UCLA researchers in the Department of Integrative Biology and Physiology have begun to elucidate the molecular pathways for communication between the gut microbiota and the brain, serving as potential therapeutic targets for the treatment of various neurological diseases.
BACKGROUND:
The gut microbiota is recognized as an important regulator of brain function and behavior, with the capacity to affect neurogenesis, blood brain barrier integrity, immune cell activation, and symptoms of neurological disease. Despite this evidence supporting a “microbiome-gut-brain axis,” the molecular and cellular pathways underlying communication between intestinal microbes and the brain remains unclear. One hypothesis is that gut microbiota communicates with the brain directly via the vagus nerve: the major connection between the viscera and the brain that controls basic autonomic functions of the respiratory, cardiovascular, digestive, and immune systems. While this is a compelling theory, existing evidence for this hypothesis merely gives an indication of whether vagal signaling is important, but not how, precisely. Identification of the pathways responsible for modulation of vagal nerve activity by the gut microbiota has the potential to uncover novel pathways for therapeutic intervention in a variety of neurological diseases.
INNOVATION:
UCLA researchers in the Department of Integrative Biology and Physiology have begun to discover the molecular pathways of communication between the gut microbiota and the brain, serving as potential therapeutic targets in the treatment of various neurological diseases. Preliminary data by the researchers confirms that the vagus nerve is modulated by the gut microbiota. Specifically, the microbiota modulates the activity of disassociated sensory neurons, confirming the presence of molecular machinery necessary for communication between the two. Further, the ability of the gut microbiota to modulate vagal fiber activity was additionally confirmed in vivo. In particular, it was found that vagal fiber activity decreases following depletion of the microbiota with antibiotics, and can be restored with the recolonization of the small intestine with a donor microbiota. To elucidate whether the role of microbiota on vagus nerve activity was due to particular chemical species, the researchers investigated the effects of different microbial communities that operate through different metabolic pathways on vagal nerve activity. These experiments have led to a series of identified metabolites that are believed to play a direct role in the activation of the vagus nerve. This discovery of potential metabolic entities that could control vagus nerve activation could serve as novel therapeutic strategies in the treatment of neurological dieases.
POTENTIAL APPLICATIONS:
• The discovery of the molecular pathways responsible for communication between the gut and brain, could uncover new treatment targets for a series of neurological diseases.
ADVANTAGES:
• There is no current understanding of the molecular mechanisms involved in the communication between the gut and the brain by way of the vagus nerve. The research presented is therefore the only mechanism supported by preliminary research
DEVELOPMENT-TO-DATE:
The modulation of vagal nerve activity by the microbiota has been confirmed in vitro and in vivo, and metabolites responsible for this communication have been identified. Confirmation of the effects that these metabolites have on neurons is currently being conducted.
RELATED PAPERS:
Yano et al., 2015, Cell 161, 264–276.