The term "microbiome" refers to every microorganism in or on its host and its genetic makeup. Contrarily, the microbiota describes the bacterial populations found in a particular ecosystem, such as those in the gut microbiota or the skin microbiota. 

There are around 10 times as many cells in the intestine as there are in the human body. Some scientists have referred to the microbiome as a "superorganism" since it contains genetic material about 150 times larger than the human genome. 

About 75% of the gut microbiota is made up of the bacterial phyla Firmicutes and Bacteroidetes, both of which are highly sensitive to change. The incidence of allergies, autoimmune diseases, metabolic problems, and neuropsychiatric disorders that plague today's society is increasingly linked to microbiome disruptions. 

There are seven major parts in the stomach and brain connection cycle. Each area utilises the microbes of gut microbiota, which then interact with the GBA. Here's a brief overview of how they react to the GBA and their purpose.  

1. The Vagus Nerve 

• The brain stem receives feedback from the intestine end via spinal and vagal: emery neurons, which then activate the limbic and hypothalamus system (responsible for the regulation of emotions) 
• The limbic system's descending projections, which are stimulated by stress, impact the gut's autonomic activity. 

2. Neuroendocrine (gut hormone) signalling 

• Bacterial products induce enteroendocrine cells (EECs) to produce several neuropeptides, including substance P, peptide YY, and neuropeptide Y (NPY). 
• These neuropeptides subsequently affect the enteric nervous system after they enter the bloodstream. 

3. Interference with tryptophan metabolism 

• Gut mucosal enterochromaffin cells produce 95% of the serotonin (5-HT) in the body. 
• In the body, 5-HT controls motility (smooth muscle contraction and relaxation), GI secretion and pain perception; in the brain, 5-HT is thought to control mood and cognition. 

• Additionally, the gut microbiota is crucial for the metabolism of tryptophan, which is a precursor to serotonin. 

4. The immune system 

• The largest immunological organ in the body, the gut-associated lymphoid tissue, or GALT, makes up 70% of the body's immune system.  

5. Altered intestinal permeability 

• Leaky gut syndrome, which is connected to low-grade inflammation and has been functionally linked to psychiatric diseases, including depression, has been demonstrated to be altered by chronic stress. 

• Lipopolysaccharides (LPS), bacterial endotoxins that circulate in the blood, significantly contribute to illness risk in many of these situations. 
• Alternately, some research has indicated that the gut microbiome can create neuroactive chemicals that could affect the primary symptoms of neuropsychiatric diseases. 
• This alternate theory might indicate that the gut microbiota plays a significant and pertinent role in the pathophysiology of various diseases, such as schizophrenia, autism, anxiety, and depression. 

6. Production of microbial metabolites

• Numerous species of Bifidobacterium and lactobacillus produce gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. 

• Additionally, some bacillus species have been demonstrated to create dopamine, whereas candida, Escherichia, and enterococcus produce serotonin. 
• Short-chain fatty acids (SCFAs), such as butyric acid, propionic acid, and acetic acid, are also produced by bacteria. These SCFAs can stimulate the sympathetic nervous system and mucosal serotonin production, which can have an impact on memory and learning. 

7. HPA Axis involvement 

Although chronic stress may result in a clinically significant imbalance in the microbial community, acute stress has no impact on the gut microbiota. 

• A leaky gut resulting from increased gut permeability brought on by elevated cortisol levels subsequently promotes a systemic inflammatory response. 
• The pro-inflammatory state caused by a leaky gut is demonstrated by elevated levels of TNF-, interferon-, and IL-6 in the blood. 
• The HPA axis is known to be activated by IL-6, which also gradually downregulates glucocorticoid receptors. These receptors provide a feedback mechanism that inhibits the HPA axis, but when downregulated, the HPA axis becomes overactive and sensitive.