The brain and gut are connected, but the exact nature of that connection is still a mystery. Research suggests, however, that the better we treat our guts, the healthier our brains will be, and vice versa.
Encompassing all the organs that process food, the gut consists of the mouth, esophagus, stomach, pancreas, liver, gallbladder, small intestine, and large intestine, which includes the colon and rectum. Scientists have been studying the gut components to better understand how they may put people at risk for Alzheimer's disease, multiple sclerosis, Parkinson's disease, and other neurologic disorders.
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“The notion of gastrointestinal health, and thus normal gut flora, may be as old as medicine itself,” says Michael G. Schlossmacher, MD, endowed chair in neurodegeneration at Canada's Ottawa Hospital Research Institute and co-director of the Parkinson Research Consortium.
Living within the gut are trillions of microorganisms, including bacteria, fungi, protozoa, and viruses. These microbes aid multiple bodily functions, like breaking down food, producing vitamins, responding to pathogens, and helping the body absorb nutrients. The genes that produce these microorganisms—which also live in saliva, skin, and other body parts—and the microorganisms themselves are collectively known as the microbiome. Various factors, including genetics, lifestyle, diet, environmental exposures, and use of antibiotics, likely influence the microbiome's composition.
Research in this area is so promising that the federal government funds it. In 2008, the National Institutes of Health launched the Human Microbiome Project, which supports inquiry into the impact of microorganisms on health. One of its goals is to create a repository of data on microorganisms for researchers' reference.
Investigators examining samples from the gut have theorized that microbe balance is important in more than just gastrointestinal disorders, says Dr. Schlossmacher. For example, having too much of one kind of bacteria and not enough of another could lead to changes in permeability, often referred to as “leaky gut,” a condition being studied in the context of Parkinson's disease. Although an unhealthy microbiome is thought to cause many different diseases, scientists have yet to find an explanation for how it harms brain cells, Dr. Schlossmacher says.
Millions of nerve cells lining the gut form what's known as the enteric nervous system. “The gut is called the second brain for a reason,” says Kathleen M. Shannon, MD, FAAN, professor and chair of neurology at the University of Wisconsin School of Medicine and Public Health in Madison. “There are so many nervous system cells in the enteric nervous system. It's also really important in communicating with the brain.”
Exactly how the brain and gut communicate is not completely understood, but the communication likely goes in both directions, Dr. Shannon says. It may happen through nerve cells and cytokines—proteins released by cells of the immune system. Operating like a freeway within this communication network is the vagus nerve, which extends from the brain stem to the abdomen and helps regulate digestion. Researchers believe that understanding brain-gut communication could help prevent disease, as it's possible that diseases once thought to begin in the brain actually originate in the gut.
Several theories seek to explain how gut health affects the brain. One involves inflammation—the immune system's response to infection or injury. When the body is invaded by a virus or harmful bacteria, the immune system attacks the invader and repairs cells, and the resultant increase in blood flow and chemicals released into cells produces inflammation. If this occurs without an invading agent, it can damage tissue. A possible cause of such inflammation is the modern diet, which can be heavy on refined carbohydrates, sugars, and processed foods rather than unprocessed and whole grains, fruits, vegetables, nuts, and fish. But the microbiome has not evolved as much as people's eating habits, according to Ali Keshavarzian, MD, director of the Rush Center for Integrated Microbiome and Chronobiology Research in Chicago, so the gut may mount an inflammatory response because it senses certain foods as invaders.
“Poor diet, or sustained stress or poor sleep, can lead to changes in the microbiota, which creates an inflammatory state in the gut that causes leakiness,” Dr. Keshavarzian says. “The inflammatory bacteria-derived molecules can travel throughout the body and reach the brain. In people genetically predisposed to a neurologic disorder, inflammation in the gut may trigger the disease.”
Possible Parkinson's Link
In a study published in 2011 in the journal PLOS One, Dr. Keshavarzian, Dr. Shannon, and colleagues reported that people with Parkinson's disease had more permeable guts than those without it. And people with leaky guts also show signs of inflammation in the intestines and the bloodstream. It is thought that inflammation outside the brain may subsequently lead to inflammation in the brain and incite a degenerative process there.
“Certain bacteria could stimulate and activate immune cells that reside in the intestines or liver. If a person has a leaky gut, those cells can leak into the circulation and activate immune cells. If that activation is sustained enough, it could lead to disease,” says Dr. Keshavarzian, who is currently studying whether modifying bacteria in the gut could improve gut health and brain health.
As early as 2003, an idea was proposed in the Journal of Neural Transmission by researchers at the University of Frankfurt in Germany that some cases of Parkinson's disease may be caused by an unknown pathogen that enters the gastrointestinal tract and makes its way to the central nervous system.
