Gut Microbiota Influences on Anxiety and Depression
Alexandra L. Deaton
Mercer University
Abstract
The gut-brain axis provides a pathway to the brain from the intestines. This pathway can significantly alter emotional regulations. Consumption of prebiotics and probiotics has been linked to overall better intestinal health. Here we assessed the possible effects of probiotics in both females and males on depressive and anxious behavior. One thousand participants were followed over a 12-week time frame. Roughly half of the participants were given probiotic supplements beginning 3 days after baseline recordings, while the other half was given a placebo. After 12 weeks, participants given supplemental probiotics reported significantly lower levels of anxiety and depression than those given a placebo. There was also a significant difference recorded among gut microbiota within males and female participants. As of now, there is no conclusive data on why males and females show varying gut microbiota and how this diversity may contribute to anxious and depressive behaviors.
Keywords: Microbiota, Anxiety, Probiotics, Depression
Gut Microbiota Influences on Anxiety and Depression
There has been a relatively recent growth in the interest of microbiota effects on the developing brain and immune system. Numerous clinical observations have shown that during intrauterine development the gut and brain develop a strong relationship which can alter bodily functions throughout an individual’s lifespan (Borre et al., 2014). For reference, microbiome is used to refer to the genetic material of all microorganisms within the body, while microbiota can be used as a collective term of microorganisms within specific areas of the body (ex: the gut microbiota). Currently, the Human Microbiome Project (HMP), similar to the Human Genome Project, is being conducted in hopes to better understand the microbiotas that are involved in health and disease (Evrensel & Ceylan, 2015). Foster and Neufeld (2013) suggest that the gut microbiota play an essential role in how the body influences the brain, maintains a normal healthy homeostasis, and influences the risk of disease. The purpose of this proposal is to study if the reaction of increased use of probiotics decreases symptoms of anxiety and depression and how it varies among sexes due to a change in the gut microbiota.
Literature review
Over the years, there has been an increasing number of claims that dysbiosis of gut bacteria is linked to emotional and behavioral complications. Diets rich in prebiotics and probiotics have the potential to serve as a method of prevention and/or treatment of mental disorders such as anxiety and depression. Therefore, prebiotics and probiotics have been used both alone and in conjunction with prescription medications. Prebiotics and probiotics are easily found in fruits, vegetables (mainly asparagus), whole grains, yogurt, and fermented milks. Mika et al. (2018) studied the developing brain of rats while given diets high in prebiotics and probiotics. This study used formulated diets for the rats to ensure the prebiotic levels were met. Similarly, this proposal intends to put to use probiotic supplements to ensure that levels are met at a level that induces gut microbiota changes. The researchers also used an open field test to determine the possible change in anxious behavior. They found that the diet containing prebiotics did, in fact, alter brain activity and plasticity as well as decrease anxious behaviors in the open field test. Perez-Cornago et al. (2016) measured consumption of prebiotic and probiotic and the associated effects on depression in SUN graduates. This study collected the dietary information of graduates twice, while all other medical and lifestyle information was collected every two years. The dietary intake questionnaire is similar to one that will be used in this proposal, as well as self-reported personality, behavior, and medical diagnoses. However, the study by Perez-Cornago followed participants over a ten-year time frame and only checked dietary intake at the baseline and the ten year follow up periods. Cepeda, Katz, & Blacketer (2016) examined probiotics association with depression by use of a large cross-sectional study. This study recorded depressive behavior by means of the patient health question (PHQ-9). The researchers found that subjects subject to probiotic use were less likely to have depressive symptoms for mild or severe depression. Since this study did not explore the associations of probiotics with anxious behaviors, the proposed research will include the PHQ-9 as well as a questionnaire for generalized anxiety disorder (GAD).
Proposed Method
This study will be a mixed-factorial design, examining the effects of probiotics on depressive and anxious behaviors as well as the effects of probiotics in male and female gut microbiota. This study is being designed to assess the hypothesis that the gut microbiota varies significantly among males and females contributing to decreased levels of depressive and anxious behaviors due to an increased use of probiotic supplements.
Participants
For this study, one thousand (1000) participants will be recruited. Participants must be between the ages 18-25. Roughly half would be male, and the other half will be female. Information about the study will be given to family physicians and/or mental health professionals who could screen patients’ medical history to limit the number of confounds (medications, other disorders or illnesses). Through these outlets, physicians and mental health professionals will offer patients the opportunity to participate in this study. Outside patient information (health records, excluding the mental health disorder in question, sex, and gut microbiota levels) would not be documented. Personal information will be strictly kept between physicians and patients, so researchers will have no way of identifying patients based on information collected. Participants would be numbered based on treatment and sex (four groups total).
