Gordon P, Maiden J, Stewart D, Jackson P. Trusting my gut feeling: exploring the connection between the gut microbiome and depression. HPHR. 2023;62. DOI: 10.54111/0001/JJJ11
Recent scientific advancements have illuminated the relationship between the gut microbiome and its profound implications on human health. Beyond its traditional roles in digestion and immunity, the gut microbiome has emerged as a pivotal player in influencing various physiological processes, including those relevant to mental health. Particularly intriguing is the exploration of potential connections between the gut microbiome and depression, a prevalent and debilitating global mental health disorder. This conceptual article explores the multifaceted relationship between the gut microbiome and depression, shedding light on its underlying mechanisms and unveiling its potential implications and recommendations for mental health providers.
Emerging research indicates a strong connection between gut microbiome and mental health, specifically depression. While traditionally associated with neurotransmitters in the brain, recent studies suggest that gut health might also play a crucial role in the diverse physiological processes related to depression1 and well-being. Specifically, inquiries into this potential correlation have revealed a complex relationship that may have implications for researchers, medical practitioners, and mental health clinicians addressing gut and mental health.2 Depression, a prevalent mental health disorder affecting millions worldwide, is characterized by persistent sadness, lethargy, and a loss of interest or pleasure in activities. Major depressive disorder (MDD) is a severe mood disorder, and individuals who struggle with depression experience chronic sadness and hopelessness.1 MDD is associated with high mortality, which is accounted for by suicide. It is estimated that over 700,000 people die by suicide each year, and a substantial proportion of these cases can be linked to underlying depressive conditions.3 While the precise reasons behind MDD are complex and involve multiple factors, researchers are now investigating the potential role of the gut microbiome in either promoting, exacerbating, or alleviating this debilitating mental health condition.
This conceptual article investigates the gut microbiome’s and MDD’s relationship, shedding light on its potential implications. Additionally, the article provides recommendations for mental health providers working with clients whose depression may be influenced by their gut microbiome. By examining current research, elucidating key mechanisms, and considering the broader context of mental health, we aim to contribute to the evolving discourse surrounding the impact of gut health on depression.
The gut microbiome encompasses a network of trillions of microorganisms and their genetic components residing within the confines of the small intestines within the gastrointestinal (GI) tract.4 Predominantly consisting of bacteria, this complex microbiome plays a pivotal role in an array of fundamental functions critical to overall health and vitality. Among these essential roles, the microbiome actively participates in the breakdown of ingested foods and the assimilation and production of essential nutrients.
Beyond its primary functions, the gut microbiome bacteria are engaged in a spectrum of other indispensable processes extending well beyond the digestive system’s confines. These encompass functions as diverse as metabolic processes, regulating body weight, bolstering immune responses, modulating brain activity, and influencing emotional states.4 Thus, individuals with depression due to poor gut health may experience heightened irritability and anxiety, affecting their interactions with others. At the same time, the accompanying fatigue and emotional exhaustion can disrupt their ability to manage and experience a wide range of emotions effectively.
The gut microbiota is composed of different bacteria species taxonomically classified by genus, family, order, and phyla. 1 Researchers state that defining what constitutes a healthy gut microbiome is a complex undertaking, fraught with substantial challenges.5 Chief among these challenges is the intrinsic uniqueness of an individual’s microbiome, sculpted by a constellation of factors encompassing genetics, dietary choices, and lifestyle. Moreover, sex-based disparities have emerged as noteworthy facets in microbiome research, as evidenced by studies revealing discernible distinctions in the gut microbiota of male and female mice. Gut health also exhibits sexual dimorphism, with discernible disparities between males and females. Within these gender-based distinctions, the spectrum of variations encompasses fluctuations in the relative abundance of specific bacterial taxa, a phenomenon intricately linked with the oscillatory dynamics of sex hormones, notably estrogen, and testosterone. The hormonal dynamics assume pivotal significance across diverse life stages, encompassing puberty, menstruation, pregnancy, and menopause.5 Given the multifaceted intricacies inherent to this relationship, pursuing a universally applicable definition of a healthy gut microbiome remains a formidable endeavor. The profound tapestry of microbial diversity exhibited across individuals eludes facile categorization, further underscoring the complexities inherent to this field of research.
There are several factors come into play in fostering a healthy gut microbiome, some of which commence prior to birth.6 These factors encompass:
Recent studies, although necessitating further exploration, highlight the presence of microorganisms in the placenta, amniotic fluid, and umbilical cord. This suggests that bacteria-rich amniotic fluid ingested by the fetus in utero aids in populating its digestive tract.
Natural birth exposes newborns to a diverse array of microorganisms within the vaginal cavity, contributing to the colonization of the digestive tract.
Human breast milk, containing a myriad of essential bacterial species, plays a pivotal role in shaping an infant’s healthy gut microbiome.
These factors wield influence over the diversity and overall constitution of the gut microbiome. A study comparing white and Chinese subjects in both the United States and Hong Kong reported distinct microbial compositions between countries and within the same nation based on ethnicities. This finding underscores the complexity of factors influencing gut microbiome diversity, including geographic location, lifestyle, and genetics. It highlights that many factors beyond ethnicity alone influence variations in gut microbiota.7
A well-rounded diet rich in fiber from fruits, vegetables, and other plant-based foods, along with probiotic-rich foods, supports the development and maintenance of the gut microbiome. Moreover, a diverse diet contributes to a varied gut microbiome.
