Knowing Neurons
Mental Health

Gut Microbiota & Mental Health

By Courtney Kremler

It’s a classic cycle that we have all been through before: craving pizza, sugar, or junk food of any kind, feeding that craving, promptly feeling worse, and doing it all over again. This cycle is at least partly attributable to our gut microbes, the bacteria and microorganisms living in our gastrointestinal tract, which dictate our cravings. These microbes can send out signals telling our brain we want chocolate cake, leaving us feeling powerless to resist. The problem is that feeding the wrong microbes can make us feel worse, as they release other signals that discourage exercise and healthy eating, ultimately causing a cycle of eating and feeling poorly (Dohnalová et al., 2022). The good news: as much as microbes dictate what we want to eat, what we actually eat dictates which microbes survive and — consequently — how we feel.

…different types of bacteria release different types of these signalling molecules, some with positive, mood-enhancing effects, and others that increase inflammation.

In order to feel both mentally and physically at our best, it is crucial to have a balanced gut microbiota (Verma et al., 2020; Dinan & Cryan, 2017). The gut microbiota, composed of the microorganisms living in our gastrointestinal tract, outnumbers our own cells with 1.3 bacterial cells per 1 human cell (Sender et al., 2016). Meanwhile, the microbiome, which refers to the genome of the previously mentioned gut bacterium, has 100-fold more genes than the human genome (Qin et al., 2010). Therefore, the impact these microbes have on our health is not to be understated. Indeed, the gut microbiota controls our mood and modulates both our physical and mental health by communicating with the brain and immune system. Hormones, metabolites, and chemicals known as neurotransmitters are released by microbes to communicate with the brain, while proteins known as cytokines are released by microbes to communicate with the immune system (Verma et al., 2020). Importantly, different types of bacteria release different types of these signalling molecules, some with positive, mood-enhancing effects, and others that increase inflammation. For example, microbes including Bifidobacterium and Lactobacillus release vitamins (vitamin B9, for example; Dohnalová et al., 2022), calming neurotransmitters (GABA and serotonin; Verma et al., 2020), and acetic acid, which protects against yeast and mould growth (Fukuda et al., 2011). These mediators all have positive effects on general health, and therefore, bacteria that produce them are termed probiotic. Importantly, some mediators, like GABA and serotonin, also have a positive impact on mental health, and bacteria that produce them are special probiotics, known as psychobiotics. The foods used to feed helpful bacteria are called prebiotics. However, some microbes, like Staphylococcus aureus (the same microbe that causes the common ‘Staph’ infection!), release toxins that compromise the gut lining and trigger inflammation (Kwak et al., 2012). Therefore, it is important to foster an environment that supports the growth of healthy bacteria.

The health consequences of an imbalanced gut microbiota are so profound that altering the microbiota is being investigated as a potential treatment for depression, anxiety, and irritable bowel syndrome (IBS).

The health consequences of an imbalanced gut microbiota are so profound that altering the microbiota is being investigated as a potential treatment for depression, anxiety, and irritable bowel syndrome (IBS). Patients with generalised anxiety disorder (GAD) had less short-chain fatty acid (SCFA)-producing bacteria and less microbial diversity than populations without GAD (Jiang et al., 2018). This is important as SCFAs have enormous health benefits, such as reducing inflammation and protecting against obesity, diabetes, and cancer, while microbial diversity is required to extract nutrients from a variety of food sources and provide resilience against infections (Lozupone et al., 2012; Xiong et al., 2022). Similarly, patients with depression have less SCFA-producing bacteria and less Bifido- and Lacto- species (Aizawa et al., 2016; Müller et al., 2021). However, these studies only demonstrate that there is a relationship between psychopathology and an unhealthy gut biota — they don’t establish which causes which. Experimental evidence shows that the gut biota really does influence our mental health and our ability to cope with stress. Treating depressed and anxious mice with Lactobacillus reduced their stress response, and patients with IBS show improved symptoms when taking probiotics (McKenzie et al., 2016; Bravo et al., 2011). Gut microbiota-based therapies offer a new therapeutic approach to these conditions that is desperately needed, even if only used in combination with more classical treatments, as the number of people experiencing mental health and inflammatory conditions in recent decades has greatly increased while treatment options have remained stagnant (Friedrich, 2017). The potential to treat mental health and inflammatory conditions with changes to the microbiota highlights the deep connection between mental and physical health and the gut microbiota.

