Hey birds! Have you ever had gut feeling or butterflies in your stomach?

Ever had a meeting or exam and felt the need to go to the loo that went longer than expected and it wasn’t caused by anything you ate?  Stomach problems are one of the most common symptoms of stress, depression and anxiety.

These sensations emanating from your belly suggest that your brain and gut are connected.

anxiety depression and gut

Within the first few days of life, humans are colonized by commensal intestinal microbiota. Here, we review recent findings showing that microbiota are important in normal healthy brain function. We also discuss the relation between stress and microbiota, and how alterations in microbiota influence stress-related behaviors. New studies show that bacteria, including commensal, probiotic, and pathogenic bacteria, in the gastrointestinal (GI) tract can activate neural pathways and central nervous system (CNS) signaling systems. Ongoing and future animal and clinical studies aimed at understanding the microbiota–gut–brain axis may provide novel approaches for prevention and treatment of mental illness, including anxiety and depression.

The communication system between your gut and brain is called the gut-brain axis.

Gut and Brain Axis.

How Are the Gut and Brain Connected?Lets see.

These two organs are connected both physically and biochemically in a number of different ways.

The gut-brain axis (GBA) is a bidirectional link between the central nervous system (CNS) and the enteric nervous system (ENS) of the body. It involves direct and indirect pathways between cognitive and emotional centres in the brain with peripheral intestinal functions. The GBA involves complex crosstalk between the endocrine (hypothalamic-pituitary-adrenal axis), immune (cytokine and chemokines) and the autonomic nervous system (ANS).

The GBA primarily combines the sympathetic and parasympathetic arms of the autonomic nervous system (ANS), which drives both afferent and efferent neural signals between the gut and the brain, respectively. The HPA axis meanwhile coordinates adaptive responses against stress including activation of memory and emotional centres in the limbic system of the brain.

The neuro-immuno-endocrine mediators of the GBA allow the brain to influence intestinal function (immune cells, epithelial cells, enteric neurons, and smooth muscle cells). Moreover, the cells of the gastrointestinal (GI) tract are also under the influence of the gut microbiota and recent evidence suggests that there is an emerging concept whereby the microbiome plays an important role in the GBA structure. 


The microbiome refers to all microorganisms in or on their host as well as their genetic material. The microbiota, on the other hand, defines the microbe population in a specific ecosystem, such as those populations found in the gut microbiota or skin microbiota.

Within the gut, there are approximately 1014microorganisms, which is around 10 fold more cells than there are cells in the human body.

Collectively, the genetic material of the microbiome is approximately 150 times greater than the human genome, which has led some scientists to label the microbiome as a ‘superorganism’.

In recognition of this superorganism and the mutualistic co-evolution of humans and microbes, the Human Microbiome Projectwas set up to analyse this unique relationship to determine its role in health and disease.

This is particularly important given the rise in modern antimicrobial treatments, disinfectant use and harsh cleaning products that are frequently marketed and sold as necessary for good human health.

Within the gut, the bacterial phyla Firmicutes and Bacteroidetes are approximately 75% of the gut microbiota and both of these phyla are very sensitive to change

Disruptions to the microbiome are increasingly becoming associated with the prevalence of anxiety , depression and neuropsychiatric disorders that affect today’s society.

The Vagus Nerve and the Nervous System

Neurons are cells found in your brain and central nervous system that tell your body how to behave. There are approximately 100 billion neurons in the human brain.

Interestingly, your gut contains 500 million neurons, which are connected to your brain through nerves in your nervous system .

The vagus nerve is one of the biggest nerves connecting your gut and brain. It sends signals in both directions.

For example, in animal studies, stress inhibits the signals sent through the vagus nerve and also causes gastrointestinal problems .

Similarly, one study in humans found that people with irritable bowel syndrome (IBS) or Crohn’s disease had reduced vagal tone, indicating a reduced function of the vagus nerve.

