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By Michalina Hanzel, PhD
The microbiota-gut-brain axis is a bidirectional relationship between the central and enteric nervous systems, which is heavily influenced by the microorganisms living in the gut. Accumulating evidence has pointed to the microbiome, composed mostly of bacteria, but also including archaea, fungi and viruses, as instrumental in maintaining human physiological functions.1 Importantly, the brain is influenced by various bacterial metabolites, capable of benefiting, and sometimes harming, their host - us.
Microbes in the gut have evolved in a symbiotic relationship with humans for millennia and can contribute to, and alter, various human physiological and pathological states. Their beneficial roles range from maintaining a balanced immune system to fermenting and digesting our food and producing mood altering substances. Remarkably, each person’s gut contains around 1kg of bacteria and the number of bacterial genes is ten times higher than our own. The composition of the human gut microbiota, initially inherited at birth, changes throughout life and depends on dietary habits, environmental signals, stress and many other factors.
Early studies on the interaction between the gut microbiota and the brain were focused on disorders of the digestive function and satiety, yet even those initial reports have cited high rates of comorbidity between gastrointestinal and psychiatric illnesses. For example, there is a strong correlation between irritable bowel syndrome and anxiety and depression in patients. More recent studies have shown that mice with different strains of bacteria exhibit different levels of anxiety, and human cirrhotic patients’ cognition is linked to their mucosal microbiota. Germ- free mice or animals treated with broad-range antibiotics also exhibit markedly different neurological phenotypes and neurotransmitter levels.2
In recent years, microbiota has also been investigated as a co-factor in the development of autism spectrum disorder (ASD), a heterogenous neurodevelopmental disorder that impairs a child’s ability to communicate and interact with others. Accumulating evidence suggests that the gut microbiota is associated with ASD symptoms partly through its influence on the immune system and metabolism 3. Gut dysbiosis has been widely demonstrated in ASD patients with both gastrointestinal (GI) and neurobehavioral symptoms; severity of gastrointestinal tract problems often correlate with severity of ASD symptoms. ASD patients also display abnormal intestinal permeability resulting in a higher antigenic load from the GI tract that travels to the brain and across the blood-brain barrier and influences brain function.
Learn more about the anatomy and physiology of the blood-brain barrier and access resources to study the cells and molecules controlling blood-brain barrier permeability .
Currently, a single distinctive profile of microbiota composition in ASD patients is unknown, but it is frequently less diverse than those of healthy children. ASD patients might also harbor higher levels of harmful bacteria that produce neurotoxins. Probiotics4 and fecal transplants5 have both been suggested for treatment of ASD patients with some success, but more clinical trials will need to be performed to show their effectiveness.
Michalina Hanzel, PhD
Postdoctoral Associate at The Rockefeller University
Dr. Hanzel is currently studying synaptic function in the cerebellum to understand neurodevelopmental disorders and has a background in developmental neurobiology, molecular and cell biology.
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