How Much Serotonin Is Made In The Gut


Ibs And Mental Illness

Gut Bacteria and Brain Function: The Science of Serotonin Production with Zach Bush, MD

IBS and its symptoms largely impact daily activities and body image and are a cause of worry to patients. IBS is usually related to disgrace, and patients are stigmatized as frequent fliers or somatizers. Cognitive behavior therapy could be a psychological or talking therapy, which can be significantly helpful for patients with IBS. Fifty to 90% of IBS patients have a co-existing psychological condition, reminiscent of anxiety or depression . Researchers have found high levels of reported sexual and emotional abuse among patients with IBS. Somatization disorder , a psychiatric disorder has a prevalence of around 25% in patients with IBS, compared with around 1% among the overall population .

Table 1 IBS Patients with co-existing Mental illness studies

What Does Your Guts Brain Control

Unlike the big brain in your skull, the ENS cant 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 doesnt seem capable of thought as we know it, but it communicates back and forth with our big brainwith profound results.

The ENS may trigger big emotional shifts experienced by people coping with irritable bowel syndrome 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 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. Thats 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 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 are like counselors looking for ways to soothe the second brain.

Gastroenterologists may prescribe certain antidepressants for IBS, for examplenot because they think the problem is all in a patients 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.

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How Does The Gut Play A Role In Producing Serotonin

So remember the overwhelming amount of serotonin that comes directly from the gut? Heres why having a healthy gut is the key to happiness .

For all of its importance to mental wellbeing, you might expect that the brain is where we find most of the body’s serotonin, but it’s not. In fact, the gut contains the vast majority of the serotonin in our body. To get technical, serotonin is produced in the enterochromaffin cells that line the digestive tract. And with this in mind at this current time, it is believed that our gut bacteria can both, directly and indirectly, influence serotonin levels.

We know that fluctuations in serotonin levels, or for those who struggle to produce enough, mental health disorders like depression and anxiety can become very real. But serotonin has also been linked to physiological disorders like IBS, although it is not yet known the role that the two conditions may influence each other. But what can be said for certain is that knowing your gut is such an important site for this key part of life, you need to make conscious steps to nourish and support it.

Serotonin And Bone Mass Accrual

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The association between 5-HT and osteoporosis was made over a decade ago in patients on SSRIs for depression and continues to be extensively studied with a variety of clinical studies trying to reduce confounding variables . Recent meta-analyses continue to support the association of patients on SSRIs having decreased bone mineral density and increased fracture risk. Even in a pediatric population, treatment with SSRIs is linked to low bone mass .

The effect of SSRIs on blocking bone mineral accrual has been recapitulated in mice treated with SSRIs . Similar to SSRI treatment, deletion of the 5-HT transporter, SERT, also leads to reduced bone mass, indicating that it is SERT inefficacy, rather than off-target drug effects of SSRIs, that accounts for this decrease in bone density . The mechanism of serotonins effect on bone has been actively studied, with effects from brain and gut 5-HT. Interestingly, brain 5-HT is downstream of leptin that is secreted from adipocytes. Receptors in the brain stem respond to leptin to produce 5-HT which in turn decreases sympathetic tone via 5-HT2c . In the Tph2 KO mice, depletion of central 5-HT and increased sympathetic tone leads to decreased bone formation and increased bone resorption . The SSRI-mediated increase of central 5-HT should thus improve bone mass instead of precipitating osteoporosis, suggesting a role for peripheral 5-HT.

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Whats The Difference Between Dopamine And Serotonin

Dopamine and serotonin are both neurotransmitters. This means they are chemical message carriers between nerve cells in the brain as well as to and from other areas of your body. Both are also considered the happy hormones, as they both play a role in positive mood and emotion. Serotonin is associated with happiness, focus and calmness. Dopamine is associated with rewards and motivation. Dopamine and serotonin also share involvement in some mental health conditions, including depression and mood disorders.

Dopamine and serotonin also have some distinct functions. Dopamine controls body movements and coordination. Serotonin helps regulate digestive functions including bowel function and appetite. Dopamine causes a feeling of hunger while serotonin suppresses that feeling. Dopamine is mostly stored in your brain while serotonin is found mostly in your gut.

Sometimes these neurotransmitters work together to stay in a careful chemical balance in your body. Sometimes an imbalance leads to an overproduction of the other neurotransmitter. Having too much or too little of either can cause physical and psychological symptoms.

A note from Cleveland Clinic

Administration Of A Muciniphila And Its Evs Affected The Mrna Expression Of Genes Involved In The Serotonergic System In The Hippocampus Of Mice

To investigate the effects of A. muciniphila and its EVs on the hippocampal serotonergic system, the expression of Tph2, Slc6a4, Mao, Htr1A, Htr2A, Htr5, and Htr6 genes was evaluated. After treatment, an increase in the expression level of the Tph2 gene was observed in both A. muciniphila and EV groups . In comparison with A. muciniphila, EVs induced a higher level of Tph2 gene expression in the hippocampus of mice . The mRNA expression of Slc6a4 and Mao genes significantly decreased in the bacterium and EV groups. Also, EV treatment induced lower levels of Mao expression, compared to the A. muciniphila group .

