherichia coli* Nissle 1917 to enable serotonin production.
• Oral administration of engineered bacteria to a mouse model.
• Analysis of host gut transcriptional and physiological changes post-treatment.

Main Results:

• Engineered bacteria successfully colonized the large intestine and produced serotonin in vivo.
• Mice treated with serotonin-producing bacteria showed significant biological alterations in the gut.
• Observed changes included both transcriptional and physiological modifications at the gut level.

Conclusions:

• Engineered bacteria provide a viable platform for modulating luminal serotonin levels in the gut.
• Microbially produced serotonin impacts host gut physiology, offering insights into gut homeostasis and dysfunction.
• This approach holds promise for developing novel microbial therapeutics for human gastrointestinal disorders.