The human gut is lined with more than 100 million nerve cells—it’s practically a brain unto itself. And indeed, the gut actually talks to the brain, releasing hormones into the bloodstream that, over the course of about 10 minutes, tell us how hungry it is, or that we shouldn’t have eaten an entire pizza. But a new study reveals the gut has a much more direct connection to the brain through a neural circuit that allows it to transmit signals in mere seconds. The findings could lead to new treatments for obesity, eating disorders, and even depression and autism—all of which have been linked to a malfunctioning gut.

The study reveals “a new set of pathways that use gut cells to rapidly communicate with … the brain stem,” says Daniel Drucker, a clinician-scientist who studies gut disorders at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, who was not involved with the work. Although many questions remain before the clinical implications become clear, he says, “This is a cool new piece of the puzzle.”

In 2010, neuroscientist Diego Bohórquez of Duke University in Durham, North Carolina, made a startling discovery while looking through his electron microscope. Enteroendocrine cells, which stud the lining of the gut and produce hormones that spur digestion and suppress hunger, had footlike protrusions that resemble the synapses neurons use to communicate with each other. Bohórquez knew the enteroendocrine cells could send hormonal messages to the central nervous system, but he also wondered whether they could “talk” to the brain using electrical signals, the way that neurons do. If so, they would have to send the signals through the vagus nerve, which travels from the gut to the brain stem.

He and colleagues injected a fluorescent rabies virus, which is transmitted through neuronal synapses, into the colons of mice and waited for the enteroendocrine cells and their partners to light up. Those partners turned out to be to vagal neurons, the researchers report today in Science.

In a petri dish, enteroendocrine cells reached out to vagal neurons and formed synaptic connections with each other. The cells even gushed out glutamate, a neurotransmitter involved in smell and taste, which the vagal neurons picked up on within 100 milliseconds—faster than an eyeblink.

That’s much faster than hormones can travel from the gut to the brain through the bloodstream, Bohórquez says. Hormones’ sluggishness may be responsible for the failures of many appetite suppressants that target them, he says. The next step is to study whether this gut-brain signaling provides the brain with important information about the nutrients and caloric value of the food we eat, he says.

There are some obvious advantages to superfast gut-brain signaling, such as detecting toxins and poison, but there may be other perks to sensing the contents of our guts in real time, he says. Whatever those are, there’s a good chance the benefits are ancient—gut sensory cells date back to one of the first multicellular organisms, a flat creature called Trichoplax adhaerens, which arose roughly 600 million years ago.

Additional clues about how gut sensory cells benefit us today lie in a separate study, published today in Cell. Researchers used lasers to stimulate the sensory neurons that innervate the gut in mice, which produced rewarding sensations the rodents worked hard to repeat. The laser stimulation also increased levels of a mood-boosting neurotransmitter called dopamine in the rodents’ brains, the researchers found.

Combined, the two papers help explain why stimulating the vagus nerve with electrical current can treat severe depression in people, says Ivan de Araujo, a neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City, who led the Cell study. The results may also explain why, on a basic level, eating makes us feel good. “Even though these neurons are outside the brain, they perfectly fit the definition of reward neurons” that drive motivation and increase pleasure, he says.

From Johns Hopkins Medicine...

The Brain-Gut Connection

Anxiety and depression have been thought to contribute to gastro conditions like irritable bowel syndrome (IBS). A Johns Hopkins expert explains how what’s going on in your gut could be affecting your brain

f you’ve ever “gone with your gut” to make a decision or felt “butterflies in your stomach” when nervous, you’re likely getting signals from an unexpected source: your second brain. Hidden in the walls of the digestive system, this “brain in your gut” is revolutionizing medicine’s understanding of the links between digestion, mood, health and even the way you think.

Scientists call this little brain the enteric nervous system (ENS). And it’s not so little. The ENS is two thin layers of more than 100 million nerve cells lining your gastrointestinal tract from esophagus to rectum.

What Does Your Gut’s Brain Control?

Unlike the big brain in your skull, the ENS can’t balance your checkbook or compose a love note. “Its main role is controlling digestion, from swallowing to the release of enzymes that break down food to the control of blood flow that helps with nutrient absorption to elimination,” explains Jay Pasricha, M.D., director of the Johns Hopkins Center for Neurogastroenterology, whose research on the enteric nervous system has garnered international attention. “The enteric nervous system doesn’t seem capable of thought as we know it, but it communicates back and forth with our big brain—with profound results.”

The ENS may trigger big emotional shifts experienced by people coping with irritable bowel syndrome (IBS) and functional bowel problems such as constipation, diarrhea, bloating, pain and stomach upset. “For decades, researchers and doctors thought that anxiety and depression contributed to these problems. But our studies and others show that it may also be the other way around,” Pasricha says. Researchers are finding evidence that irritation in the gastrointestinal system may send signals to the central nervous system (CNS) that trigger mood changes.

“These new findings may explain why a higher-than-normal percentage of people with IBS and functional bowel problems develop depression and anxiety,” Pasricha says. “That’s important, because up to 30 to 40 percent of the population has functional bowel problems at some point.”

New Gut Understanding Equals New Treatment Opportunities

This new understanding of the ENS-CNS connection helps explain the effectiveness of IBS and bowel-disorder treatments such as antidepressants and mind-body therapies like cognitive behavioral therapy (CBT) and medical hypnotherapy. “Our two brains ‘talk’ to each other, so therapies that help one may help the other,” Pasricha says. “In a way, gastroenterologists (doctors who specialize in digestive conditions) are like counselors looking for ways to soothe the second brain.”