Figure 4

Administration of A. muciniphila and its EVs induced changes in the expression of hippocampal serotonergic system-related gene in mice. Expression of Tph2 Slc6a4 Mao Htr1A Htr2A Htr5, and Htr6 genes. Data are normalized using RPL13a and -actin as control genes. *, **, ‘P< 0.05 and P< 0. 01 were considered statistically significant, respectively.

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Microbes Help Produce Serotonin In Gut

Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body’s serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis. New research at Caltech, published in the April 9 issue of the journal Cell, shows that certain bacteria in the gut are important for the production of peripheral serotonin.

“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,” explains Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. “We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.”

Peripheral serotonin is produced in the digestive tract by enterochromaffin cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.

Gut Microbes Appear To Influence Serotonin Production By Ec Cells

80-90% Of Your Serotonin Is Produced In Your Gut

For their study, Prof. Hsiao and colleagues wanted to find out which cells the gut microbes might be influencing to have an effect on serotonin levels.

In the first part of the study, they compared peripheral serotonin levels produced from these cells in two groups of mice: one with normal gut microbes and another group of germ-free mice without gut bacteria.

The team found that in the germ-free mice, their EC cells produced around 60% less serotonin than the mice with normal gut bacteria.

And when they restored bacteria colonies in the gut of the germ-free mice, their EC cells began producing normal levels of serotonin showing the effect on the EC cells can be reversed.

In the next part of the study the team set out to find which bacteria in particular were interacting with the EC cells to make serotonin.

They introduced single species and groups of gut microbes one by one into the germ-free mice, and found that serotonin levels went up when there was a certain mix of about 20 species of spore-forming bacteria.

Introducing this particular bacterial mix into the germ-free mice increased the movement of food through their digestive tract. It also changed activity in their blood platelets, which use serotonin to boost clotting.

When the researchers increased these metabolic byproducts in germ-free mice, it increased their levels of peripheral serotonin.

She and her team now plan to find out how their findings may apply to the human brain.

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A Muciniphila Culture And Ev Preparation

The A. muciniphila strain ATCC BAA-835, provided by the DSMZ Institute , was used in this study. The bacterium was routinely grown in a basal mucin-based medium under anaerobic conditions at 37 °C for 37 days. The bacterium was routinely inoculated in brainheart infusion broth , supplemented with 0.5% mucin under anaerobic conditions overnight at 37 °C until an optical density of one was reached.

The bacterial cells were pelleted by centrifugation at 11,000×g for 20 min at 4 °C and washed twice with phosphate-buffered saline . Next, the suspended pellet was immediately placed on ice and used for cell culture treatment and oral administration in mice. We used the remaining supernatant to extract EVs. For this purpose, the supernatant was filtered through a 0.22-mm filter . The extraction of EVs was performed via ultracentrifugation at 200,000×g for two hours at 4 °C, as previously described. The vesicle pellet was resuspended in sterile PBS and stored at 80 °C for further use. The morphology of the isolated EVs was examined, using transmission electron microscopy .

What Is The Effect Of Increased Serotonin On Gastrointestinal Motor And Secretory Functions

Over 50 years ago, it was demonstrated that 5-HT affects intestinal motility in humans, though initial studies suggested it stimulated small bowel motility and inhibited gastric and colonic phasic contractions . Sigmoid colonic motility appears to be increased in patients with IBS. Involvement of 5-HT in the dysmotility observed in IBS remains unclear, although data show a possible relationship between endogenous concentrations of 5-HT and sigmoid colonic motility recorded in both IBS and healthy subjects. There were significant correlations of fed sigmoid colonic motor activity index with platelet-depleted plasma 5-HT concentration in IBS patients and healthy volunteers the R values suggest that the 5-HT level explains less than 20% of the variance in the postprandial colonic motility .

There are, however, other human data suggesting a role of 5-HT mechanisms in colonic motility in disease states and in pharmacological models. First, carcinoid diarrhea is associated with exaggerated colonic tone, particularly postprandially . Second, the 5-HT4 agonist, tegaserod, increases colonic tone and phasic contractility . Third, 5-HT3 antagonists inhibit the increase in colonic tone after a meal in health and in patients with carcinoid diarrhea .

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Balance And Restore Serotonin In The Gut

What causes low serotonin in the gut? Low serotonin in the gut may be caused by poor diet, hormonal changes, and genetics. Chronic stress and lack of sunlight can also cause low levels of serotonin.

