Gut communicates with the entire brain through cross-talking neurons

April 2, 2020

Science Daily/University of Illinois College of Agricultural, Consumer and Environmental Sciences

You know that feeling in your gut? We think of it as an innate intuition that sparks deep in the belly and helps guide our actions, if we let it. It's also a metaphor for what scientists call the "gut-brain axis," a biological reality in which the gut and its microbial inhabitants send signals to the brain, and vice versa.

It's not a surprise that the brain responds to signals in the gut, initiating motor functions involved with digestion. Directed by the brainstem, these types of basic biological actions are largely automatic. But what if the higher brain -- the thinking, emotional centers -- were influenced by signals in the gut, too? New University of Illinois research in rats shows the entire brain responds to the gut, specifically the small intestine, through neuronal connections.

To map the connections, researchers inserted neuron-loving viruses in the rats' small intestines and traced the viruses as they moved from neuron to neuron along the Vagus and spinal nerves and throughout the brain. The idea was virus movement mimicked the movement of normal signals through neurons from the gut to the brain and back.

"We saw a lot of connections in the brainstem and hindbrain regions. We knew these regions are involved in sensing and controlling the organs of the body, so there weren't any big surprises there. But things got more interesting as the viruses moved farther up into parts of the brain that are usually considered emotional centers or learning centers, cognitive places. They have all these multifaceted functions. So thinking about how information from the small intestine might be nudging those processes a little bit is really cool," says Coltan Parker, doctoral student in the Neuroscience Program at Illinois and lead author on a study published in Autonomic Neuroscience: Basic and Clinical.

The study represents the first complete map of neuronal connections between the small intestine -- what Parker and his co-authors call an "underloved" part of the digestive system -- and the entire brain. The involvement of cognitive and emotional centers hints at how the thinking brain sometimes overrides our feeling of being full, provides fodder to explore relationships between depression and digestive troubles, and more.

"Now we're actually finding the neuro-anatomy that might be involved in that 'feeling in your gut,'" says Megan Dailey, study co-author and program administrator in the College of Agricultural, Consumer and Environmental Sciences at Illinois.

In addition to showing just how extensive the connections are between the small intestine and the brain, the study uncovered a rarely documented feature of the neurons themselves.

Scientists have long assumed sensations from the gut, or anywhere in the body, traveled to the brain along one set of neurons (the sensory neurons), with instructions from the brain traveling back along a separate set of neurons (the motor neurons). But in their mapping study, Illinois researchers discovered some of the neurons -- about half -- were transmitting both sensory and motor signals.

They were capable of cross-talk within the same neuron.

"From the cortex to the brainstem, in pretty much every region we investigated, there was that 50% overlap of sensory-motor signals. It was throughout the brain, consistently," says study co-author Elizabeth Davis. Davis is a 2018 graduate of the Illinois Neuroscience Program and is currently studying as a postdoctoral scholar at the University of Southern California.

The same pattern -- 50% of neurons having both sensory and motor signaling capabilities -- had only been shown one other time, in a study mapping neuronal connections between fat tissue and the brain. The researchers point out new evidence of the same crosstalk pattern could suggest a general architecture of neuronal networks between the body and brain.

"This study shows that sensorimotor feedback loops are abundant across all levels of the brain. Up until now, it has really been unknown how information in the small intestine, about nutrients or anything else, can get up to the brain and affect cognitive-emotional processes, and then how those processes can come back down and affect the gut," Parker says. "With more research, we may finally begin to understand how hunger makes us 'hangry,' or how a stressful day becomes an irritable bowel."

https://www.sciencedaily.com/releases/2020/04/200402155733.htm

Gut instincts: Researchers discover first clues on how gut health influences brain health

October 23, 2019

Science Daily/Weill Cornell Medicine

New cellular and molecular processes underlying communication between gut microbes and brain cells have been described for the first time by scientists at Weill Cornell Medicine and Cornell's Ithaca campus.

Over the last two decades, scientists have observed a clear link between autoimmune disorders and a variety of psychiatric conditions. For example, people with autoimmune disorders such as inflammatory bowel disease (IBD), psoriasis and multiple sclerosis may also have depleted gut microbiota and experience anxiety, depression and mood disorders. Genetic risks for autoimmune disorders and psychiatric disorders also appear to be closely related. But precisely how gut health affects brain health has been unknown.

"Our study provides new insight into the mechanisms of how the gut and brain communicate at the molecular level," said co-senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine. "No one yet has understood how IBD and other chronic gastrointestinal conditions influence behavior and mental health. Our study is the beginning of a new way to understand the whole picture."

For the study, published Oct. 23 in Nature, the researchers used mouse models to learn about the changes that occur in brain cells when gut microbiota are depleted. First author Dr. Coco Chu, a postdoctoral associate in the Jill Roberts Institute for Research in Inflammatory Bowel Disease, led a multidisciplinary team of investigators from several departments across Weill Cornell Medicine, Cornell's Ithaca campus, Boyce Thompson Institute, Broad Institute at MIT and Harvard, and Northwell Health with specialized expertise in behavior, advanced gene sequencing techniques and the analysis of small molecules within cells.

Mice treated with antibiotics to reduce their microbial populations, or that were bred to be germ-free, showed a significantly reduced ability to learn that a threatening danger was no longer present. To understand the molecular basis of this result, the scientists sequenced RNA in immune cells called microglia that reside in the brain and discovered that altered gene expression in these cells plays a role in remodeling how brain cells connect during learning processes. These changes were not found in microglia of healthy mice.

"Changes in gene expression in microglia could disrupt the pruning of synapses, the connections between brain cells, interfering with the normal formation of new connections that should occur through learning," said co-principal investigator Dr. Conor Liston, an associate professor of neuroscience in the Feil Family Brain & Mind Research Institute and an associate professor of psychiatry at Weill Cornell Medicine.

The team also looked into chemical changes in the brain of germ-free mice and found that concentrations of several metabolites associated with human neuropsychiatric disorders such as schizophrenia and autism were changed. "Brain chemistry essentially determines how we feel and respond to our environment, and evidence is building that chemicals derived from gut microbes play a major role," said Dr. Frank Schroeder, a professor at the Boyce Thompson Institute and in the Chemistry and Chemical Biology Department at Cornell Ithaca.

Next, the researchers tried to reverse the learning problems in the mice by restoring their gut microbiota at various ages from birth. "We were surprised that we could rescue learning deficits in germ-free mice, but only if we intervened right after birth, suggesting that gut microbiota signals are required very early in life," said Dr. Liston. "This was an interesting finding, given that many psychiatric conditions that are associated with autoimmune disease are associated with problems during early brain development."

"The gut-brain axis impacts every single human being, every day of their lives," said Dr. Artis. "We are beginning to understand more about how the gut influences diseases as diverse as autism, Parkinson's disease, post-traumatic stress disorder and depression. Our study provides a new piece of understanding of how the mechanisms operate."

"We don't know yet, but down the road, there is a potential for identifying promising targets that might be used as treatments for humans in the future," Dr. Liston said. "That's something we will need to test going forward."

https://www.sciencedaily.com/releases/2019/10/191023172106.htm