It is not only patients suffering from mental and physical health conditions who can benefit from improving their gut microbiota, however; anyone who has an interest in improving their mood, energy levels, immune function, and overall health can do so with a few simple steps. The bacteria present in our gut depend on what we eat and do. Therefore, while one option to modulate the gut microbiota is to take probiotics and prebiotics, there are even easier and cheaper options that all focus on changing what we eat and do:

  • Eat fermented foods, like yogurt! Fermenting food encourages the growth of pre-existing probiotics, and eating fermented foods is associated with lower rates of depression (Kim & Shin, 2019; Inoguchi et al., 2011).
  • Eat your fruits and veggies. Fruits and vegetables (particularly whole grains such as quinoa and brown rice, as well as sunchokes, artichokes, chicory, endive, bananas and apples) contain soluble fibre, galactooligosaccharides (GOS), and fructooligosaccharides (FOS), which are natural prebiotics for helpful bacteria (Jacka et al., 2011; Costabile et al., 2008).
  • Increase diet diversity and eat fewer fatty foods. Eating a Norwegian-style diet, rich in fish, eggs, nuts, and poultry, is associated with lower levels of depression and anxiety than eating a western-style diet, rich in processed foods (Jacka et al., 2011).
  • Decrease your intake of added sugar. This means reducing the amount of processed food, including white bread, sausage, cola, and candy you eat. Foods with added sugar likely boost pathogenic bacteria (AKA, the kind that make you sick) and increase risk of depression (Kawano et al., 2022; Satokari, 2020).
  • Add food high in antioxidants. These include coffee, cocoa, and turmeric. Antioxidants increase levels of Bifido and Lacto, well-known psychobiotics (Queipo-Ortuño et al., 2012; Ghiamati Yazdi et al., 2019).
  • Exercise! Exercising increases the growth of health-promoting gut microbes such as Bifidobacterium and Lactobacillus (Bressa et al., 2017; Queipo-Ortuño et al., 2013).

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Are you going to try and implement any of the suggestions above? Let us know in the comments.

Read more about how gut bacteria can affect the brain in our article “Gut Feelings: The Connection With The Brain.”

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Written by Courtney Kremler
Illustrated by Federica Raguseo
Edited by Lauren Wagner, Shiri Spitz Siddiqi, and Keionna Newton

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Illustration showing food entering a intestine/brain hybrid

References

Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraishi, T., Yoshida, S., Ota, M., Koga, N., Hattori, K., & Kunugi, H. (2016). Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. Journal of Affective Disorders, 202, 254–257. https://doi.org/10.1016/j.jad.2016.05.038

Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050–16055. https://doi.org/10.1073/pnas.1102999108

Bressa, C., Bailén-Andrino, M., Pérez-Santiago, J., González-Soltero, R., Pérez, M., Montalvo-Lominchar, M. G., Maté-Muñoz, J. L., Domínguez, R., Moreno, D., & Larrosa, M. (2017). Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLOS ONE, 12(2), e0171352. https://doi.org/10.1371/journal.pone.0171352

Costabile, A., Klinder, A., Fava, F., Napolitano, A., Fogliano, V., Leonard, C., Gibson, G. R., & Tuohy, K. M. (2008). Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. The British Journal of Nutrition, 99(1), 110–120. https://doi.org/10.1017/S0007114507793923

Dinan, T. G., & Cryan, J. F. (2017). The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterology Clinics of North America, 46(1), 77–89. https://doi.org/10.1016/j.gtc.2016.09.007

Dohnalová, L., Lundgren, P., Carty, J. R. E., Goldstein, N., Wenski, S. L., Nanudorn, P., Thiengmag, S., Huang, K.-P., Litichevskiy, L., Descamps, H. C., Chellappa, K., Glassman, A., Kessler, S., Kim, J., Cox, T. O., Dmitrieva-Posocco, O., Wong, A. C., Allman, E. L., Ghosh, S., & Sharma, N. (2022). A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature, 612(7941). https://doi.org/10.1038/s41586-022-05525-z

Friedrich, M. J. (2017). Depression Is the Leading Cause of Disability Around the World. JAMA, 317(15), 1517. https://doi.org/10.1001/jama.2017.3826

Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., Taylor, T. D., Itoh, K., Kikuchi, J., Morita, H., Hattori, M., & Ohno, H. (2011). Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature, 469(7331), 543–547. https://doi.org/10.1038/nature09646

Ghiamati Yazdi, F., Soleimanian-Zad, S., van den Worm, E., & Folkerts, G. (2019). Turmeric Extract: Potential Use as a Prebiotic and Anti-Inflammatory Compound? Plant Foods for Human Nutrition, 74(3), 293–299. https://doi.org/10.1007/s11130-019-00733-x

Inoguchi, S., Ohashi, Y., Narai-Kanayama, A., Aso, K., Nakagaki, T., & Fujisawa, T. (2011). Effects of non-fermented and fermented soybean milk intake on faecal microbiota and faecal metabolites in humans. International Journal of Food Sciences and Nutrition, 63(4), 402–410. https://doi.org/10.3109/09637486.2011.630992

Jacka, F. N., Mykletun, A., Berk, M., Bjelland, I., & Tell, G. S. (2011). The Association Between Habitual Diet Quality and the Common Mental Disorders in Community-Dwelling Adults. Psychosomatic Medicine, 73(6), 483–490. https://doi.org/10.1097/psy.0b013e318222831a

Jiang, H., Zhang, X., Yu, Z., Zhang, Z., Deng, M., Zhao, J., & Ruan, B. (2018). Altered gut microbiota profile in patients with generalized anxiety disorder. Journal of Psychiatric Research, 104, 130–136. https://doi.org/10.1016/j.jpsychires.2018.07.007

