A Gut-on-a-Chip Model to Study the Gut Microbiome-Nervous System Axis

Area of Science:

• Microbiology
• Neuroscience
• Biotechnology

Background:

• The human body hosts a vast microbial community, primarily in the gut.
• The gut microbiome's interaction with the enteric nervous system is poorly understood.
• Existing in vitro models lack the physiological relevance to study these complex interactions.

Purpose of the Study:

• To develop a physiologically representative in vitro model for studying gut microbiome-nervous system interactions.
• To investigate the communication between gut microbes and enteric neurons.
• To advance understanding of the gut microbiome-nervous system axis.

Main Methods:

• Development of the human-microbial crosstalk (HuMiX) gut-on-chip model.
• Introduction of induced pluripotent stem cell-derived enteric neurons into the HuMiX model, creating 'neuroHuMiX'.
• Co-culture of bacterial, epithelial, and neuronal cells in microfluidic channels separated by semi-permeable membranes to allow communication via soluble factors.

Main Results:

• The neuroHuMiX model successfully co-cultures diverse cell types while maintaining their separation.
• The model facilitates communication between gut microbes and enteric neurons through soluble factors.
• Initial insights into the effects of the gut microbiome on enteric neuronal cells were obtained.

Conclusions:

• The neuroHuMiX model represents a significant advancement in studying the gut microbiome-nervous system axis in vitro.
• This model provides a unique platform for dissecting the intricate crosstalk between gut microbes and the nervous system.
• Further research using this model is critical for understanding neuro-gastrointestinal health and disease.