The gut microbiome, previously nicknamed the “forgotten organ,” has gained a new identity as the fix-all solution to health ailments. Despite being a buzzword in fad health trends, the gut microbiome has actually been shown to play acritical role in human health and disease. Most recently, research has implicated the connection between the gut microbiome and the brain (otherwise known as the gut-brain axis) as a target for therapies of the nervous system.
The gut-brain axis is a two-way communication system linking the central nervous system (comprising the brain and spinal cord) with the enteric nervous system in the gastrointestinal tract (1). Turns out, the enteric nervous system is actually the largest component of the autonomic nervous system, facilitating communication with the brain through neural, hormonal, and immune signaling pathways. Remarkably, these pathways can act as two-way streets allowing diseases acquired in or originating from the gut to spread to the brain, or diseases of the brain to have enteric manifestations (1).
The pathophysiology of some neurodegenerative disorders is a prime example of how the gut-brain axis can be related to neural dysfunction. Take α-synuclein aggregates, one of the key pathophysiological features associated with Parkinson’s Disease and some forms of Alzheimer’s Disease (2, 3). In Parkinson’s Disease, the aggregation of α-synuclein causes mitochondrial dysfunction in dopaminergic neurons, leading to the hallmark Parkinson’s tremors (4). In Alzheimer’s Disease, aggregation of α-synuclein creates Lewy Bodies that disrupt the neurons of the substantia nigra (5). Until recently, these aggregates were thought to originate exclusively in the brain, but several studies have confirmed that changes to the gastrointestinal microbiome cause misfolding and abnormal aggregation of α-synuclein in the intestine. These intestinal aggregates cannot be broken down by the body and are therefore transported into the brain via the vagus nerve (the primary neural connection on the gut-brain axis) (4).
The gut microbiome is also intricately intertwined with mood disorders. Serotonin is the neurotransmitter that creates feelings of focus, happiness, calmness, and emotional stability, hence why many mood disorders are linked to dysregulation in serotonin levels (6). Remarkably, over 90% of the serotonin in the human body is produced in the gut. From the gut, serotonin is transmitted to the CNS, thereby directly affecting emotional regulation (7). Given serotonin’s origin, gut health has been implicated in the dysregulation of neurotransmitter levels in the brain and body. In fact, a 2022 literature review examining the influence of dietary habits and interventions on psychiatric and neurological disorders states that “diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels” (8).
Unsurprisingly, biopharmaceutical companies have been paying close attention to these innovative discoveries and are increasingly leveraging the gut-brain axis for new therapeutic targets. Resulting therapies could win big in the wake of many unsuccessful attempts at treatments that slow or stop disease progression for uncurable nervous system conditions such as Alzheimer's Disease, Parkinson’s Disease, and Multiple Sclerosis.
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