Is There a Second Brain in the Human Gut?

Scientists have known for years that humans have a “second brain” of autonomous neurons in their long, winding digestive tract. But now, research shows that scientists have categorized 12 different kinds of neurons in the enteric nervous system (ENS) of mice, which is similar to that of humans. This “fundamental knowledge” unlocks a huge number of paths to new experiments and discoveries.

This “gut brain” has a huge effect on how your body works. Your digestive system has an important daily job to do as part of your metabolism. However, it is also subject to fluctuations in how it functions, which is related to your emotions.

Digestive symptoms and anxiety can be related. Also, your gut is heavily affected by stress. So, having a better understanding of the ENS can lead to more effective treatments for both physical and mental conditions.

The new research appears in Nature Neuroscience. In a related commentary, scientist Julia Ganz explains why what the researchers discovered is so important:

“Using single-cell RNA-sequencing to profile the developing and juvenile ENS, the authors discovered a conceptually new model of neuronal diversification in the ENS and establish a new molecular taxonomy of enteric neurons based on a plethora of molecular markers.”

This “neuronal diversification” happens in all living things that have neurons. Similar to stem cells, neurons develop first as more general “outlines” and then form into functional specialties. The human brain has types like sensory and motor neurons. Each type has subtypes. There are so many of these subtypes that scientists don’t even know how to fully categorize them yet.

Neurons of the same superficial type are different in the brain than in the brain stem—let alone in the digestive tract. So, researchers had to start at the very beginning and trace how these neurons develop. They tracked RNA, which determines how DNA is expressed in the cells made by your body, to follow how neurons formed both before and after birth. Some specialties emerge in utero, and some split and form afterward.

To find this new information, the scientists developed a more precise way to separate and identify cells. Ganz explains:

“Using extensive co-staining with established markers, they were able to relate the twelve neuron classes to previously discovered molecular characteristics of functional enteric neuron types, thus classifying the ENCs into excitatory and inhibitory motor neurons, interneurons, and intrinsic primary afferent neurons.”

With a more specific protocol and new information, the researchers were able to confirm and build on the existing body of ENS neuron knowledge. Now, they can work on finding out what each of the 12 ENS neuron types is responsible for, the researchers say.

By isolating the different types and “switching” them on or off using genetic information, scientists can try to identify what’s missing from the function of the mouse ENS. And studying these genes could lead to new treatments that use stem cells or RNA to control the expression of harmful genes.