How Your Gut Tells Your Brain That You’re Hydrated

The Context: It might only take a couple seconds after a gulp of water to no longer feel thirsty, but for your brain to know you’re rehydrated, it needs to consult your gut. How this line of communication works, however, is not well understood.

The Study: New research in Nature from NYSCF – Robertson Neuroscience Investigator Yuki Oka, PhD, identifies the major sensory pathway that mediates how the gut communicates about hydration with the brain.

The Importance: This study paves the way for better understanding of how the brain processes sensory information.

While drinking water might satiate us right away, the entire process of rehydration takes longer: roughly half an hour. The brain needs to know quicker than that if we have enough water, so it relies on the gut rather than the bloodstream to tell it that it’s satiated. 

Sensory neurons in the gut detect and measure osmolality levels (the concentration of dissolved materials including sodium and glucose) to tell the brain whether thirst is quenched, but scientists hadn’t known much about the pathway that mediates this connection.

The Two Paths of the Gut

Dr. Oka’s team at CalTech used genetically engineered mice to examine two pathways known to connect the gut and the brain: the spinal (dorsal root ganglia, or DRG) and vagal pathways. The team administered water, salt, or sugar into the mouse’s gut and monitored these pathways.

The scientists saw that it was the vagal neurons that responded to osmolality changes in the gut, with different groups of neurons activating in response to different liquids.

From Bowel to Brain

The team next investigated which part of the gut was sending these signals. They turned to the hepatic portal area (HPA), a major blood vessel running through the gut that absorbs nutrients from the intestine and carries them to the liver. 

The vagal nerves present in the HPA were, in fact, sending osmolality signals to the brain, it seemed. The scientists next turned their attention to how the vagal nerves were sensing osmolality – whether directly or indirectly.

They found that a certain peptide called the vasoactive intestinal peptide, or VIP, is secreted in the gut when thirst is satiated, in turn activating vagus nerves in the HPA to tell the brain ‘we’re good on water.’

“We have discovered the beginning of a pathway, the HPA-to-brain axis,” noted Dr. Oka in an article from CalTech. “The details of all of the connections and molecular mechanisms are still to be determined.”

Future research will further explore the connection between the gut and the brain to regulate thirst. Dr. Oka’s lab previously identified ‘thirst neurons’ in the brain that are highly active when animals are thirsty, but that rapidly calm down after drinking water. These thirst neurons aren’t connected to the gut, so the researchers will examine how these neurons know when the body is rehydrated.

Journal Article:

Sensory representation and detection mechanisms of gut osmolality change
Takako Ichiki, Tongtong Wang, Ann Kennedy, Allan-Hermann Pool, Haruka Ebisu, David J. Anderson & Yuki Oka. 2022. Nature. DOI: https://doi.org/10.1038/s41586-021-04359-5

Image credit: Yuki Oka, Michelle Williamson and Charles Zuker