Kawano, Y., Edwards, M., Huang, Y., Bilate, A. M., Araujo, L. P., Tanoue, T., Atarashi, K., Ladinsky, M. S., Reiner, S. L., Wang, H. H., Mucida, D., Honda, K., & Ivanov, I. I. (2022). Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Cell, 0(0). https://doi.org/10.1016/j.cell.2022.08.005

Kim, C.-S., & Shin, D.-M. (2019). Probiotic food consumption is associated with lower severity and prevalence of depression: A nationwide cross-sectional study. Nutrition, 63-64, 169–174. https://doi.org/10.1016/j.nut.2019.02.007

Kwak, Y.-K., Vikström, E., Magnusson, K.-E., Vécsey-Semjén, B., Colque-Navarro, P., & Möllby, R. (2012). The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity. Infection and Immunity, 80(5), 1670–1680. https://doi.org/10.1128/iai.00001-12

Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012). Diversity, stability and resilience of the human gut microbiota. Nature, 489(7415), 220–230. https://doi.org/10.1038/nature11550

McKenzie, Y. A., Thompson, J., Gulia, P., & Lomer, M. C. E. (2016). British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). Journal of Human Nutrition and Dietetics, 29(5), 576–592. https://doi.org/10.1111/jhn.12386

Müller, B., Rasmusson, A. J., Just, D., Jayarathna, S., Moazzami, A., Novicic, Z. K., & Cunningham, J. L. (2021). Fecal Short-Chain Fatty Acid Ratios as Related to Gastrointestinal and Depressive Symptoms in Young Adults. Psychosomatic Medicine, 83(7), 693–699. https://doi.org/10.1097/PSY.0000000000000965

Pompei, A., Cordisco, L., Amaretti, A., Zanoni, S., Matteuzzi, D., & Rossi, M. (2006). Folate Production by Bifidobacteria as a Potential Probiotic Property. Applied and Environmental Microbiology, 73(1), 179–185. https://doi.org/10.1128/aem.01763-06

Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D. R., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., & Xie, Y. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285), 59–65. https://doi.org/10.1038/nature08821

Queipo-Ortuño, M. I., Boto-Ordóñez, M., Murri, M., Gomez-Zumaquero, J. M., Clemente-Postigo, M., Estruch, R., Cardona Diaz, F., Andrés-Lacueva, C., & Tinahones, F. J. (2012). Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. The American Journal of Clinical Nutrition, 95(6), 1323–1334. https://doi.org/10.3945/ajcn.111.027847

Queipo-Ortuño, M. I., Seoane, L. M., Murri, M., Pardo, M., Gomez-Zumaquero, J. M., Cardona, F., Casanueva, F., & Tinahones, F. J. (2013). Gut Microbiota Composition in Male Rat Models under Different Nutritional Status and Physical Activity and Its Association with Serum Leptin and Ghrelin Levels. PLoS ONE, 8(5), e65465. https://doi.org/10.1371/journal.pone.0065465

Satokari, R. (2020). High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria. Nutrients, 12(5), 1348. https://doi.org/10.3390/nu12051348

Sender, R., Fuchs, S., & Milo, R. (2016). Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell, 164(3), 337–340. https://doi.org/10.1016/j.cell.2016.01.013

Verma, H., Phian, S., Lakra, P., Kaur, J., Subudhi, S., Lal, R., & Rawat, C. D. (2020). Human Gut Microbiota and Mental Health: Advancements and Challenges in Microbe-Based Therapeutic Interventions. Indian Journal of Microbiology, 60(4), 405–419. https://doi.org/10.1007/s12088-020-00898-z

Xiong, R.-G., Zhou, D.-D., Wu, S.-X., Huang, S.-Y., Saimaiti, A., Yang, Z.-J., Shang, A., Zhao, C.-N., Gan, R.-Y., & Li, H.-B. (2022). Health Benefits and Side Effects of Short-Chain Fatty Acids. Foods, 11(18), 2863. https://doi.org/10.3390/foods11182863

Author

  • Courtney Kremler

    'm a PhD student at the University of Cambridge studying Multiple Sclerosis (MS) and myelin-related biology. I received an integrated Masters and Bachelors in Neuroscience from the University of Bristol, which is where my interest in MS really developed. During my undergraduate degree I spent a year in industry at Sosei Heptares working on a remyelination-focused project, and in my PhD have moved to a more clinical perspective of MS; optimising treatments for affected patients. I'm really interested in understanding the different subtypes of MS that remain undiscovered, and how potentially different MS pathologies may be affecting patients response to different treatments. I use a combination of big data analysis and coding to explore this. I am also passionate about science communication and science policy.

Courtney Kremler

'm a PhD student at the University of Cambridge studying Multiple Sclerosis (MS) and myelin-related biology. I received an integrated Masters and Bachelors in Neuroscience from the University of Bristol, which is where my interest in MS really developed. During my undergraduate degree I spent a year in industry at Sosei Heptares working on a remyelination-focused project, and in my PhD have moved to a more clinical perspective of MS; optimising treatments for affected patients. I'm really interested in understanding the different subtypes of MS that remain undiscovered, and how potentially different MS pathologies may be affecting patients response to different treatments. I use a combination of big data analysis and coding to explore this. I am also passionate about science communication and science policy.