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A Gut Check for Many Ailments

• By SHIRLEY S. WANG

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What you think is going on in your head may be caused in part by what's happening in your gut.

A growing body of research shows the gut affects bodily functions far beyond digestion. Studies have shown intriguing links from the gut's health to bone formation, learning and memory and even conditions including Parkinson's disease. Recent research found disruptions to the stomach or intestinal bacteria can prompt depression and anxiety—at least in lab rats.

Better understanding the communication between the gut and the brain could help reveal the causes of and treatments for a range of ailments, and provide diagnostic clues for doctors.

Mark McGinnis

New research indicates problems in the gut may cause problems in the brain, just as a mental ailment, such as anxiety, can upset the stomach.

"The gut is important in medical research, not just for problems pertaining to the digestive system but also problems pertaining to the rest of the body," says Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine.

The gut—considered as a single digestive organ that includes the esophagus, stomach and intestines—has its own nervous system that allows it to operate independently from the brain.

This enteric nervous system is known among researchers as the "gut brain." It controls organs including the pancreas and gall bladder via nerve connections. Hormones and neurotransmitters generated in the gut interact with organs such as the lungs and heart.

The Body's Other Mind

• The enteric nervous system, or 'gut brain,' can operate independently of the brain.
• Neurons in the gut produce neurotransmitters also found in the brain, such as serotonin.
• Disruptions to beneficial gut bacteria may affect mood.
• Neurotransmitters made in the gut help control the formation of bone.
• Stimulating gut neurons may help treat obesity and diabetes.

Source: WSJ reporting

Like the brain and spinal cord, the gut is filled with nerve cells. The small intestine alone has 100 million neurons, roughly equal to the amount found in the spinal cord, says Michael Gershon, a professor at Columbia University.

The vagus nerve, which stretches down from the brainstem, is the main conduit between the brain and gut. But the gut doesn't just take orders from the brain.

"The brain is a CEO that doesn't like to micromanage," says Dr. Gershon. The brain receives much more information from the gut than it sends down, he adds.

Many people with psychiatric and brain conditions also report gastrointestinal issues. New research indicates problems in the gut may cause problems in the brain, just as a mental ailment, such as anxiety, can upset the stomach.

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Stanford's Dr. Pasricha and colleagues examined this question in the lab by irritating the stomachs of newborn rats. By the time the animals were eight to 10 weeks old, the physical disturbance had healed, but these animals displayed more depressed and anxious behaviors, such as giving up more quickly in a swimming task, than rats whose stomachs weren't irritated.

Compared to controls, the rats also showed increased sensitivity to stress and produced more of a stress hormone, in a study published in May in a Public Library of Science journal, PLoS One.

Other work, such as that of researchers from McMaster University in Hamilton, Ontario, demonstrated that bacteria in the gut—known as gut flora—play a role in how the body responds to stress. The exact mechanism is unknown, but certain bacteria are thought to facilitate important interactions between the gut and the brain.

Electrically stimulating the vagus nerve has been shown to reduce the symptoms of epilepsy and depression. (One treatment approved by the Food and Drug Administration, made by Cyberonics Inc., is already on the market.)

Exactly why such stimulation works isn't known, experts say, but a similar procedure has been shown in animal studies to help improve learning and memory.

Earlier this month, researchers made a small step toward understanding a gastrointestinal ailment that typically affects children with autism.

In a study of 23 autistic children and nine typically developing kids, a bacterium unique to the intestines of those with autism called Sutterella was discovered.

The results, published online in the journal mBio by researchers at Columbia's school of public health, need to be studied further, but suggest Sutterella may be important in understanding the link between autism and digestive ailments, the authors wrote.

Dr. Gershon, professor of pathology and cell biology at Columbia, has been studying how the gut controls its behavior and that of other organs by investigating the neurotransmitter serotonin.

Low serotonin levels in the brain are known to affect mood and sleep. Several common antidepressants work by raising levels of serotonin in the brain.

Yet about 95% of the serotonin in the body is made in the gut, not in the brain, says Dr. Gershon. Serotonin and other neurotransmitters produced by gut neurons help the digestive track push food through the gut.

Work by Dr. Gershon and others has shown that serotonin is necessary for the repair of cells in the liver and lungs, and plays a role in normal heart development and bone-mass accumulation.

Studying the neurons in the gut also may also help shed light on Parkinson's disease. Some of the damage the disease causes to brain neurons that make the neurotransmitter dopamine also occur in the gut neurons, researchers say.

Researchers are now studying whether gut neurons, which can be sampled through a routine colonoscopy, may help clinicians diagnose and track the disease without invasive brain biopsies, says Pascal Derkinderen, a professor of neurology at Inserm, France's national institute of health.

Write to Shirley S. Wang at shirley.wang@wsj.com