The Gut-Brain Axis
This is a topic that interested me particularly because I suffered from depression when I was younger for a good portion of my teenage years and early 20’s. We often said that depression and mental illness just “ran in our family”. An article in the New York Times in 2015 had a very interesting headline that caught my attention: “The rich array of microbiota in our intestines can tell us more than you might think” (Smith, 2015).
Recent studies indicate bacteria use signals to alter the biochemistry of the brain (Zimmer, 2014). However, this theory is not as recent as it seems. In fact, Julianelle & Ebaugh published a paper in 1923 about an investigation that was done to study the effects of B. acidophilus in milk on intestinal putrefaction. During those times, it was thought that the cause of mental illness was intestinal putrefaction and the cure was to surgically remove the colon (Greger, 2013). A different study in 1910 studied the treatment of “melancholia” using lactic acid bacillus (Greger, 2013). “Ranging from a mild attack of depression to a severe case of melancholia one finds the hub of the disturbance centring itself in the alimentary canal” (Phillips, 1910). According to the study by Phillips, lactic acid bacillus was helpful in depression (termed melancholy) by diminishing toxins absorbed from the intestinal tract and promoting better digestive assimilation (Phillips, 1910). So although they did not have the technology to appreciate the role of the microbiome, they were on the right track over 100 years ago!
It is the very microbiota in the gut that can affect the levels of neurotransmitters responsible for aspects of brain activity related to mood. Micro-organisms in the gut trickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety” (Smith, 2015). For example, they can influence the metabolism of tryptophan, the precursor of serotonin (“the happy hormone”) (Lyte, 2014). Other neurotransmitters produced by gut microbes include dopamine, norepinephrine, GABA, and acetylcholine (Lyte 2013). A change in any one of these neurotransmitters can alter our moods significantly! In fact anxiety, depression and several childhood disorders such as autism or ADHD have been linked with gastrointestinal abnormalities (Smith, 2015).
Some bacteria can actually promote behavioral disturbances. For example, campylobacter jejuni, a pathogenic bacteria found in contaminated poultry, can increase anxiety behaviors in the host (Goehler, Park, Opitz, Lyte, & Gaykema, 2008). Clostridium and Bacteroides species can produce propionic acid, a short chained fatty acid (SCFA) known to increase anxiety, aggression and social isolation in animals (Messaoudi et al., 2011). “The role of inflammatory processes on emotion is indicated by findings of a link between depression and elevated levels of IL-6, TNF and C-reactive protein” (Messaoudi et al., 2011)
I found it fascinating that brain levels of many neurotransmitters, like serotonin, are actually established early in life in utero and early childhood, significantly affecting their concentrations during adulthood (Clarke et al., 2013). This could be the link between stressful events during pregnancy and the implications on neurotransmitter profiles of children! (As I look in retrospect, my mother had a very difficult and stressful pregnancy with my brother, and his birth and early childhood was traumatic as he was hospitalized numerous times with multiple infections. He had his tonsils removed at an early age of 1 while having a pretty high fever).
Some neurotransmitters, like serotonin, can also regulate appetite, digestion and satiety, which may be a reason why many depressed individuals are also overweight. In fact, I recall having struggled with my weight and depression at the same time. Additionally, I notice that my moods improve when I fast. (This will be a topic for a future discussion in regards to fasting!) I also notice my appetite is suppressed when I am happy and ravenous when I am feeling “blue”.
So what are some of the solutions?