An interesting study in mice found that feeding them a probiotic reduced the amount of stress hormone in their blood. However, when their vagus nerve was cut, the probiotic had no effect.

This suggests that the vagus nerve is important in the gut-brain axis and its role in stress.


Your gut and brain are also connected through chemicals called neurotransmitters.

Neurotransmitters produced in the brain control feelings and emotions.

For example, the neurotransmitter serotonin contributes to feelings of happiness and also helps control your body clock.

Interestingly, many of these neurotransmitters are also produced by your gut cells and the trillions of microbes living there. A large proportion of serotonin is produced in the gut.

Your gut microbes also produce a neurotransmitter called gamma-aminobutyric acid (GABA), which helps control feelings of fear and anxiety .

Studies in laboratory mice have shown that certain probiotics can increase the production of GABA and reduce anxiety and depression-like behavior.

Gut Microbes Make Other Chemicals That Affect the Brain

The trillions of microbes that live in your gut also make other chemicals that affect how your brain works.

Your gut microbes produce lots of short chain fatty-acids (SCFA) such as butyrate, propionate and acetate.

They make SCFA by digesting fiber. SCFA affect brain function in a number of ways, such as reducing appetite.

One study found that consuming propionate can reduce food intake and reduce the activity in the brain related to reward from high-energy food.

Another SCFA, butyrate, and the microbes that produce it are also important for forming the barrier between the brain and the blood, which is called the blood-brain barrier.

Gut microbes also metabolize bile acids and amino acids to produce other chemicals that affect the brain.

Bile acids are chemicals made by the liver that are normally involved in absorbing dietary fats. However, they may also affect the brain.

Two studies in mice found that stress and social disorders reduce the production of bile acids by gut bacteria and alter the genes involved in their production.

Gut Microbes Affect Inflammation

Your gut-brain axis is also connected through the immune system.

Gut and gut microbes play an important role in your immune system and inflammation by controlling what is passed into the body and what is excreted.

If your immune system is switched on for too long, it can lead to inflammation, which is associated with a number of brain disorders like depression and Alzheimer’s disease.

Lipopolysaccharide (LPS) is an inflammatory toxin made by certain bacteria. It can cause inflammation if too much of it passes from the gut into the blood.

This can happen when the gut barrier becomes leaky, which allows bacteria and LPS to cross over into the blood.

Inflammation and high LPS in the blood have been associated with a number of brain disorders including severe depression, dementia and schizophrenia .


Much of the research into intestinal microbial composition has been carried out using animal models, either by adding pathogenic bacteria and monitoring behaviour or by inducing depression-like symptoms and rescuing these animals through treatment.

In a study by Desbonnet and colleagues, they showed that rats that had undergone maternal separation (model of induced depression-like behaviour) could be rescued by treatment with the probiotic Bifidobacterium infantis in conjunction with 30-mg/kg citalopram.

Maternal separation causes reduced mobility, increased peripheral proinflammatory interleukin (IL)-6 secretion, and reduced levels of norepinephrine in these rats.

However, these symptoms were reversed after treatment with both the probiotic and citalopram but not when they were administered separately.

Functional MRI analysis has previously shown there is a chronic low-level inflammatory condition in many cases of depression.

In these cases, depression is reliably associated with inflammatory biomarkers such as tumour necrosis factor (TNF)-α, IL-6, and C-reactive protein.

There are several lines of evidence that suggest that the presence of these inflammatory markers is suggestive of gut permeability issues and the presence of inflammatory inducers such as LPS.


Autism-spectrum disorder (ASD) is a group of neurodevelopmental disorders that are characterised by deficits in social interactions including verbal and nonverbal behaviours.

Researchers believe that these ASD-like behaviours are a result of a complex interplay between genetic defects and environmental risk factors causing abnormal neurodevelopment during maturation in utero and in early childhood.

Analysis of genetic material in faecal matter from children with ASD showed a correlation between bacteria such as Clostridium and Desulfovibrio and altered neuro-behavioural development as observed in ASD.

