Introduction
The ratio between the microorganisms living in the human body and human cells is 1:1, where the vast majority of it resides in the colon representing the largest reservoir for microorganisms. Microbiota - gut-liver-brain axis regulates the occurrences and development of many diseases. Much research has been conducted on this that has helped understand the pathogenesis of the conditions. The gut microbiota combines with the enteric nervous system (the nervous system which controls the blood flow, mucosal transport, and secretions and aids in immune system functions), autonomic nervous system (it controls physiological processes such as heart rate, respiration, digestion, blood pressure, and sexual arousal), neuroendocrine (the control of hormones by the brain) and neuroimmune system (the interactions between the brain and the immune system) and forming the microbiota-gut-brain axis. The signaling pathway of the gut-liver-brain axis occurs through various mechanisms, but still, these areas need to be explored.
Studies made in recent years have shown an association between gut microbiota and many diseases, such as anxiety, depression, obesity, diabetes, Parkinson's disease, and Alzheimer's disease. This relationship is an important area and should be studied since it will help develop personalized healthcare strategies in the coming years so that people can directly adjust their gut microbiota to cure some diseases.
Any disturbance caused in the gut microbiota can lead to the onset of diseases. Thus, it is essential to understand the influencing factors causing the disturbance to potentially target and prescribe personalized medications for some disorders in the future.
What Is the Microbiota-Gut-Brain Axis?
The gut-brain axis is a two-way interaction between the central nervous system and is done in two ways.
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Up-Down: The gastrointestinal tract influences the brain and the emotional state to impact gastrointestinal homeostasis (a condition for optimal functioning).
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Down-Up: The gut microbiota influencing brain function and behavior.
Up-Down Regulation:
The brain interacts with the gastrointestinal tract in three primary levels, which include:
1. Enteric Nervous System: This system senses and response to the gut microbiota by converting chemical signals from the environment into nerve impulses that spread to the entire intestine and other body organs, including the central nervous system.
2. Autonomic Nervous System: This system controls the main functions of the gastrointestinal tract, which include:
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Gastrointestinal motility.
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Regulation of gastrointestinal blood flow.
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Secretion of enzymes and acids for digestion.
Recent studies have confirmed that the autonomous nervous system affects the stem cell (cells that can renew and differentiate on their own) proliferation of the intestine.
3. Central Nervous System: This system influences the gastrointestinal tract by regulating sympathetic (responsible for intense physical activity) and parasympathetic nerves (responsible for rest) and some structures involved in this process, including the amygdala, hypothalamus, nucleus tractus solitarius, etc.
Down Up-Regulation:
The intestine cells produce various signal molecules that can effectively cross the blood-brain barrier to the central nervous system passing via the bloodstream. For example, a food high in salt induces T helper cell 17 in the intestine, which increases circulating plasma interleukin 17, which acts on endothelial cells (cells found in the inner lining of blood vessels) of the brain that can inhibit the production of nitric oxide by endothelial cells resulting in cerebral perfusion (a measure of oxygen delivery to cerebral tissues) reduction and cognitive dysfunction. Most of the microbiota's neurotransmitters, including serotonin, dopamine, and aminobutyric acid, cannot pass through the blood-brain barrier that protects the brain. Instead, these neurotransmitters can directly act on specific receptors of primary afferent neuron cell bodies or cross the blood-brain barrier through the precursors and be converted into active neurotransmitters. A classic example would be when the gut microbiota affects the metabolism of serotonin precursor tryptophan. This will, in turn, affect the serotonin signal in the central nervous system since tryptophan concentrations in the plasma correlate with serotonin levels in the brain.
What Evidence Proves the Role of Gut Microbiota in the Gut-Brain Axis?
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Studies on animals have shown that the brain is affected without a microbiome. One example is mice grown in a sterile environment have more exaggerated physiological responses to stress.
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Transplanting gut microbiota can change the pathophysiology of the brain. An example of this is the intestinal microorganisms of patients with Parkinson's disease were isolated and transplanted into the intestinal tract of a mouse model with the condition, aggravating their pathological changes.
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Some research showed the elimination of stress, depression, and anxiety-like behaviors in preclinical models and human studies using probiotics.
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Bacterial colonization of the gut plays a significant role in the development and maturation of essential systems, including the immune and endocrine systems that propagate programming and signaling in the central nervous system after birth.
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An oral antibiotic, namely Rifaximin, can treat hepatic encephalopathy (the loss of brain function when a damaged liver does not remove the toxins from the blood) that modulates gut microbiota and its end products.
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Specific regions of the brain are affected by the gut microbiota and its metabolites. Labus et al. demonstrated that the composition and function of gut microbiota in inflammatory bowel syndrome are related to changes in particular brain areas. It was also observed that the microbial composition correlated with the structural measurements of specific brain regions. Thus, it should be noted that doctors must pay attention to the role of gut microbiota and gut-brain axis to analyze the disease's mechanism and develop a proper treatment plan in the future.
What Is the Microbiota-Gut-Liver-Brain Axis?
The gut and liver relationship has been observed more in recent years due to a gradual increase in the occurrence of liver diseases. The gut and liver communicate through the portal vein, biliary tract, and systemic circulation. Microbial metabolites and microbial-associated molecular patterns (MAMPs) are transported to the liver via the portal vein, thus impacting liver function. On the other hand, the liver transports bile salts and antimicrobial molecules to the intestinal lumen via the biliary tract to maintain gut eubiosis (microbiota in a disease-free host) by controlling unrestricted bacterial overgrowth. Thus, disturbances in the eubiosis of the gut will reduce the activation of nuclear bile acid receptors Farnesoid X receptor (FXR) and Takeda G-protein coupled Receptor (TGR), which leads to a decrease in the synthesis of secondary bile acids. This mechanism contributes to bile salt retention and bacterial overgrowth leading to liver disease. Thus, the liver cannot function properly.
Conclusion
Thus, when a disease occurs, it is not only important to pay attention to the role of the gut-brain axis in the disease, but also the role of the liver in the gut-brain axis should be equally considered, especially in liver diseases such as hepatic encephalopathy, which is a classic example of the microbiota-gut-liver-brain axis disease model.