Try natural serotonergic therapies to increase your serotonin levels:

  • Improve gut health: Start with a healthy diet. Consume plenty of fiber via fruits and vegetables. Incorporate low-fat meats such as chicken and fish. For carbohydrates, choose whole grain nutrition over refined carbs like white bread and pasta.
  • Include tryptophan-rich foods: Tryptophan is crucial in forming serotonin. Enjoy tryptophan-rich foods like whole milk, beef, lean chicken, turkey, fish, soy, eggs, squash, pumpkin seeds and oats. nuts, tuna, turkey, and oats.
  • Consider a probiotic: Probiotics help balance gut microbiome dysfunction.
  • Manage stress: Identify stressors in your life and consider how to minimize their impact. Often, scheduling time for stress relief activities can help with stress management. Go on a hike, try meditation, or take a cooking class and see if joy and contentment follow.
  • Get outside: 10-30 minutes of sun exposure, several days a week, is a good start. Sunlight triggers the brain to release serotonin.

Another way to restore serotonin levels is through antidepressants called selective serotonin reuptake inhibitors . An SSRI drug inhibits the reabsorption of serotonin by neurons, making more serotonin available for sending messages between neurons.

Why Gut Health Can Boost Serotonin Levels

Microblog: 95% of Serotonin Is in the Gut

We often relate serotonin to our mind because its a feel-good hormone. Mistakenly, wed assume most of our serotonin is made in the pineal or adrenal glands. However, the majority of our serotonin levels come from the gut.

Research suggests 90% of serotonin is formed in our stomach 4. In fact, our stomach bacteria can trigger even more production. That is, as long as the right beneficial bacteria are in the gut biome in the first place.

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Influence Of Gut Microbe

3.1. Synthesis and Functions of Neurotransmitters Modulated by the Gut Microbiota

3.1.1. Glutamate

Table 1.Table 1.

Neurotransmitters Putative Functions in the GutBrain Axis
Glutamate Transfer intestinal sensory signals to the brain through the vagus nerve
GABA Modulate synaptic transmission in the enteric nervous system Modulate intestinal motility and inflammation
Acetylcholine Produced by 33% myenteric neurons in human colon Regulate intestinal motility and secretion and enteric neurotransmission
Dopamine Staphylococcus Affect gastric secretion, motility, and mucosal blood flow Affect gastric tone and motility through nigro-vagal pathway in a Parkinsons disease rat model
Modulate energy intake and thermal homeostasis
Promote gastrointestinal transit and colonic secretion

3.1.2. GABA

3.1.3. Acetylcholine

3.1.4. Dopamine

3.1.5. Serotonin

3.1.6. Trace Amines

3.1.7. Norepinephrine

3.1.8. Modulation of Neurotransmitter Synthesis by Gut Microbiota

3.2. Circulatory Pathway of Gut Neurotransmitter/Precursor Transport and Cognition

3.3. Local Regulation of Neurotransmitters and Impacts on Cognition

3.4. Gut Microbiota and Neurotransmitters in Neurological Disorders

3.4.1. Alzheimers Disease and Parkinsons Disease

3.4.2. Autism Spectrum Disorder and Schizophrenia

3.4.3. Anxiety and Depressive Disorders

Table 2.Table 2.

3.5. Gut Microbiota as a Therapeutic Target for Neurological Disorders

Gut Feelings: How Food Affects Your Mood

The human microbiome, or gut environment, is a community of different bacteria that has co-evolved with humans to be beneficial to both a person and the bacteria. Researchers agree that a persons unique microbiome is created within the first 1,000 days of life, but there are things you can do to alter your gut environment throughout your life.

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Rna Extraction Cdna Synthesis And Quantitative Rt

After 24 h, the total RNA of the treated cells was extracted, using the RNeasy Plus Mini Kit , as previously described. Next, cDNA synthesis was performed, using the PrimeScript RT Reagent Kit , according to the manufacturers instructions. Quantitative RT-PCR assay was also performed, using SYBR Premix Ex Taq II in triplicate. All primer sequences used in this study are shown in Supplementary table.

Gut Microbes Important For Serotonin Production

Do You Have Serotonin Deficiency?

Serotonin is probably best known as a brain chemical that affects emotions and behavior, an imbalance of which is thought to contribute to depression. Less well-known is that scientists estimate 90% of serotonin is made in the gut, and imbalances in this peripheral serotonin have been linked to diseases ranging from irritable bowel syndrome and cardiovascular disease, to osteoporosis.

Now, researchers from the California Institute of Technology in Pasadena report a study in the journal Cell that shows certain bacteria in the gut play an important role in the production of peripheral serotonin.

Senior author Elaine Hsiao, research assistant professor of biology and biological engineering at Caltech, says studies of mice and other lab animals are increasingly showing that changes in gut microbes affect behavior.

She explains that she and her colleagues were interested in finding out more about how gut microbes and the nervous system talk to each other, and:

To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.

In the gut, there are three types of cell we know of that produce serotonin: immune cells, nerve cells or neurons, and enterochromaffin cells.

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