Human evolution: more about the gut's brain (Introduction)

by David Turell , Wednesday, November 22, 2023, 18:32 (157 days ago) @ David Turell

Glia and neurons with vagus nerve and hypothalamus connections:

https://www.quantamagazine.org/in-the-guts-second-brain-key-agents-of-health-emerge-202...

"Breaking down food requires coordination across dozens of cell types and many tissues — from muscle cells and immune cells to blood and lymphatic vessels. Heading this effort is the gut’s very own network of nerve cells, known as the enteric nervous system, which weaves through the intestinal walls from the esophagus down to the rectum. This network can function nearly independently from the brain; indeed, its complexity has earned it the nickname “the second brain.” And just like the brain, it’s made up of two kinds of nervous system cells: neurons and glia.

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"Neuroscientists have increasingly discovered that glia play physiological roles in the brain and nervous system that once seemed reserved for neurons.

"A similar glial reckoning is now happening in the gut. A number of studies have pointed to the varied active roles that enteric glia play in digestion, nutrient absorption, blood flow and immune responses. Others reveal the diversity of glial cells that exist in the gut, and how each type may fine-tune the system in previously unknown ways. One recent study, not yet peer-reviewed, has identified a new subset of glial cells that senses food as it moves through the digestive tract, signaling to the gut tissue to contract and move it along its way.

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" scientists now know that enteric glia are among the first responders to injury or inflammation in gut tissue. They help maintain the gut’s barrier to keep toxins out. They mediate the contractions of the gut that allow food to flow through the digestive tract. Glia regulate stem cells in the gut’s outer layer, and are critical for tissue regeneration. They chat with the microbiome, neurons and immune-system cells, managing and coordinating their functions.

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"Those methods allowed her to get the “first glimpse into the diversity of these glial cells” across all tissues of the duodenum, Scavuzzo said. In June, in a paper published on the biorxiv.org preprint server that has not yet been peer-reviewed, she reported her team’s discovery of six subtypes of glial cells, including one that they named “hub cells.”

"Hub cells express genes for a mechanosensory channel called PIEZO2 — a membrane protein that can sense force and is typically found in tissues that respond to physical touch. Other researchers recently found PIEZO2 present in some gut neurons; the channel allows neurons to sense food in the intestines and move it along. Scavuzzo hypothesized that glial hub cells can also sense force and instruct other gut cells to contract. She found evidence that these hub cells existed not only in the duodenum, but also in the ileum and colon, which suggests they’re likely regulating motility throughout the digestive tract.

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"The experiment offered clear evidence that, in addition to other cells, “glial cells can also sense physical forces” through this mechanosensory channel, said Vassilis Pachnis, the head of the nervous system development and homeostasis laboratory at the Francis Crick Institute. Then, having sensed the change in force, they can shift the activity of neural circuits to trigger muscular contractions. “It’s a wonderful piece of work,” he said.

"Hub cells are only one of many glial subtypes that play functional roles in the gut. Scavuzzo’s new six subtypes, added to those characterized in previous research, together reveal 14 known subgroups of glia across the duodenum, ileum and colon. More are likely to be discovered in coming years, each with new potential to better explain how digestion works and enable researchers to develop treatments for a variety of gastrointestinal disorders.

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"Several years ago, Pachnis and his group found that glia are among the first cell types to respond to injury or inflammation in the mouse gut, and that tampering with enteric glial cells can also create an inflammatory response. In the gut glia seem to perform roles similar to those of true immune cells, Pachnis said, and so their dysfunction can lead to chronic autoimmune disorders and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. “Glial cells definitely play a role in the initiation, the pathogenesis and the progression of the various diseases of the gut,” he said.

"Glia are likely involved because of their central role in communicating between the microbiome, immune cells and other gut cells. Healthy glia strengthen the intestines’ epithelial barrier, a layer of cells that keeps out toxins and pathogens and absorbs nutrients. But in patients with Crohn’s disease, glial cells don’t function properly, resulting in a weaker barrier and inappropriate immune response.

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"These new studies in enteric glia will go a long way toward explaining many gastrointestinal disorders that researchers have struggled to understand and treat, Sharkey said. “I’m really excited to see how these cells have evolved to become central figures in enteric neurobiology over the years.”

"It’s becoming ever clearer that the neuron doesn’t act alone in the enteric system, he added. “It’s got these beautiful partners in glia that really allow it to do its thing in the most efficient and effective way.'”

Comment: all reporting to the hypothalamus. The gut and its nervous system is irreducibly complex and is designed.