Anecdotally, there have been observations of improved symptoms in ASD children who experience changes in gut microflora populations caused by ingestion of either antibiotics against these bacteria or probiotics that provide the gut with more synergistic bacteria.

Furthermore, analysis of faecal samples from ASD children has shown an imbalance in certain microbiota species with overall less diverse gut microbiota species.

It was reported that these compositional differences included a lower abundance of Prevotella and Coprococcusspecies. The differences in microbial diversity and composition will result in changes in many neuroactive microbial metabolites.

Therefore, GI dysbiosis is a possible factor in ASD etiopathogenesis just as it has been suggested to be a causative factor in psychiatric disorders such as depression.

The differences in microbial diversity and composition results in changes in many neuroactive microbial metabolites. Therefore, GI dysbiosis is a possible factor in ASD etiopathogenesis.


Many of the studies on gut microbiota and schizophrenia have been preclinical studies and carried out in a schizophrenia-like behaviour rat model.

Experiments show that treatment with the human commensal bacteria, Bacteroides fragilis can improve microbiota composition, correct gut permeability, and improve anxiety-like symptoms in this model.

Furthermore, clinical studies on subjects with schizophrenia showed the presence of increased levels of lactic acid bacteria in the gut lumen, including Lactobacillus casei, and Lactobacillus lactis as well as Streptococci species such as Streptococcus mutans and Streptococcus thermophilius.

The increased presence of these bacteria species is associated with alterations in adaptive Th2 immune responses which is known to be present in schizophrenia.

Administration of probiotics to these individuals altered the microbiome and appeared to normalise some behavioural symptoms.

In addition, the pathogenic bacteria Clostridium is known to produce 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) and p-cresol, which are microbial metabolites that can inhibit an enzyme called dopamine beta-hydroxylase.

This enzyme converts dopamine to norepinephrine causing a concurrent rise in dopamine levels in the brain.

This can lead to behavioural problems and has been associated with exacerbating psychotic episodes in schizophrenia.

2019 paper compared the gut microbial communities of patients with schizophrenia and healthy controls to evaluate whether microbial dysbiosis was linked with episodes of illness or the severity of  symptoms. The study showed the following findings:

  • Microbial compositions of patients with schizophrenia were characterised by lower within-sample diversity.
  • Bacterial taxonomic families Veillonellaceae, Prevotellaceae, Bacteroidaceae, and Coriobacteriaceae were increased in patients with schizophrenia.
  • Lachnospiraceae, Ruminococcaceae, Norank, and Enterobacteriaceae were decreased in patients with schizophrenia.
  • Altered gut microbial composition observed in SCZ is specific relative to the gut microbiome changes we observed in depression.
  • Veillonellaceae was negatively correlated with PANSS, whereas Bacteroidaceae, Streptococcaceae, Lachnospiraceae were positively correlated with PANSS.
  • The combination of Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae can distinguish patients with schizophrenia from healthy controls. This combination of gut microbiota may have potential diagnostic value in schizophrenia.
  • The researchers also carried out fecal microbiota transplantation (FMT) experiments in mice and found that mice transplanted with schizophrenia microbiota displayed locomotor hyperactivity, decreased anxiety and depressive-like behaviors, and increased startle responses, suggesting that the disturbed microbial composition of schizophrenia microbiota recipient mice was associated with several endophenotypes characteristic of mouse models of schizophrenia.


Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterised by altered bowel habits in association with abdominal discomfort or pain in the absence of detectable structural and biochemical abnormalities.

Psychiatric co-morbidity e.g depression and anxiety are overrepresented in individuals with IBS.

Besides altered gastrointestinal motility, visceral hypersensitivity, post-infectious reactivity, alteration in faecal microflora, bacterial overgrowth, food sensitivity, carbohydrate malabsorption, and intestinal inflammation, the gut brain alteration is known to be a major factor in the pathogenesis of IBS.

Modulation of the gut-brain axis in IBS offers a promising therapeutic target for the future.

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