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Gut-Brain Axis

The term ‘gut-brain axis’ refers to a complex bidirectional communication system between the gastrointestinal tract and the central nervous system (CNS). The gut and brain constantly communicate and influence each other through neural, endocrine, and immune signals in an interaction referred to as the gut-brain axis. 

Gut-Brain Axis


This system ensures the proper maintenance of gastrointestinal homeostasis and probably affects higher cognitive functions, such as effect and motivation. Within this communication system, the gastrointestinal tract, including the gut microbiota, sends information on energy status to the brain, which transmits feedback to the gastrointestinal tract after integrating these and other inputs. It allows regulating food intake and other physiological processes occurring in the gastrointestinal tract, including motility, secretion, digestion, and absorption, which helps maintain energy homeostasis. 

The brain has a direct impact on the stomach and intestines. For example, the thought of eating can release the stomach’s juices before the food goes there. This association goes both ways. A disturbed intestine can send signals to the brain, just as a disturbed brain can send signals to the gut. 

Therefore, a person’s stomach or intestinal upset can be the cause or the product of anxiety, stress, or depression. That is because the brain and the gastrointestinal (GI) system are intimately connected.

This is especially true in cases where a person experiences gastrointestinal upset for no apparent physical reason. For such active GI disorders, it is challenging to try to heal a distressed gut without considering the role of stress and emotion.

How does the gut-brain axis work?

These two organs, Guts, and Brains, are connected both physically and biochemically in many different ways. This bidirectional communication GBA network includes the central nervous system (CNS), both the brain and spinal cord, the autonomic nervous system (ANS), the enteric nervous system (ENS), and the hypothalamic-pituitary-adrenal (HPA) axis. 

The Gut-Brain Axis involves complex crosstalk with the brain sending messages to the gut and vice versa.

1. The Vagus Nerve – The Vagus nerve connects the gastrointestinal tract to the brain. The Vagus nerve links the gastrointestinal tract, heart and lungs to the brain. Vagal sensory neurons and afferent Spinal cells carry feedback from the intestinal end to the brain stem, engaging the hypothalamus (a brain region that controls hunger and emotions) and the limbic system (responsible for regulating emotions). Likewise, descending projections from the limbic system (activated via stress) influence the autonomic activity of the gut.

Vagus Nerve

2. Neuroendocrine (gut hormone) signalling – Bacterial products are known to stimulate enteroendocrine cells (EECs), a gut hormone to produce several neuropeptides such as peptide YY, neuropeptide Y (NPY), cholecystokinin, glucagon-like peptide-1 and -2, and substance P. (Neuropeptides are the most diverse class of signaling molecules in the brain engaged in many physiological functions). These neuropeptides then enter the bloodstream and directly influence the enteric nervous system. 

Neuroendocrine (gut hormone) signalling

3. Interference with Tryptophan metabolism – Approximately 95 of serotonin (5-HT) is produced by gut mucosal enterochromaffin cells. Peripherally, 5-HT is involved in regulating GI secretion, motility (smooth muscle contraction and relaxation), and pain perception. In contrast, the brain is involved in regulating 5-HT mode and cognition. The gut microbiota also plays an important role in tryptophan metabolism, a precursor to serotonin production.

 Interference with Tryptophan metabolism

4. The Immune System – The gut-associated lymphoid tissue comprises 70% of the body’s immune system and can be conceptualized as the largest immune organ in the body. 

Immune System

5. Altered Intestinal Permeability – Chronic stress has been shown to alter intestinal permeability (leaky gut syndrome), associated with a low-grade inflammation that can be functionally linked to psychiatric disorders such as depression. 

In many of these cases, it is the presence of an increase in the circulation of bacterial endotoxins, called lipopolysaccharides (LPS), is the primary risk factor for the disease. Alternatively, other studies have suggested that gut microbiota may produce neuroactive substances that may affect the underlying symptoms of neuropsychiatric disorders. This alternative hypothesis may point to the important and relevant role of gut microbiota in the pathophysiology of many diseases, including schizophrenia, autism, anxiety, and depression.

Altered Intestinal Permeability

6. Production of Microbial Metabolites – Many Lactobacillus species and Bifidobacterium produce gamma-aminobutyric acid (GABA), the brain’s primary inhibitory Neurotransmitter. In addition, Candida, Escherichia, and Enterococcus produce the neurotransmitter serotonin, while some Bacillus species have been shown to produce dopamine. Bacteria also produce short-chain fatty acids (SCFAs), such as butyric acid, propionic acid, and acetic acid, that can stimulate the sympathetic nervous system, mucosal serotonin release and thus influence the memory and learning process in the brain. 

Production of Microbial Metabolites

How does the Gut-Brain Axis affect the body?

There is a strong relationship between mental health problems and gastrointestinal symptoms such as heartburn, acid reflux, indigestion, bloating, pain, constipation, and diarrhea.

Depression and anxiety can cause changes in the gut microbiome. Animal research has shown that changes in the gut microbiome and inflammation in the gut affect the brain and lead to Parkinson’s disease, autism, anxiety, and depression.

  • Stress hinders the signals sent through the Vagus nerve and also causes gastrointestinal problems.
  • One study (PubMed Central: Highly respected database from the National Institutes of Health) in humans found that the reduced vagal tone, indicating a reduced function of the Vagus nerve, causes irritable bowel syndrome (IBS) or Crohn’s disease in people.
  • The alteration in Neurotransmitter (a chemical that links the gut to the brain, control emotion and feelings.) causes fear, anxiety, and depression.
  • Gut microbes generate lots of short-chain fatty acids by digesting fiber that affects brain function in many ways, such as reducing appetite. Some are also important for forming the barrier between the brain and the blood, called the blood-brain barrier.
  • Gut microbes also metabolize bile acids (involve to absorb dietary fats) and amino acids to produce other chemicals that affect the brain.
  • Two studies (PubMed Central: Highly respected database from the National Institutes of Health) in mice have shown that stress and social disorders reduce the production of bile acids by gut bacteria and alter the genes involved in their production.
  • The gut is also connected to the brain through the immune system. If the immune system is shut down for too long, it can cause the inflammation associated with many brain diseases such as depression and Alzheimer’s disease.
  • Lipopolysaccharide (LPS) is an inflammatory toxin made by certain bacteria. It can cause inflammation if most of it passes from the gut into the blood. It can happen when the gut barrier becomes leaky, allowing bacteria and LPS to enter the bloodstream.
  • Inflammation and high LPS in the blood are associated with many brain disorders, including severe depression, dementia, and schizophrenia.

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