Microbiome-gut-brain axis plays role in evaluating, treating psychiatric illness

David Scheiderer

ORLANDO, Fla. — Strategies shown to decrease intestinal and blood-brain barrier permeability — like probiotics, prebiotics and supplements such as fish oil — may help subgroups of patients with depression and other psychiatric disorders, according to a presenter here.

The connection between blood-brain barrier permeability, also known as “leaky brain,” and intestinal permeability, or “leaky gut,” may play a role in evaluating and treating psychiatric disorders, David Scheiderer, MD, MBA, DFAPA, director of education at Integrative Psychiatry Inc, said during his presentation.

‘All disease begins in the gut’

An emerging field of research indicates that the microbiome-gut-brain axis is relevant to mood and behavior. In his presentation, Scheiderer discussed how to use prebiotics, probiotics, antibiotics and dietary changes to affect gut microbiota, and advised when to include gut strategies in the evaluation and treatment of psychiatric disorders.

“For the purposes of this discussion, the concise and pithy theme is ‘all disease begins in the gut,’” Scheiderer said. “Chronic, degenerative diseases of civilization, including most mental disorders, are on the rise.”

Chronic degenerative conditions have overtaken infections as a main source of illness and death, partially due to environmental changes that have increased disease liability of genetic profiles. This transition is linked to low-grade chronic systemic inflammation, also known as metaflammation, explained Scheiderer. Evidence has shown that the primary cause of inflammation may be “gut-brain axis” dysfunction. This system-wide inflammation causes problems in psycho-neuro-immunological parameters like neurotransmitters and hormones.

“Here’s the wheel of inflammatory ‘misfortune:’ Decreased gut microbial diversity dysbiosis leads to increased intestinal permeability, which then causes [lipopolysaccharide] translocation, which then gives rise to increases in cytokine oxidative and nitrosative stress, which leads to increased blood-brain barrier ‘leakiness,’” Scheiderer explained. “If your gut ‘leaks,’ likely so does your blood-brain barrier. That’s how inflammation goes from body to brain and conversely from brain to body.”

Dysbiosis, defined as microbial imbalance or maladaptation in the body, such as an impaired microbiota, can be caused by infection, antibiotics and lifestyle choices. Antibiotics, proton pump inhibitors, c-section birth, and chronic use of some antidepressants all can affect the gut microbiome. Drug abuse also impacts blood-brain-barrier dysfunction, he said. The spike in autism diagnoses are associated with gut microbiome changes, according to Scheiderer, and there are links between ADHD and the gut microbiome, as well as Alzheimer’s disease and gut microbiome.

“‘Leaky gut’-induced inflammation will eventually lead to ‘leaky brain,’ which is increased permeability of the blood-brain barrier,” he said.

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Clinical implications

“We are not better today at treating depression than we were 70 years ago,” Scheiderer said. “One of the reasons is that everybody who presents with depression gets the same ‘one size fits all’ serotonin-dominant reuptake inhibitor.”

Prior study found that subtypes of major depression disorder were stable across a 2-year follow-up and had distinct determinants; these findings suggest that identified subtypes are clinically significant, according to the presentation. Profiling depressive symptom patterns may offer a useful way to begin developing individualized intervention and treatment programs.

Atypical depression is linked to obesity, diabetes, metabolic syndromes, history of trauma and early adversity, according to Scheiderer.

“When you see atypical depression, I want you to think inflammation,” he said.

In a study examining the 2-year course of depressive disorders in patients with subtypes of MDD using antidepressants, researchers found that inflammatory and metabolic dysregulations predicted a more chronic course of depressive disorders, indicating that inflammatory and metabolic abnormalities may worsen depression course due to lower antidepressant treatment response. There may be a need for alternative intervention treatments for these patients, Scheiderer said.

“In other words, don’t just keep doing the same thing if you’re depressed and inflamed; come up with different strategies,” he said.

Another study assessing an inflammatory biomarker as a differential predictor of depression outcome in patients treated with escitalopram and nortriptyline found that an easily accessible peripheral blood biomarker — C-reactive protein (CRP) — may contribute to improved outcomes in MDD when they receive personalized treatment. Other evidence supports IL-17 as a possible predictor of better outcomes in some patients with depression treated with bupropion-SSRI combination.

An anti-inflammatory diet —which includes vegetables, whole grains, fruits, lean protein, fish oil, green tea — should be considered to improve inflammation, according to the presentation. Probiotics, reducing sugar, prebiotics/fiber, and maintaining glutamine stores in the body also support the gut barrier.

To “tidy up blood-brain barrier leakiness” Scheiderer discussed using Nrf2 pathway activators (eg, curcumin, green tea, garlic, cinnamon). Some recent evidence also supports probiotics and prebiotics to possibly slow down the progression of Alzheimer’s disease. In addition, probiotic supplementation was associated with lower short-term rehospitalization rates in bipolar disorder in previous research.

To conclude, Scheiderer summarized that clinicians should:

obtain a peripheral blood marker of inflammation;
use or add medication that increases dopamine and norepinephrine;
consider not using SSRI treatments for depressed patients with inflammation; and
employ anti-inflammatory lifestyle modifications. – by Savannah Demko

Reference:

Scheiderer DJ. Leaky gut, leaky brain: The emerging role of intestinal permeability and mental health. Presented at: Psych Congress; Oct. 25-28, 2018; Orlando, Fla.

Disclosure: Scheiderer reports no relevant financial disclosures.