Brain-Gut Axis In Neurodegenerative Disorder

Brain Awareness Week 2023
Series 4 of 7
Brain-Gut-Microbiota Axis In Neurodegenerative Disorders.

The Brain-Gut axis, is mediated by neuronal, immune, and neuroendocrine pathways. In the GI tract, certain gut microbiota can produce neuroactive substances, such as dopamine, serotonin and short-chain fatty acids. Signals from abnormal gut microbiota and its metabolites in a dysbiosed state of gut, can be sensed and transported by afferent fibers of Vagus nerve into the brain. In addition, the integrity of gut barrier being disrupted, these metabolites enter the circulatory system.
These substances can directly or indirectly activate the immune system to release inflammatory factors. Under the state of immune dysfunction, the permeability of the blood–brain barrier (BBB) is increased. Inflammatory factors and neuroactive substances produced by gut microbiota cross the BBB, leading to neuroinflammatory activation of hypothalamus-pituitary-adrenal axis and disrupt normal brain functions.
This is the overview of pathogenesis of neurodegenerative disorders like Parkinson’s, autism and bipolar conditions.

Parkinson’s disease

Parkinson’s disease (PD) is a chronic, progressive, neurological disorder affecting the motor system.
The pathological hallmark of PD is intraneuronal accumulations of misfolded alpha-synuclein, along with neuroinflammation, leading to dopaminergic neuronal degeneration in the substantia nigra.
Alteration of the gut microbiota composition in PD may accelerate α-synuclein aggregation, partly through the secretion of bacterial amyloid.
The gut microbial toxins like lipopolysaccarides(LPS) may induce the production of α-synuclein aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system.
Supplementation with pre- and probiotics, fecal microbiota transplantation, and dietary interventions, help reverse dysbiosis by altering the composition of the microbiome, modulate various biomolecules known to reduce inflammation and promote neurogenesis.

Autism (ASD)

Autism (ASD) is a highly heritable neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral, communication impairments, and gastrointestinal (GI) symptoms, such as constipation and diarrhea.
In individuals with ASD, microbiota dysbiosis promotes toxins and bacterial products to enter the bloodstream via a damaged intestinal barrier.
The brain, in turn, modulates gut peristalsis and sensory and secretion functions, linking sympathetic glutamatergic neurons in the CNS to the gut through the vagus nerve, which further impacts the gut-brain axis and trigger or escalate the incidence of ASD.
Consumption of beneficial microbes like probiotics, postbiotics and prebiotics help maintain healthy microbiome and increase short-chain fatty acids, they help improve brain function by inhibiting histone deacetylases and positively changes behavioral symptoms in individuals with ASD.
Microbial transfer therapy and fecal microbial transplantation can potentially treat autism-like symptoms, including the restoration of healthy gut microbiome composition.

Bipolar disorder

Bipolar disorder (BD) is a mood disorder, characterized by repeated episodes of major depression and mania (or hypomania), which subtypes include Bipolar type I and type II, the difference between which mainly lies in the severity of mania.
Neurotransmitter dysregulation is a major pathophysiological signature of BD (like, GABA, glutamate, serotonin, dopamine)
Gut microbiota is a central modulator of several of these neurotransmitters, being able to synthesize them and their precursors as well as promoting their degradation or metabolization to other products. Hence Gut-Brain axis plays is a major pathway in this condition.
The effect of psychiatric drugs on gut microbiota currently used in bipolar disorder patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) is promising inverventional therapy