The Microbiota-Derived Metabolite Deoxycholic Acid Regulates Enteric Neuron Activity and Connectivity

Area of Science:

• Neuroscience
• Microbiology
• Gastroenterology

Background:

• Secondary bile acids (BAs) are gut microbiota metabolites influencing digestive functions via the enteric nervous system (ENS).
• Enteric neurons express the BA receptor Takeda G protein-coupled receptor 5 (TGR5), but their direct response to BAs is unclear.
• The impact of microbial metabolites on ENS connectivity and synaptic activity is largely unexplored.

Purpose of the Study:

• To investigate the effects of secondary BAs on enteric neuronal connectivity and function.
• To elucidate the role of deoxycholic acid (DCA) in modulating ENS synaptic activity and neurotransmission.

Main Methods:

• Primary rat enteric neuron cultures were exposed to deoxycholic acid (DCA).
• Changes in presynaptic protein expression (synapsin-1, synaptophysin) and synaptic density were assessed.
• Synaptic activity, vesicle exocytosis, intracellular calcium responses, and TGR5 receptor involvement were analyzed.

Main Results:

• DCA exposure increased synapsin-1 and synaptophysin expression and enhanced synaptic density in enteric neurons.
• DCA augmented synaptic activity by increasing synaptic vesicle exocytosis, potentially via synapsin-1 phosphorylation.
• DCA modulated acetylcholine-induced calcium responses through a TGR5-mediated mechanism.

Conclusions:

• Deoxycholic acid (DCA) reshapes the enteric neuronal functional network by enhancing connectivity and synaptic activity.
• Bacterial metabolites like DCA act as a link between the microbiome and ENS function.
• Secondary BAs play a significant role in digestive physiology and may be implicated in gastrointestinal disorders.