Our guts hold a kind of brain, known as the enteric nervous system; it is a network of neurons that extends throughout the walls of the gastrointestinal tract. This neural network can also function independently of the brain, and it has many important roles in digestion, immunity, and the control of blood flow. Scientists have now identified three kinds of neurons that are linked to projections from the intestinal wall, called villi. This research has indicated that fluid balance in the gut is controlled in a previously unrecognized way. The findings have been reported in Nature Neuroscience, and they could inform the study and treatment of bowel disorders.
In this work, the investigators analyzed a portion of the enteric nervous system called the submucosal nerve layer to learn more about it. This revealed three novel types of neurons, one of which can sense what's in the intestine.
"We have identified the types of nerve cells embedded in the innermost part of the intestine, closest to the villi, in the so-called submucosal nerve layer. Contrary to previous studies, we found that this layer contains three types of nerve cells." One of these neurons can sense the contents of the intestine and signal to other neurons to respond in a way that, "optimizes nutrient absorption and fluid balance," said senior study author Ulrika Marklund, Associate Professor at the Karolinska Institutet.
The researchers used a mouse model to isolate, remove, and sequence the DNA of intestinal cells individually; this identified the genes being expressed in those cells. The investigators also utilized genetically modified mice to visualize the signaling among neurons and the intestinal epithelium.
All of these cell types are linked to one another and the intestinal villi. "This opens up the possibility of previously unknown neural networks that could regulate fluid balance and blood flow, which may be highly relevant for conditions like constipation and diarrhea, and thus also associated diseases such as IBS and IBD," said Marklund.
The work also revealed that these newly identified cell types mature in a stepwise fashion during embryonic development. This process is similar to one in the gut's outer layer of neurons, but is unlike any known to be involved in brain cell development. The researchers suggested that neurons in the enteric nervous system may all follow this type of stepwise maturation process.
The investigators want to learn more about how these novel cell types are affected by various signals, like mechanical pressure from intestinal contents; or what various molecules they release and what their impact is. It may one day be possible to treat various bowel diseases like IBD or IBS by targeting these cells.
Sources: Karolinska Institutet, Nature Neuroscience