“No one is suggesting that one bacterium or type of gut inflammation triggers central nervous system damage specific to Parkinson's,” Dr. Shannon says. “The thought is that it all relates to a combination of genetic and environmental influences.” Inflammation originating in the gut might be a trigger for Parkinson's disease in some people, she says.
Many people with Parkinson's disease experience constipation, sometimes decades before developing motor symptoms. This is one clue that the gut might be involved, says Silke Appel-Cresswell, MD, associate professor of neurology at the University of British Columbia in Vancouver. “The underlying pathological changes that trigger constipation and how those changes move to the brain and cause slowness and tremor are the subject of intense research,” she says.
More research is needed on constipation as a possible risk factor for Parkinson's, but physicians may want to screen for it during routine checkups, says Dr. Schlossmacher. “Drinking more water and eating more fruit and vegetables will not only improve your general health, it may also help reduce the risk of Parkinson's,” he says. In a study of more than 6,700 men ages 51 to 75, published in Neurology in 2001, researchers found that those with chronic constipation were four times as likely to develop Parkinson's disease as men who were not constipated.
The Gut and Dementia
Scientists are also exploring the link between the gut and other neurologic disorders. In a 2014 study in Neurology, researchers showed that the 61 patients with multiple sclerosis had higher levels of microorganisms associated with inflammation in their stool samples than the 43 study participants without the disease. In 2019, a study published in Alzheimer's & Dementia examined bile acids in the guts of 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 with Alzheimer's disease. The people with Alzheimer's disease had lower concentrations of a primary bile acid than people who were not cognitively impaired.
But solid evidence is lacking on whether disruption in the gut actually causes disease and whether the gut damage is reversible or permanent. And there's a chicken-and-egg question: Does an unhealthy gut microbiome cause disease or does disease cause an unhealthy gut microbiome?
While experts are not sure if a healthy gut can prevent neurologic disease or improve symptoms, some research suggests that physical activity and adequate sleep—among other habits that promote general health—benefit the gut and brain as well, says Dr. Keshavarzian. “But more rigorous studies are needed to substantiate that.”
Quitting smoking and cutting back on alcohol also may be helpful, says Dr. Schlossmacher. Smoking can change the oral and gastrointestinal flora as well as stomach acidity, and drinking too much alcohol could damage intestinal mucosa, he says.
Probiotic supplements may help keep a balance of good and bad bacteria in the gut. “We don't yet know which bacteria species in the gut they will help,” Dr. Shannon says. “Clinical trials are needed in this area.”
“The only thing we can reasonably endorse is eating a healthy diet,” says Jay Pasricha, MBBS, MD, director of the Johns Hopkins Center for Neurogastroenterology in Baltimore, who suggests reducing consumption of red meat and sugar and eating more high-fiber foods. “Think moderation rather than complete restriction,” he says.
“Epidemiological studies support the notion that diet can affect brain health,” Dr. Keshavarzian says, explaining that in societies in which people tend to eat mostly plants, neurologic disease is much less common than in communities with diets that are typically sugary, fatty, and low in fiber.
“The more diverse the range of microorganisms in the gut, the better,” says Alberto Espay, MD, FAAN, director of the University of Cincinnati's James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders. That means eating a variety of foods, mostly plant-based, and staying away from processed carbohydrates.
In particular, the Mediterranean diet—which favors whole grains, legumes, produce, and olive oil—has been shown to reduce “multiple systemic problems,” says Dr. Shannon. Observational studies involving thousands of people have found that the Mediterranean style of eating is associated with a longer life expectancy and reduced risk of cardiovascular disease. The British Medical Journal reported in 2014 that a study analyzing blood samples and food frequency questionnaires from more than 4,600 women found that those who tended to adhere to the Mediterranean diet were more likely to have longer telomeres—sections of DNA that protect chromosomes from damage.
Despite the unknowns, many physicians are leaning toward the idea that a good diet will help improve brain health. “I hope that in three to five years my colleagues and I will provide direct evidence to support that recommendation,” Dr. Keshavarzian says.
Eating the Mediterranean Way
Rather than making wholesale changes to your eating habits, start with small steps toward adopting the Mediterranean diet. Instead of cooking with corn oil, use olive oil. Swap white bread for whole grain. At your next barbecue, skip the burger and opt for grilled chicken. For breakfast, say no to a muffin and make an egg frittata with vegetables and feta cheese.
At every meal, there's an opportunity to make different choices: fresh fruit instead of cookies, unsalted nuts instead of french fries, sunflower seeds instead of croutons, fish over pork chops, to name a few.
In general, try to eat whole grains, olive oil, fruits, and vegetables every day. Incorporate fish and shellfish, poultry, eggs, cheese, yogurt, beans, and nuts several times a week, and reserve red meat for rare occasions.
Try one of the Mediterranean-style recipes developed by Linda Monastra, a chef and graduate of the National Gourmet Institute in New York City.
