“Butterflies in my stomach”

“I had a gut feeling”

“...my stomach dropped” 

“...a knot in the pit of my stomach”

These are common enough phrases, but the connection between our gut and anxiety is often overlooked or underappreciated. We feel the effects of the connection, but do not fully understand it, especially in relation to anxiety.

Anxiety is a common mental disorder. It is estimated that about 1 in 5 adults experience an anxiety disorder in any given year (Frye, 2019). If you or someone close to you has ever felt stressed, experienced general anxiety or worry, or been diagnosed with an anxiety disorder, it is likely that gastro-intestinal discomfort accompanied the experience. This can include heartburn, abdominal cramps, constipation, or loose stools. 

“More and more basic studies have indicated that gut microbiota can regulate brain function through the gut-brain axis, and dysbiosis of intestinal microbiota was related to anxiety” (Yang, Wei, Ju, & Chen, 2019).

The connection and communication between our brain and our gut is a two-way street. This two way communication between gut and brain, or between microbiome and human functions, is primarily done via the gut-brain axis. This refers to the chemical reactions that occur in the gut or brain that end up influencing the other. The channels used in this communication can include neurotransmitters, hormones, and neurotrophic substances. 

Here are some known factors between the gut and anxiety:

Corticotropin Releasing Factor (CRF)

This is a peptide that directs endocrine, behavioral, and gastro-intestinal responses to stress, for example, playing a role in directing the adrenal glands to release cortisol.  While CRF is valuable for appropriate responses to acute stress, an abundance of CRF, whether from chronic stress or imbalance gut microbiota, can lead to development of anxiety and depression. CRF also causes changes to the gastrointestinal system, which is one reason why during moments of intense stress or panic, people can experience the extremes of constipation or diarrhea, and why those suffering from chronic stress-related disorders such as anxiety and depression have gastrointestinal complaints. 

Lipopolysaccharide (LPS)

LPS is a natural coating of some bacteria, but it is treated as an endotoxin when it enters our bloodstream. It should stay in our gut- in fact most healthy humans have approximately 1 gram of it in our gut at any given time. If our intestinal lining is permeable, or has gaps, LPS can enter our bloodstream, causing an inflammatory response from our immune system. “LPS can damage the blood–brain barrier and consequently allow a large amount of potent substances to cross, such as environmental toxins, pathogens and even itself,” (Liu & Zhu, 2018). Inflammation induced by LPS causes a trickle down effect of multiple enzymes that leads to depression and anxiety. Yikes. 

Psychobiotics

Psychobiotic is a broad name for interventions to effect changes in mental health via modulation of the gut microbiome, including prebiotics, probiotics, diet, and exercise. For example, study participants taking a galacto-oligosaccharides prebiotic showed a decrease in attention to and focus on negative information versus positive information. In another study, both healthy subjects and subjects with anxiety showed improvements in mood when taking a probiotic product with multiple probiotic strains. Students in a study who took a Lactobacillus supplement showed lower cortisol in their blood compared to the control group. A recent review of anxiety studies showed that in clinical settings, probiotics were effective over half the time, and gut microbiome regulation overall (via probiotics, prebiotics, or diet) were effective over 80% of the time in reducing anxiety symptoms. More about each of these studies can be found in Yang, Wei, Ju, & Chen, 2019.

I would love to leave you with a hopeful and practical solution for anxiety and gastrointestinal issues. I cannot do so, nor am I your medical provider. Instead, I hope that you leave with a deepened appreciation for the complexity of the human body, and the intricate ways our microbiome affects our human experience. Even the small amount of evidence in this article illustrates how legitimate and pervasive mental disorders are. Chemical imbalances are not overcome by “sucking it up” or being told to just not be so sad or worried.

There is so much more to learn, and so many future breakthroughs to be made that will positively impact people’s lives. Perhaps you, or your child, or your student, will be the next scientist, journalist, doctor, or researchers to unlock a piece of the fascinating gut-brain puzzle!

TLDR: Interactions between the gut and brain are a two-way street. Anxiety and anxiety symptoms have some links to gut microbes and the gastro-intestinal system. Regulating the gut microbiome through probiotics and/or diet has been shown to help anxiety symptoms. While the connection between gut and brain, especially related to mental health, has been innately known for a long time, the true connections are beginning to emerge through research.

Sources and other info:

Binder, E., Nemeroff, C. (June, 2010). The CRF system, stress, depression and anxiety—insights from human genetic studies. Mol Psychiatry 15, 574–588. https://doi.org/10.1038/mp.2009.141 

Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., Guzzetta, K. E., Jaggar, M., Long-Smith, C. M., Lyte, J. M., Martin, J. A., Molinero-Perez, A., Moloney, G., Morelli, E., Morillas, E., O'Connor, R., Cruz-Pereira, J. S., Peterson, V. L., Rea, K., Ritz, N. L., Sherwin, E., Spichak, S., Teichman, E. M., Wouw, M. v. d., Ventura-Silva, A. P., Wallace-Fitzsimons, S. E., Hyland, N., Clarke, G. and Dinan, T. G. (2019). The microbiota-gut brain axis', Physiological Reviews, 99(4), pp. 1877-2013. https://cora.ucc.ie/bitstream/handle/10468/10506/MGBA_Review_KOR_09042019_Named.pdf?sequence=1   

Frye, D. (2019, December 17). From fear to guts: How the microbiome fights anxiety. https://www.psychologytoday.com/us/articles/201912/fear-guts-how-the-microbiome-fights-anxiety 

Jin, X., Zhang, Y., Celniker, S.E. et al. (2021). Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice. Sci Rep 11, 270. https://doi.org/10.1038/s41598-020-79538-x 

Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018). Anxiety, Depression, and the Microbiome: A Role for Gut Peptides. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(1), 36–59. https://doi.org/10.1007/s13311-017-0585-0 

Liu, L., & Zhu, G. (2018). Gut-Brain Axis and Mood Disorder. Frontiers in psychiatry, 9, 223. https://doi.org/10.3389/fpsyt.2018.00223 

Rodiño-Janeiro, B. K., Alonso-Cotoner, C., Pigrau, M., Lobo, B., Vicario, M., & Santos, J. (2015). Role of corticotropin-releasing factor in gastrointestinal permeability. Journal of neurogastroenterology and motility, 21(1), 33–50. https://doi.org/10.5056/jnm14084 

Yang, B., Wei, J., Ju, P., & Chen, J. (2019). Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review. General psychiatry, 32(2). https://doi.org/10.1136/gpsych-2019-100056