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It takes guts to be mentally ill: Microbiota and psychopathology

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What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.1

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.2

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.3

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.4 The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.5

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