Procedure
The study follows participants’ levels of anxiety and/or depression over the course of 12 weeks. Levels of anxiety and/or depression would be self-identified in each participant by means of a questionnaire. This questionnaire will be administered as a pre-test given within the first 3 days of the study and as post-test given within the last 3 days of the study. A baseline of data for gut microbiota would also be recorded within the first 3 days of the study by means of stool samples, and this data would continue to be collected once every 4 weeks by the same measures. Physicians will send the stool samples to be analyzed using a mass spectrometry technique. The results would be sent back to physicians in which they would then redact any personal information and send to the researchers. For each sex, there is one group receiving the treatment (probiotics) and one group that receives a placebo. Both sexes will be grouped randomly. Participants, experimenters, and physicians are not to be made aware of which group receives treatment. Treatment type is revealed at the end of the experiment. Questionnaires will be given with informed consent.
Assessment of Depression
Depression will be measured by use of a self-reported screening tool from the Anxiety and Depression Association of America, the Patient Health Questionnaire (PHQ-9). This is 9-item questionnaire. Scores 0-4 represent no or minimal depression, scores 5-14 represent mild to moderate depression, and scores 15-27 represent moderately severe to severe depression. A sample of the screening tool is provided below.
Assessment of Anxiety
Anxiety will also be measured by use of a self-reported screening tool for Generalized Anxiety Disorder (GAD), known as GAD-7. This is a 7-item questionnaire. Scores 0-5 represent mild anxiety, scores 6-10 represent moderate anxiety, and scores 11-15 represent severe anxiety. A sample of the screening tool is provided on the following page.
Results
After 12 weeks, participants who were grouped with supplemental probiotics self-reported significantly lower scores of anxiety and depression on screening tools. There was also a significant difference in bacteria among male and female participants. However, there is little to support the reason behind the difference in bacteria and how it may contribute to anxiety and depression.
Discussion
There are some strengths and limitations within the proposed study. Strengths of this study include better control of some variables since health providers could prescreen participants and exclude any with potential health disorders outside of anxiety and depression. Another strength may be that complex equipment is needed for stool sample analysis, and there is a smaller chance of participant dropout given it is a short-term study. Limitations of this study include self-reported questionnaires. Participants may incorrectly answer if questions are misunderstood. Future research could focus on the gut microbiota differences among males and females given little is known on this topic.
References
Borre, Y. E., O’Keeffe, G. W., Clarke, G., Stantom, C., Dinan, T. G., & Cryan, J. F. (2014). Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Molecular Medicine, 20(9), 509-518. doi: 10.1016/j.molmed.2014.05.002
Evrensel, A., & Ceylan, M. E. (2015). The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience, 13(3), 239-244. doi: 10.9758/cpn.2015.13.3.239
Foster, J. A., & Neufeld, K. M. (2013). Gut-brain axis: How the microbiome influences anxiety and depression. Trends in Neurosciences, 36(5), 305-312. doi: 10.1016/j.tins.2013.01.005
Mika, A., Gaffney, M., Roller, R., Hills, A., Bouchet, C. A., Hulen, K. A., … Fleshner, M. (2018). Research article: Feeding the developing brain: Juvenile rats fed diet rich in prebiotics and bioactive milk fractions exhibit reduced anxiety-related behavior and modified gene expression in emotion circuits. Neuroscience Letters, 677, 103-109. doi:10.1016/j.neulet.2018.01.052
Perez-Cornago, A., Sanches-Villegas, A., Bes-Rastrollo, M., Gea, A., Molero, P., Lahortiga-Ramos, F., & Martínez-González, M.A. (2016). Intake of High-Fat Yogurt, but Not of Low-Fat Yogurt or Prebiotics, Is Related to Lower Risk of Depression in Women of the SUN Corhort Study. The Journal of Nutrition, 146(9), 1731-1739. doi: 10.3945/jn.116.233858
Spitzer, R.L., Kroenke, K., Williams, J. B., & Löwe, B. (2006). A Brief Measure for Assessing Generalized Anxiety Disorder. Archives of Internal Medicine, 166(10), 1092. doi: 166.10.1092
Temming, M. (2017). How bugs in your gut might hijack your emotions: Tiny molecules in the brain may help gut bacteria control anxiety levels, research suggests. Science News for Students, 1. Retrieved from http://proxy-s.mercer.edu/login?qurl=http%3a%2f%2fsearch.ebscohost.com%2flogin.aspx%3fdirect%3dtrue%26db%3dmih%26AN%3d125824550%26site%3deds-live%26scope%3dsite