Bacteria in the gut can influence someone’s mood. But scientists haven’t known precisely how those microbes do it. Now research in mice suggests that gut germs may alter the supply of certain molecules to regions of the brain involved in controlling anxiety.
The molecules are called microRNAs. They help keep cells in working order by managing the production of proteins that the cells need to flourish.
Many studies have also suggested that how we think and feel might “be controlled by our gut microbiota,” says Gerard Clarke. This psychiatrist in Ireland at University College Cork is a co-author of the new study.
Gut bacteria can affect whether a mouse shows anxiety-like behaviors, for instance. In people, anxiety might lead to behaviors such as avoiding certain social situations. In mice, a similar state might lead them to avoid bright lights or open spaces. His team’s new findings could help scientists develop new treatments for some mental health problems. Researchers shared their discovery online August 25 in Microbiome.
How they teased out the findings
In people and other animals, the gastrointestinal tract — or GI tract — is crawling with germs. The community of microbes living here is known as the gut microbiota (MY-kroh-by-OH-tuh). The idea of germs camping out inside you might sound gross. But most gut bugs are harmless. Some are even helpful. They might help our bodies use the nutrients in food. Others can help fight off infections or crowd the gut lining so disease-causing germs have a hard time moving in.
Clarke and his team studied two groups of mice. One group included normal mice, whose guts were teeming with bacteria. The other mice were bred in sterile (microbe-free) conditions. Their guts contained no germs. The researchers looked at two brain regions in both groups of mice. These areas are involved in controlling anxiety.
One area is the amygdala (Ah-MIG-duh-lah). The other is the prefrontal cortex. Compared to the brains of normal mice, those with microbe-free guts had more of some types of microRNAs and fewer of others. Later, after the germ-free mice were exposed to microbes, their microRNA levels more closely matched those of normal mice.
The team also examined the same two brain regions in rats whose gut bacteria had been destroyed by antibiotics. These are drugs designed to kill harmful bacteria. These rats either overproduced or underproduced some of the same microRNAs that were off-kilter in bacteria-free mice.
Clarke’s group now suspects that gut bacteria affect their host’s anxiety levels by tampering with microRNAs in specific parts of its brain.
What others make of the new data
“I was a little surprised by the findings — in a positive way,” says Peter Holzer. He suspects “not many people so far have thought about microRNAs in this context.” Holzer, who works in Austria at the Medical University of Graz, was not involved in the study. He does, however, conduct research on how the gut and brain interact. The new findings, he says, head scientists “into a new area in gut-brain research that hasn’t been pursued.”
Researchers still aren’t sure how these bacteria in the brain dial microRNA production up or down. Maybe the microbes send signals along the vagus nerve. That’s a kind of information highway that between the gut and brain. Or perhaps bacteria churn out molecular by-products that start some sort of chemical chain reaction. This might provoke the immune system to produce chemicals that provoke the brain to produce more or less of certain microRNAs.
Alas, Clarke says, figuring out how microbes manipulate the mind from start to finish “is still a work in progress.”
Next, his team wants to see if consuming probiotics and prebiotics might help restore production of microRNAs to normal levels in animals where it currently appears upset. Probiotics are beneficial germs that have been shown to foster gut health. Prebiotics are nutrients that those good germs need to thrive. Clarke and his colleagues would like to see if using these dietary supplements might help ease anxiety. If so, that could lead to new mental-health drugs.
Right now, such drugs may be unrealistic, says Kirsten Tillisch. She’s a gastroenterologist at the University of California, Los Angeles. She was not involved in the new work. “It is just so tempting” to assume that results in mice will hold true in people, she notes. But history shows that “the translation from lab animal to human is hit-and-miss,” she adds. So it may be too early, she cautions, to expect seeing these findings translate into therapies for people.
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amygdala An area deep within the brain and near the temporal lobe. Among other things, the amygdala plays a role in emotions. The term comes from the Greek word for an almond, which this region resembles in shape.
antibiotic A germ-killing substance, usually prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.
anxiety A nervous reaction to events causing excessive uneasiness and apprehension. People with anxiety may even develop panic attacks.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals).
behavior The way something, often a person or other organism, acts towards others, or conducts itself.
bug The slang term for an insect. Sometimes it’s even used to refer to a germ.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
colleague Someone who works with another; a co-worker or team member.
context The setting or circumstances that help explain an event, some statement or some conclusion.
cortex The outermost layer of neural tissue of the brain.
gastroenterology A branch of medicine that deals with the tissues and diseases of the gut — those food-processing organs that include the stomach and intestines. Doctors who specialize in this field are known as gastroenterologists.
gastrointestinal tract The organs — basically the stomach and intestines — that break down and absorb the nutrients needed by the body.
germ Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
host (in biology and medicine) The organism (or environment) in which some other thing resides. Humans may be a temporary host for food-poisoning germs or other infective agents.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
microbiome The scientific term for the entirety of the microorganisms — bacteria, viruses, fungi and more — that take up permanent residence within the body of a human or other animal.
microbiota The microorganisms that live in a particular place or geological period. Scientists call the entirety of the microorganisms in a human or other animal its microbiome.
microRNA Short pieces of RNA that do not code for the production of proteins. Instead, they influence whether and how proteins are produced by interfering with normal production processes.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
nerve A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.
nutrient A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.
online (n.) On the internet. (adj.) A term for what can be found or accessed on
prebiotic An adjective that describes something that existed prior to living things. (in nutrition) A food or nutrient that promotes the growth of beneficial microbes in the gut.
prefrontal cortex A region containing some of the brain’s gray matter. Located behind the forehead, it plays a role in making decisions and other complex mental activities, in emotions and in behaviors.
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
psychiatrist A medical doctor who spends many years learning to study and treat diseases of the human mind. Treatments may consist of talking therapies, prescription drugs or both. This medical field is known as psychiatry.
social (adj.) Relating to gatherings of people; a term for animals (or people) that prefer to exist in groups. (noun) A gathering of people, for instance those who belong to a club or other organization, for the purpose of enjoying each other’s company.
sterile An adjective that means devoid of life — or at least of germs.
supplement (verb) To add to something. (in nutrition) Something taken in pill or liquid form — often a vitamin or mineral — to improve the diet. For instance, it may provide more of some nutrient that is believed to benefit health.
tract A particular, well-defined area. It can be a patch of land, such as the area on which a house is located. Or it can be a bit of real estate in the body. For instance, important parts of an animal’s body will include its respiratory tract (lungs and airways), reproductive tract (gonads and hormone systems important to reproduction) and gastro-intestinal tract (the stomach and intestines — or organs responsible for moving food, digesting it, absorbing it and eliminating wastes).
vagus A large nerve that conducts signals between the gut and brain.