What organ is responsible for serotonin?

Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota

Date: September 6, 2019 Source: University of California — Los Angeles Summary: A new study in mice strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines. Share:

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A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines.

Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.

The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.

«Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,» said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.

Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.

That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?

In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.

If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinis. They found the bacterium transported significantly less serotonin.

The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.

«Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,» Fung said. «Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.»

The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. «For the future,» Hsiao said, «we want to learn whether microbial interactions with antidepressants have consequences for health and disease.» Hsiao wrote a blog post for the journal about the new research.

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      Serotonin Deficiency – What Causes it and How To Help

      

      Serotonin is one of the most widely recognized of all neurotransmitters. It is intricately involved in numerous core physical processes such as the regulation of sleep, appetite, and aggression. Serotonin is also a key player in mood, anxiety, fear and a general sense of well-being. Imbalances in serotonin, particularly relative to norepinephrine and dopamine, are common causes of certain types of depression. Antidepressants that block serotonin’s re-uptake back into serotonin neurons are among the most common of all classes of medications prescribed.

      Serotonin deficiency is a common contributor to mood problems. Some feel it is an epidemic in the United States. Serotonin is key to our feelings of happiness and very important for our emotions because it helps defend against both anxiety and depression. Many of the current biochemical theories of depression focus on the biogenic amines, which are a group of chemical compounds important in neurotransmission—most importantly norepinephrine, serotonin and, to a lesser extent, dopamine, acetylcholine and epinephrine.

      What Causes or Contributes to Serotonin Deficiency?
      

      

      Many life stressors can lead to low serotonin:

      • Prolonged periods of stress can deplete serotonin levels. Our fast-paced, fast food society greatly contributes to these imbalances.
      • Genetic factors, faulty metabolism, and digestive issues can impair the absorption and breakdown of our food which reduces our ability to build serotonin.
      • Poor Diet. Neurotransmitters are made in the body from proteins. Also required are certain vitamins and minerals called “co-factors”. If your nutrition is poor and you do not take in enough protein, vitamins, or minerals to build the neurotransmitters, a neurotransmitter imbalance develops. We really do think and feel what we eat.
      • Toxic substances like heavy metals, pesticides, drug use, and some prescription drugs can cause permanent damage to the nerve cells that make serotonin and other neurotransmitters.
      • Certain drugs and substances such as caffeine, alcohol, nicotine, NutraSweet, antidepressants, and some cholesterol-lowering medications deplete serotonin and other neurotransmitter levels.
      • Hormone changes cause low levels of serotonin and neurotransmitter imbalances.
      • Lack of sunlight contributes to low serotonin levels.

      What Are The Symptoms of Serotonin Deficiency?

      You may have a shortage of serotonin if you have a sad depressed mood, low energy, negative thoughts, feel tense and irritable, crave sweets, and have a reduced interest in sex. Other serotonin-related disorders include:

      • Depression
      • Anxiety
      • Panic Attacks
      • Insomnia
      • Irritable bowel
      • PMS/ Hormone dysfunction
      • Fibromyalgia
      • Obesity
      • Eating disorders
      • Obsessions and Compulsions
      • Muscle pain
      • Chronic Pain
      • Alcohol abuse
      • Migraine Headaches

      How Do I Know if Serotonin is Deficient?

      Neurotransmitter testing, Questionnaires, and blood testing can help determine if you might have a serotonin deficiency. Certain tests can determine if you have normal levels of the precursors and co-factor vitamins and minerals needed for the brain to produce serotonin. Additionally, hormones such as Adrenal, Thyroid, and Estrogen levels can affect serotonin levels, and may explain why some women have premenstrual and menopausal mood problems.

      How Can You Raise Serotonin Levels Naturally?

      Prescription drugs such as Prozac, Zoloft, Paxil, and Lexapro are classified as serotonin reuptake inhibitors, or (SSRIs). They help to keep more of the serotonin your brain is making in circulation. They do not, however, increase your brain’s supply of serotonin. Some studies, in fact, indicate that over time they may actually accelerate your turnover of serotonin, thereby making your serotonin deficiency worse. They are used for a wide variety of symptoms such as depression, panic attacks, anxiety, PTSD, obsessions, and compulsions. There are also serotonin/norepinephrine reuptake inhibitors (SNRIs) such as Effexor and Cymbalta that keep more serotonin and norepinephrine in circulation. Again, such agents do not help you build more neurotransmitters.

      Nutrient therapies such as Targeted Amino Acid Therapy naturally increase the levels of neurotransmitters that a person has been found to be deficient in. 5-Hydroxytryptophan and Tryptophan are widely known for their ability to help depressive symptoms by raising serotonin levels in the brain. Numerous clinical trials have studied the efficacy of 5-HTP for treating depression. One compared 5-HTP to the antidepressant drug fluvoxamine and found 5-HTP to be equally effective.

      It can be used alone or in combination with medication to keep dosages low and to prevent the “poop out” many people experience with medication.

      • tryptophan —> 5-HTP —> serotonin

      Herbal remedies, such as St. John’s Wort, are available to alleviate symptoms of depression and anxiety. Some work in a similar way to the SSRI antidepressants.

      What Are Things You Can Do To Increase Your Serotonin Levels and Improve Overall Health?

      Here are some lifestyle changes that you can do to help increase your serotonin levels

      • Exercise at least 30 minutes three times a week
      • Walking, yoga, stretching
      • Get plenty of sunlight
      • Drink 6-8 glasses of water daily
      • Prayer and meditation
      • Eat at least three meals per day. Skipping meals promotes high stress and low energy. Eat protein with every meal. Eat complex carbohydrates such as brown rice. Avoid sugar, junk food, white pasta, white rice, white bread, cookies and cake. No caffeine, alcohol, or NutraSweet (aspartame). NutraSweet can be toxic to your brain. Alcohol can worsen depression, anxiety and sleep problems.

      The Brain-Gut Connection

      

      

      If 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.

      Can Probiotics Improve Your Mood?

      

      By now, we know that a healthy diet is important for physical well-being. Researchers are studying whether probiotics — live bacteria that are safe to eat — can improve gastrointestinal health and your mood.

      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.

      #TomorrowsDiscoveries: A Different Approach to Treating Psychiatric Disorders | Atsushi Kamiya, M.D.

      Dr. Atsushi Kamiya studies how genetic and environmental factors cause problems in brain function, using this knowledge to prevent and treat cognitive and mood disorders.

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