How the gut microbiome affects mood

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By Carolina Brooks, BA, IFMCP

Over two thousand years ago, Hippocrates famously declared that all disease begins in the gut. Although I do not aggressively start wiping out potential pathogens with large doses of antimicrobials straight off the bat with my patients, I always start by correcting nutrient assimilation, optimizing immune stability, and supporting proper digestive function. As clinicians, we must understand some of the mechanisms behind how the microbiome is able to modify brain function, so we can effectively support patients in making and breaking down neurotransmitters correctly.

A 2014 paper in Advances in Experimental Medicine and Biology discussed the role of probiotics as a therapeutic strategy for neuropsychological conditions. Several species of bacteria are involved in producing neurotransmitters, such as gamma-aminobutyric acid (GABA), dopamine, norepinephrine, acetylcholine, and serotonin by strains of Lactobacilli, Bifidobacterium, Escherichia, Saccharomyces, Streptococcus, Enterococcus, and Bacillus.

There is potential ability of these bacterially secreted neurotransmitters to influence brain behavior and function of the host. A 2020 review  discussed the production of B vitamins by the gut microbiome, which play a role in mitochondrial function as well as neurotransmitter production and breakdown.

Useful markers to look at in an organic acids test to understand serotonin production are the tryptophan metabolites quinolinic acid, kynurenic acid, and 5-hydroxyindoleacetic acid (5-HIAA). Quinolinic acid is a neuroexcitoxin produced from tryptophan after passing through the kynurenic acid pathway. This pathway is induced by cortisol or increased inflammatory cytokines, often produced by endotoxins. A 2011 review published in the Journal of Neuroinflammation concluded that increased quinolinic acid is associated with severe depression, microglial activation and neuroinflammation, and a reduction of bioavailability of tryptophan for serotonin synthesis. Tryptophan requires tetrahydrobiopterin and iron to be converted into 5-hydroxytryptophan (5-HTP) and then requires pyridoxine (vitamin B6) to make serotonin. 

Fat malabsorption may also play a significant role as vitamin D deficiency is the rate-limiting step for the synthesis of serotonin from tryptophan, and if cholagogue activity is sluggish, it may be worth considering taurine or tauroursodeoxycholic acid (TUDCA), which supports bile production. Studies have looked at taurine’s antidepressant effect and concluded that taurine may be involved in the regulation of the hypothalamic-pituitary-adrenal axis.

Additionally, a high saturated fat, low fiber diet may increase lipopolysaccharide (LPS) production in the gut, activate intestinal mucosal mast cells and cause endotoxemia, which can then increase gut permeability. A 2017 study in the journal Gut demonstrated that depressed patients often have high plasma levels of lipopolysaccharides.

Increasing plant fibers and omega-three fatty acid sources are a useful supplement al strategy to downregulate inflammation and reduce absorption of LPS. A 2015 study in the journal Psychopharmacology also demonstrated that prebiotic galactooligosaccharide (GOS) supplementation has been shown to improve salivary cortisol awakening response and reduce feelings of anxiety.

Butyrate in the gut helps to maintain the integrity of the gut wall and inhibit endotoxin absorption. It is a key supplement I prescribe in my practice as it also helps to support blood sugar regulation and improve insulin sensitivity. Along with probiotics, it is able to modulate brain derived neurotrophic factor (BDNF) function in the brain. Combining fructooligosaccharides (FOS) with GOS may also have a positive impact on BDNF and improve central serotonin levels. 

I recently started seeing a patient with a significant history of trauma and disordered eating, as well as current anxiety and depression. She was still breastfeeding, the birth of her second child had been extremely traumatic, and she had been unable to work for six months. Her previous practitioner had tested her for small intestinal bacterial overgrowth, for which she was positive. They had done an organic acid test, advised her to start a restrictive diet, and had supplemented the patient in accordance with the deficiencies she presented with on the test. She had not experienced any improvement with this protocol.

My approach, in contrast, was to put the patient on core digestive support to ensure she was assimilating nutrients, a high dose of fish oil, a prebiotic fiber blend to include both GOS and FOS, short-chain fatty acids, a probiotic blend including specific strains of Lactobacillus rhamnosus, and a prenatal multi-nutrient.

I also advised her to open her diet to include more fiber-rich plant foods with the view of diversifying her microbiome. If someone has a history of disordered eating, I do not advise eliminating large numbers of foods, but prefer to address this more aggressively with supplements and herbs.

Additionally, I also used two different tea blends containing herbs which are safe during breastfeeding to gently support her digestive health, which included herbs such as Plantago major (plantain), Foeniculum vulgare (fennel), Matricaria recutita (chamomile), Ribes nigrum (blackcurrant leaf), and Pimpinella anisum (anise). I recommended various stress management strategies, which did not exacerbate her anxiety like meditation did. We also did weekly frequency-specific microcurrent sessions to support vagal tone, improve digestive secretions, and downregulate the sympathetic nervous system response. Within a month, her digestion had improved to the point where she no longer appeared bloated daily, and her mood and anxiety had improved significantly, and she was able to return to work.

References

Schmidt, K., Cowen, P. J., Harmer, C. J., Tzortzis, G., Errington, S., and Burnet, P. W. (2015) Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology. Retrieved from: https://doi.org/10.1007/s00213-014-3810-0

Steiner, J., Walter, M., Gos, T., Guillemin, G.J., Bernstein, H, Sarnyai, Z., Mawrin, C., Brisch, R., Bielau, H., Meyer zu Schwabedissen, L., Bogerts., B, and Myint A. (2011) Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? Journal of Neuroinflammation. Retrieved from: https://doi.org/10.1186/1742-2094-8-94

Stevens, B. R., Goel, R., Seungbum, K., Richards, E. M., Holbert, R. C., Pepine, C. J., and Raizada, M. K. (2018) Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut. Retrieved from: https://doi.org/10.1136/gutjnl-2017-314759

Uebanso, T., Shimohata, T., Mawatari, K., and Takahashi, A. (2020) Functional Roles of B‐Vitamins in the Gut and Gut Microbiome. Molecular Nutrition Food Research. Retrieved from:  https://doi.org/10.1002/mnfr.202000426

Wall, R., Cryan, J. F., Ross, R. P., Fitzgerald, G. F., Dinan, T. G., and Stanton, C. (2014) Bacterial neuroactive compounds produced by psychobiotics. Advances in experimental medicine and biology. Retrieved from: https://doi.org/10.1007/978-1-4939-0897-4_10

Wu, G. F., Ren, S., Tang, R. Y., Xu, C., Zhou, J. Q., Lin, S. M., Feng, Y., Yang, Q. H., Hu, J. M., and Yang, J. C. (2017) Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats. Scientific reports. Retrieved from: https://doi.org/10.1038/s41598-017-05051-3