Feeling Anxious? Maybe Not

Good for you. You’re going to Disney World. But don’t say you’re anxious about it. It’s okay to be anxious about going to the dentist. It’s understandable that you’d be anxious about your debut at an IRS audit. Unless you‘re terrified by the characters, you’re eager, not anxious, about visiting Walt’s place. To be anxious is to be afraid, apprehensive, uneasy, or distressed, but not enthusiastic. Anxiety is a disorder with more than one characterization. It can display as panic disorder, obsessive-compulsive disorder, post-traumatic-stress disorder, social anxiety, and a few others, including various phobias. It’s even possible to be anxious about being anxious, to the point that the subsequent distress precludes a normal life.

A common emotion, anxiety is felt by most humans once in a while. Taking a test, facing a novel problem at the office, or making a difficult decision is enough to get you anxious. Being lost in a strange town makes you feel like a rat in a laboratory maze. These little upsets are supposed to go away. If they cause a lingering burn, it’s time to talk about it. Frustration with a task can cause anxiety, and anxiety about doing it in the first place can cause frustration, which then perpetuates the cycle. Replacing uncomfortable cognitions with calming thoughts—something you can learn to do yourself—is one path to serenity.  The Roman Emperor Marcus Aurelius wrote about dealing with frustration and anxiety two thousand years ago. So, this isn’t a new challenge. However, what is new is the discovery that the ninety percent of the cells that compose the body have the potential to respond to anxiety. These would be the intestinal bacteria that have the uncanny ability to communicate with the brain, a conclusion attributed to evolution but more than likely decided at the ontogeny. That a bidirectional communication system between the gut and the cerebrum exists has been established, and that it influences brain development and behavior through complex signaling mechanisms is amply defined (Diaz-Heijtz, 2011) (Collins, 2012) (Chen, 2013).

The connection between gut and brain is controlled by the vagus nerve, which is the longest cranial nerve, passing through the neck and thorax into the abdomen, where it directs motor and secretory impulses of the viscera—your innards. Stimulation of this nerve can instigate activity in a body process known as the HPA axis (Hosoi, 2000) (O’Keane, 2005), the hypothalamic-pituitary-adrenal axis, the control center for most of the body’s hormones, one of which is the steroid hormone cortisol. Cortisol is used as a biomarker for psychological stress (Djuric, 2008).  In response to physical or mental stress, the hypothalamus produces corticotropin-releasing factor, which binds to specific receptors in the pituitary gland, where adrenocorticotropic hormone (ACTH) is made. ACTH then moves to the adrenals to direct the secretion of cortisol. The idea behind cortisol is to break down body tissue to be used as energy. When rampant, it breaks down lean tissue to liberate amino acids that can be used to raise blood sugar. In adipose tissue, cortisol breaks fats into fatty acids and glycerol, which also elevate blood sugar.

To calm this activity in a kind of physiological riot control, the body enlists the major inhibitory neurotransmitter, called gamma-aminobutyric acid—GABA—to slow down the firing of nerve cells in the brain. Emily Dean, M.D., a psychiatrist practicing in Massachusetts, likens GABA to a glass of wine in front of a fire, to restful sleep, or to tranquility and yoga (http://www.psychologytoday.com/blog/evolutionary-psychiatry/201206/do-probiotics-help-anxiety). Paints a nice picture, eh? Negative alterations in GABA receptor expression are implicated in the development of anxiety and depression, which are comorbid with functional bowel disorders.

It’s been hypothesized that probiotics are able to make compounds that enhance the brain-gut link by acting as delivery vehicles for neuroactive substances, with each neurochemical being related to a specific strain of intestinal flora (Lyte, 2011). The strain Lactobacillus rhamnosus is known to modulate the immune system by manipulating tumor necrosis factor alpha (TNFa) and Interleukin 8 (Ma, 2004), two cytokine signaling molecules related to immunity and inflammation. In mouse studies performed in Ireland a couple years back, those animals preloaded with L. rhamnosus were spared a frantic response to physiological insult and stress, contrasted to their cage mates denied the probiotic, whose cortisol levels were extreme (Bravo, 2011). As expected, mice whose vagus nerves were severed had no similar neurochemical and behavioral effects, indicating the vagus nerve as the major thoroughfare between gut bacteria and the brain (Ibid). Even in the absence of insult, mice treated with lactobacillus presented with higher levels of anxiety-reducing receptors, the observation of which could not be made until their sacrifice. A lactobacillus, then, reduces stress-induced levels of corticosterone (the rodent equivalent of cortisol) by normalizing the HPA axis (Gareau, 2007).

The HPA axis helps to regulate physiological processes that include temperature, digestion, immunity, mood, sexuality and energy usage, besides controlling your response to stress, trauma and injury. If, as believed, the hypothalamus is involved with fibromyalgia and the adrenals with chronic fatigue syndrome, the use of a probiotic to tend to the HPA axis should ameliorate these assaults. If GABA plays a major role in the HPA stress response (Herman, 2004) (Cullinan, 2008), and if GABA production is enhanced by lactic acid bacteria (Dhakal, 2012), then a five-dollar treatment for anxiety is at hand.  Not only L. rhamnosus, but also L. brevis (Li, 2010), L. reuteri (Ma, 2004), and strains of Bifidobacteria (Barrett, 2012) work to produce GABA. This should settle once and for all that not all bacteria are bad