The Gut?Brain Relationship

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InnoVision Professional Media has chosen a very timely topic of vital importance for its first medical and scientific conference: the interchanging relationship between the gut microbiome and the brain.

The Gut?Brain Relationship Conference will expose the evidence that the microbiome has an even greater influence on the brain than initially assumed: It is involved in a number of ways in the proper functioning of the brain. The opposite is also true: Abnormalities of the microbiome can cause abnormalities in the brain and in behavior of the host. Brain-related problems are a huge burden for society.

The Human Genome Project revealed that the human gene pool consists of 26 000 units; in comparison, rice has 46 000 functioning genes, and the microbiome has 4 million distinct bacterial genes, 95% of them located in the large intestine. It is this microbiota that directs our immune system, modifies our epigenome, and regulates our metabolism. The majority of chemicals circulating in our blood are synthesized by the microbiome, and they have a profound effect on our neuroendocrine response and behavior. The central nervous system is affected by immunologic, neuroendocrine, and biochemical processes.

Researching the gut microbiota has brought us a new understanding in noncommunicable diseases, such as cardiovascular disease and type 2 diabetes. The intestinal microbiome begins at birth and is influenced early on by delivery method and feeding mode, reaching an adult-like state at approximately age 3 years. Early life is critical to the development of the gut microbiome and gut?brain signaling pathways. Disturbances due to stress, severe illness, repeated treatments with antibiotics, chemicals in food and liquids, and others can affect the microbiome and the hypothalamic?pituitary?adrenal (HPA) axis.

Components of microbial cell walls constantly and relentlessly stimulate the immune system, keeping it in a state of activation. As an example, the microbiome interacts with the HPA axis to regulate sleep. Bacterial peptides stimulate the production of interleukin 1? (IL-1?) and tumor necrosis factor ? (TNF-?) from macrophages. Lipopolysaccharides (LPS) from the cell wall of gram-negative bacteria induce the production of IL-18. Approximately 1 g of LPS is in the adult gut. IL-18, IL-1?, and TNF-? induce nonrapid eye movement sleep, and cortisol inhibits their synthesis. At approximately midnight, IL-1? and TNF-? peak, which is when cortisol is at its lowest levels, and they are at their lowest levels in the early morning hours when cortisol rises. Disrupted sleep occurs with excessive cytokine levels. LPS increases plasma concentrations of proinflammatory IL-6 and TNF-?, as well as the anti-inflammatory IL-10 and IL-1 receptor antagonist, and cortisol and norepinephrine levels. This translates into anxiety and depressed mood, impaired long-term memory, and increased sensitivity to visceral pain.

The above balance between immune activation and inflammation can be disrupted by a myriad of factors, and alterations in the diversity, stability, and composition of the gut microbiota due to antibiotics; environmental toxins; the Western diet, rich in carbohydrates and saturated fats; stress; alcohol consumption; geography; exercise; and aging have been linked to a number of disorders, including autoimmune, gastrointestinal, metabolic, as well as brain disorders. The result is increased intestinal permeability, usually referred to as ?leaky gut,? when inflammation brings about changes in the mucosal gut barrier that allows harmful molecules to enter the blood stream. This, in turn, elicits an inflammatory response in the body and affects the blood?brain barrier, making it ?leaky.?

This bidirectional gut and brain communication is controlled by the central and enteric nervous systems, and it is affected by the endocrine and immunoinflammatory systems and neurotransmitters, especially tryptophan and serotonin.

Disturbances of the gut microbiota have been linked to multiple sclerosis, Parkinson?s disease, autism spectrum disorder, and others. Western diet is in general proinflammatory, and inflammation is where the problems arise. Several studies have shown that alterations of the gut microbiome that alter the delicate balance of tryptophan metabolism and serotonergic signaling affect both the central and enteric nervous systems and can bring about abnormalities such as anxiety, depression, visceral pain, abnormal sexual behavior, mood alterations, poor memory function, loss of cognitive flexibility, and others as mentioned above.

This conference on the gut?brain relationship, with an excellent line-up of speakers, will help us all gain a better understanding of this emerging and fascinating subject.

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