Probiotics and the Vagus Nerve

Probiotics and the Vagus Nerve – a New Frontier for Psychiatric Conditions

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The vagus nerve plays a critical role in influencing the parasympathetic nervous system. Its activation influences the stress response, mood, immune function, digestion, heart rate, and can modulate the monoaminergic brain system. It also serves as the chief link between the gastrointestinal tract and the brain in a relationship known as the brain-gut axis. These roles mean the vagus nerve is a modulator of various psychiatric conditions such as depression, anxiety, and post-traumatic stress disorder (PTSD), which are increasingly being linked to gastrointestinal problems and inflammation.

Vagal nerve stimulation is well cited in various observational studies as a safe and effective treatment modality for psychiatric conditions including depression. (1) In fact, a European multicenter study showed that vagal nerve stimulation over a period of 3 months resulted in “a response rate of 37 percent and a remission rate of 17% percent. After 1 year of treatment, the response rate reached 53 percent and the remission rate reached 33 percent” in treatment-resistant patients with depression. (1) The pathophysiology of depression includes a dysfunctional HPA axis, inflammation, and imbalances with monoamine transmission, all of which can be regulated by vagal activity.

Vagal nerve stimulation can modulate monoamine metabolism by raising the levels of serotonin, norepinephrine, and dopamine. It has inhibitory action on the production of proinflammatory cytokines and TNF-α, which are increased in clinical depression, and a corresponding stimulatory action on the production of anti-inflammatory compounds. Finally, vagal nerve stimulation decreases corticotropin releasing hormone to modulate the HPA axis. Collectively, these actions positively affect mood and psychological state.

The gut microbiota has significant influence over the activity of the vagus nerve, working through neuroendocrine and metabolic mechanisms. Various studies have focused on the effect of specific probiotic strains for the purpose of improving mood and psychiatric conditions. For example, a common lactic acid bacteria, Lactobacillus rhamnosus, was found to alter GABAB1b  and GABAAα2 mRNA expression to combat GABA changes implicated in the pathophysiology of anxiety and depression. (2) Further, L. rhamnosus reduced stress-induced corticosterone which resulted in improvements in anxiety- and depression-related behavior. (2) These positive interactions between lactic acid bacteria in the gut and the brain occur only via the vagus nerve.

In another study, administration of the probiotic Bifidobacterium longum resulted in anxiolytic effects but these effects were dependent upon vagal nerve integrity, indicating its role as mediator between microbiota and psychiatric conditions. (3)

The afferent neurons of the vagus nerve are the targets by which neuroactive bacteria such as L. rhamnosus and B. longum transmit microbial messages to the brain. The vagus nerve contains 80 and 20 percent of afferent and efferent fibers, respectively. A healthy microbiota produces copious amounts of short-chain fatty acids, such as butyric acid, which directly activate afferent vagal terminals and send messages from the gut to the brain. (3) However, live bacterial species are not the only requirement for bacterial vagal nerve stimulation. As evidenced by B. fragilis, a lipid-free polysaccharide is both necessary and sufficient for activation of vagal afferent neurons. (4) Toll-like receptor 4 (TLR4) are expressed on vagal afferent fibers and can sense bacterial products such as lipopolysaccharides (LPS) to activate both the afferent fibers and the brain. (5)

Depression, anxiety, and other psychiatric conditions continue to plague a large percentage of the population and often, the default treatment is pharmaceutical drugs with undesirable side-effects. However, as researchers continue to unlock the mysteries of the vagus nerve and are finding it to be an important contributor to many of the underlying metabolic and neurohormonal problems associated with mood and cognitive function, the focus is shifting toward how practitioners can optimize vagal activity as a foundational solution to many common psychiatric conditions. At the same time, research is pointing to strong links between the gut microbiome and mental health. We are beginning to understand that the microbiome may be the target for optimizing vagal activity, and hence, improving depression, anxiety and other common psychiatric conditions.