Gastroenterologists may prescribe certain antidepressants for IBS, for example—not because they think the problem is all in a patient’s head, but because these medications calm symptoms in some cases by acting on nerve cells in the gut, Pasricha explains. “Psychological interventions like CBT may also help to “improve communications” between the big brain and the brain in our gut,” he says.

Still More to Learn About Mind-Gut Link

Pasricha says research suggests that digestive-system activity may affect cognition (thinking skills and memory), too. “This is an area that needs more research, something we hope to do here at Johns Hopkins,” he says.

Another area of interest: Discovering how signals from the digestive system affect metabolism, raising or reducing risk for health conditions like type 2 diabetes. “This involves interactions between nerve signals, gut hormones and microbiota—the bacteria that live in the digestive system,” Pasricha says.

https://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection

Irritable bowel syndrome

Overview

Irritable bowel syndrome (IBS) is a common disorder that affects the large intestine. Signs and symptoms include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or both. IBS is a chronic condition that you'll need to manage long term.

Only a small number of people with IBS have severe signs and symptoms. Some people can control their symptoms by managing diet, lifestyle and stress. More-severe symptoms can be treated with medication and counseling.

IBS doesn't cause changes in bowel tissue or increase your risk of colorectal cancer.

Symptoms

The signs and symptoms of IBS vary. The most common include:

Abdominal pain, cramping or bloating that is typically relieved or partially relieved by passing a bowel movement
Excess gas
Diarrhea or constipation — sometimes alternating bouts of diarrhea and constipation
Mucus in the stool

Most people with IBS experience times when the signs and symptoms are worse and times when they improve or even disappear completely.

When to see a doctor

See your doctor if you have a persistent change in bowel habits or other signs or symptoms of IBS. They may indicate a more serious condition, such as colon cancer. More-serious signs and symptoms include:

Weight loss
Diarrhea at night
Rectal bleeding
Iron deficiency anemia
Unexplained vomiting
Difficulty swallowing
Persistent pain that isn't relieved by passing gas or a bowel movement

Causes

The precise cause of IBS isn't known. Factors that appear to play a role include:

Muscle contractions in the intestine. The walls of the intestines are lined with layers of muscle that contract as they move food through your digestive tract. Contractions that are stronger and last longer than normal can cause gas, bloating and diarrhea. Weak intestinal contractions can slow food passage and lead to hard, dry stools.
Nervous system. Abnormalities in the nerves in your digestive system may cause you to experience greater than normal discomfort when your abdomen stretches from gas or stool. Poorly coordinated signals between the brain and the intestines can cause your body to overreact to changes that normally occur in the digestive process, resulting in pain, diarrhea or constipation.
Inflammation in the intestines. Some people with IBS have an increased number of immune-system cells in their intestines. This immune-system response is associated with pain and diarrhea.
Severe infection. IBS can develop after a severe bout of diarrhea (gastroenteritis) caused by bacteria or a virus. IBS might also be associated with a surplus of bacteria in the intestines (bacterial overgrowth).
Changes in bacteria in the gut (microflora). Microflora are the "good" bacteria that reside in the intestines and play a key role in health. Research indicates that microflora in people with IBS might differ from microflora in healthy people.

Triggers

Symptoms of IBS can be triggered by:

Food. The role of food allergy or intolerance in IBS isn't fully understood. A true food allergy rarely causes IBS. But many people have worse IBS symptoms when they eat or drink certain foods or beverages, including wheat, dairy products, citrus fruits, beans, cabbage, milk and carbonated drinks.
Stress. Most people with IBS experience worse or more frequent signs and symptoms during periods of increased stress. But while stress may aggravate symptoms, it doesn't cause them.
Hormones. Women are twice as likely to have IBS, which might indicate that hormonal changes play a role. Many women find that signs and symptoms are worse during or around their menstrual periods.

Risk factors

Many people have occasional signs and symptoms of IBS. But you're more likely to have the syndrome if you:

Are young. IBS occurs more frequently in people under age 50.
Are female. In the United States, IBS is more common among women. Estrogen therapy before or after menopause also is a risk factor for IBS.
Have a family history of IBS. Genes may play a role, as may shared factors in a family's environment or a combination of genes and environment.
Have a mental health problem. Anxiety, depression and other mental health issues are associated with IBS. A history of sexual, physical or emotional abuse also might be a risk factor.

Complications

Chronic constipation or diarrhea can cause hemorrhoids.

In addition, IBS is associated with:

Poor quality of life. Many people with moderate to severe IBS report poor quality of life. Research indicates that people with IBS miss three times as many days from work as do those without bowel symptoms.
Mood disorders. Experiencing the signs and symptoms of IBS can lead to depression or anxiety. Depression and anxiety also can make IBS worse.

Prevention

Finding ways to deal with stress may help prevent or ease symptoms of IBS. Consider trying:

Counseling. A counselor can help you learn to modify or change your responses to stress. Studies have shown that psychotherapy can provide significant and long-lasting reduction of symptoms.
Biofeedback. Electrical sensors help you receive information (feedback) on your body's functions. The feedback helps you focus on making subtle changes, such as relaxing certain muscles, to ease symptoms.
Progressive relaxation exercises. These exercises help you relax muscles in your body, one by one. Start by tightening the muscles in your feet, then concentrate on slowly letting all of the tension go. Next, tighten and relax your calves. Continue until the muscles in your body, including those in your eyes and scalp, are relaxed.
Mindfulness training. This stress-reduction technique helps you focus on being in the moment and letting go of worries and distractions.

https://www.mayoclinic.org/diseases-conditions/irritable-bowel-syndrome/symptoms-causes/syc-20360016

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