Probiotics- Probiotics are currently being evaluated for neurological conditions such as depression and anxiety, and the results are looking promising. Probiotic studies suggest that ingestion of Biﬁdobacteria or Lactobacilli can beneﬁcially alter anxiety or depressive-like behaviors. One probiotic formulation combining Lactobacillus helveticus and Bifidobacterium longum showed beneficial effects on GI symptoms in patients subjected to chronic stress (Messaoudi et al., 2011). helveticus demonstrated favorable activity on sleep efficiency in elderly subjects; l. casei improved mood scores and decreased anxiety for those with chronic fatigue syndrome (Messaoudi et al., 2011). Another strain of interest is l. rhamnosus which is known to release significant quantities of GABA. GABA is as an inhibitory neurotransmitter known to calm nervous activity (Smith, 2015). “The beneficial effects of probiotics on anxiety and depression may be explained by competitive exclusion of deleterious gut pathogens, decreases in pro-inflammatory cytokines and communication with the central nervous system via vagal sensory fibers, leading to changes in neurotransmitter levels or function” (Messaoudi et al., 2011). Probiotics may have some overall effects similar to antidepressants such as SSRI’s (Deans, 2016). In the study by Messaoudi et. al, daily administration of probiotics for 30 days significantly decreased urinary free cortisol levels in subjects under daily life events as a source of stress. An interesting study by Knowles examined college students during exam time and found that that faecal lactic acid bacterial levels were lower during the high-stress condition (Knowles, Nelson, & Palombo, 2008). (Maybe we should ramp up our probiotic dose during exam time!)
Nutrition –Another way to improve neurotransmitter function is through nutrition. “Nutrition, from as early as in utero, through the neonatal period, and up to adulthood, has a profound effect on the shape and trajectory of our intestinal microbiome” (Lerner, Neidhofer, & Matthias, 2017) Signiﬁcant changes in the gut microbiome have been primarily associated with the intake of ﬁber from fruits, vegetables and other plants. Fiber provides food for the good bacteria in our gut and promotes their growth, which is a good thing when trying to optimize neurotransmitter function (Lipski, 2013).
Mindfulness-Since the gut bacteria are negatively influenced by stress, its makes sense to implement mindfulness and stress reduction measures to optimize the microbiome. In fact, gestational stress can alter brain development in the fetus and increases the risk of emotional distance, communication and altered stress behaviors (Krishnan, 2017). I often ask myself during times of stress and anxiety, “how is this way of thinking affecting my health, microbiome and DNA expression?” I think there is definitely some room for improvement in this area, and I hope that in the near future we will see measures to reduce stress in conventional medicine therapy.
Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R. D., Shanahan, F., . . . Cryan, J. F. (2013). The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry, 18(6), 666-673. doi:10.1038/mp.2012.77
Deans, Emily. (2016, February 21). Probiotics for Depression. Retreived from https://www.psychologytoday.com/blog/evolutionary-psychiatry/201602/probiotics-depression
Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. (2008). Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun, 22(3), 354-366. doi:10.1016/j.bbi.2007.08.009
Greger, Micheal. (31, May 31st). Gut Feelings: Probiotics & Mental Health. Retrieved from https://nutritionfacts.org/video/gut-feelings-probiotics-and-mental-health/
Knowles, S. R., Nelson, E. A., & Palombo, E. A. (2008). Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibility to illness. Biol Psychol, 77(2), 132-137. doi:10.1016/j.biopsycho.2007.09.010
Latalova, K., Hajda, M., & Prasko, J. (2017). Can gut microbes play a role in mental disorders and their treatment? Psychiatr Danub, 29(1), 28-30.
Lerner, A., Neidhofer, S., & Matthias, T. (2017). The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists. Microorganisms, 5(4). doi:10.3390/microorganisms5040066
Lipski, E. (2013). Digestion Connection New York, NY: McGraw Hill.
Lyte, M. (2014). Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes, 5(3), 381-389. doi:10.4161/gmic.28682
Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., . . . Cazaubiel, J. M. (2011). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr, 105(5), 755-764. doi:10.1017/s0007114510004319
Phillips, George. (July 1910). The Treatment of Melancholia by the Lactic Acid Bacillus. Retrieved from https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8FFA58CD6E82E8F015379F1D30552CD4/S0368315X0012866Xa.pdf/div-class-title-the-treatment-of-melancholia-by-the-lactic-acid-bacillus-div.pdf
Smith, Peter. (2015, June 23). Can the Bacteria in Your Gut Explain Your Mood? Retrieved from https://www.nytimes.com/2015/06/28/magazine/can-the-bacteria-in-your-gut-explain-your-mood.html (Links to an external site.)
Zimmer, Carl. (2014, August 14). Our Microbes May be Looking Out for Itself. Retrieved from https://www.nytimes.com/2014/08/14/science/our-microbiome-may-be-looking-out-for-itself.html?_r=1 (Links to an external site.)