COMMENTARY

The Microbiome and Brain Health: What's the Connection?

Sarah R. Dash

Disclosures

March 24, 2015

In This Article

The Biome and Brain Disorders

Microbial and neurologic development share similar windows of developmental vulnerability, during which they are particularly susceptible to damage.[6] The mother provides an infant's first bacterial exposure; thus, maternal health is very important to a how a child's microbiome develops.[7] Maternal illness and use of medications may disrupt an optimal microbiota transfer to the infant.

Early life continues to be developmentally critical; disruptions, such as stress or severe illness, can be damaging to gut/brain signaling and have been linked to brain disorders later in life.[6] Several animal studies have shown that early life stress can alter the development of the key stress response system, the hypothalamic-pituitary-adrenal axis, establishing a lifelong alteration in how an animal responds to stress.[8,9] The impact on the two-way relationship between stress and the gut microbiota may be at the root of this problem. Maternal stress and infection during pregnancy have been linked to neurologic and central nervous system disorders, such as schizophrenia, autism spectrum disorders, and distinct cognitive and behavioral symptoms later in life, and these outcomes may be mediated by the bacteria living in the gut.[10,11]

Microbiota and Neurologic Disease

Gut disturbances—both gastrointestinal discomfort and altered microbiota —have been linked to neurologic disorders, including multiple sclerosis (MS), autism spectrum disorders, and Parkinson disease. Environmental risk factors for neurologic disease often promote the immunoinflammatory response.

There is suggestion that the misfolding of proteins in the brain may be an etiologic explanation for some neurologic disorders. Brain inflammation, which may originate from the gut, is one notable hypothesis behind protein misfolding.[12,13]

The proinflammatory state prompted by gut dysbiosis has also been linked to various autoimmune disorders, again including MS.[14] MS is most common in Western countries,[15] where dietary patterns thought to promote a proinflammatory profile and disrupt optimal gut microbiota states are common.[16] Of note, lipopolysaccharides and antibodies against various antigens have been observed in patients with MS and Parkinson disease, with both markers signaling an increase in intestinal permeability.[17,18]

Relatedly, neurodegenerative diseases, such as Alzheimer disease and generalized cognitive decline, are marked by age-related brain changes, along with disturbed immune function and increased oxidative stress[19]; these factors have been shown in animals to be influenced by diet and the gut microbiota.[20] Brain-derived neurotrophic factor, a neurotrophin that protects and encourages survival of healthy brain cells and whose production may be influenced by gut bacteria, is shown to be decreased in people with Alzheimer disease.[21] It appears that age-related changes in the gut microbiota might be bidirectionally linked to age-related neurodegeneration.[22]

It is notable that the unhealthy dietary patterns that negatively influence the gut microbiome are also risk factors for depression in older adults,[23] whereas healthier diets protect against cognitive decline.[24]

The Microbiota and Psychiatric Disorders

The notion of the gut/mental health connection has recently started to gain traction. It is now thought that various psychological disorders, depression in particular, may be inflammatory disorders, and that the gut may be an important mediator of these conditions.[25,26] In numerous animal studies, microbial manipulation produced behaviors related to anxiety or depression,[27,28] and one study demonstrated that the anxious phenotype could be transferred via the intestinal microbiota between animals.[29]

The coping mechanisms for dealing with psychological stress appear to be programmed in early life, so this development may set us up to deal with stress throughout our lives—with some coping mechanisms working better than others.[30] Given the amount of serotonin in the gut and the influence of the gut microbiota on serotonin's precursor, tryptophan, examining its role in mental health is worthwhile. Early correlational evidence has linked functional and structural damage in the gut with depression,[25] schizophrenia,[31] and autism.[32]

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