Prolonged stress, whether psychological or physical, triggers a hyper-aroused state in the body. This, in turn, repeatedly activates the hypothalamic-pituitary-adrenal (HPA) axis, causing hormonal responses such as the releasphin-releasing hormone (CRH) by the hypothalamus. CRH stimulates the pituitary gland to release adrenocorticotrophic hormone (ACTH), ultimately leading to cortisol synthesis. Catecholamines are also released following stressors. Chronic stress profoundly affects the gut microbiome’s sensitivity to stress and its mediators, potentially impacting its health and ongoing development.
Certain medications, particularly antibiotics, can exert adverse effects on the health and growth of the gut microbiome. Even after antibiotic treatment ceases, its impact lingers as these therapies target pathogenic microorganisms and host-associated microbial communities in the gut.
The aging process is accompanied by declines in dentition, salivary function, digestion, and intestinal transit time. These age-related changes can affect the health of gut microbiota. Older individuals exhibit differences in microbiome composition compared to younger adults, with higher proportions of Bacteroidetes and lower proportions of Firmicutes. Notable reductions in Bifidobacteria, Bacteroides, and Clostridium cluster IV have been observed in individuals 60 and older.6
The complex dynamics of the gut microbiome and its significance for human health are underscored by the multifaceted factors contributing to its formation and maintenance. Understanding these influences provides valuable insights into fostering a healthy gut microbiome, which plays a pivotal role in overall well-being and disease prevention.
The connection between the brain and the gut is called the gut-brain axis (GBA), which has long been recognized as a pivotal factor in maintaining overall physiological balance. However, recent years have marked a significant shift in the scientific landscape, with the gut microbiome emerging as a fundamental influencer of gut-brain function.8 This understanding has led to acknowledging a distinct microbiota-gut-brain axis (MGBA), gaining traction, particularly in studying psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders.
As research on the MGBA has evolved, so has the comprehension of the complexities underlying this relationship. Researchers initially surmised that communication between the brain and the microbiome was unidirectional, with the brain solely influencing the dialogue. However, studies in recent years have indicated that communication between the brain and the gut occurs in a bidirectional manner, each potentially impacting the other’s functions.9 Furthermore, empirical evidence suggests a correlation between the composition of the gut microbiome and both neural activity and brain structure in humans, as demonstrated by functional and structural magnetic resonance imaging.10
This paradigm shift raises a central question of how communication between the gut microbiome and the brain transpires. Researchers postulate that the bidirectional communication within the MGBA occurs through both the central and enteric nervous systems. This network links emotional and cognitive brain centers with peripheral intestinal functions through neural, endocrine, immune, and humoral pathways. In a similar vein, another group of researchers in 2019 holds a parallel viewpoint, elaborating on the communication mechanisms. They suggest that this interaction involves a variety of pathways, such as the immune system, tryptophan metabolism, the vagus nerve, and the enteric nervous system. This complex interplay also involves microbial metabolites such as short-chain fatty acids, branched-chain amino acids, and peptidoglycans.8
The evolving understanding of the MGBA underscores the complex interdependence between the gut microbiome and brain health. This bidirectional communication, facilitated through multiple pathways and mechanisms, illuminates the pivotal role of the gut-brain axis in influencing a wide range of physiological and psychological processes. As ongoing research reveals the nuances of this relationship, the potential implications for various aspects of human health and well-being become increasingly evident.
A dynamic interaction occurs between the host and the gut microbiome in healthy individuals, establishing a harmonious equilibrium of bacteria crucial for maintaining the gastrointestinal tract’s well-being. This symbiotic environment prevents the proliferation of potentially harmful bacteria. The gut microbiome maintains a commensal relationship with the host; the microbiome flourishes in the nutrient-rich gut environment while conferring various benefits to the host.12
However, when alterations in microbial composition disrupt this delicate balance, a condition known as “dysbiosis” arises. Dysbiosis signifies an imbalance in gut microbiota homeostasis arising from changes in functional composition, metabolic activities, or distribution.12 This imbalance can manifest in three primary forms: 1) loss of beneficial organisms, 2) excessive growth of potentially harmful organisms, and 3) reduced overall microbial diversity. Notably, these categories can intersect, often occurring concurrently.
The significance of dysbiosis within this review pertains to its potential link to depression. In a study involving 552 patients with and without dysbiosis, the researchers identified dysbiosis as a risk factor for developing depression within five years after the index date. The risk was more pronounced in males, with 20.5% of individuals with dysbiosis diagnosed with depression compared to 5.5% without dysbiosis. This association was observed to be stronger in older individuals (>60 years).13
Corroborating these findings, researchers highlighted that while much of the understanding of the MGBA originates from preclinical studies, recent human research supports the role of specific bacterial genera, such as Bifidobacterium and Lactobacillus, in mood regulation. Reduced levels of these bacteria have been associated with MDD.14
In 2019, a systematic review was conducted on connections between MDD and the gut microbiome, especially in studies centered on inflammatory conditions and gut barrier health.15 Animal studies have further supported the potential causative role of dysbiosis in depression-like behaviors, as evidenced by antibiotic-induced dysbiosis leading to depression-like symptoms.
In 2022, another research study reinforced the idea that dysbiosis plays a crucial role in the development of MDD.16 According to researchers, dysbiosis contributes to the progression of MDD by impacting various aspects of the MGBA, such as immune system activation and disruption of critical gut-brain communication.16
It is important to recognize that the impact of dysbiosis extends beyond MDD. Researchers have observed that a growing body of evidence links gut dysbiosis to an array of mental health and neurocognitive disorders, encompassing anxiety, bipolar disorder, schizophrenia, dementia, and post-traumatic stress disorder. These associations are established through the intricate pathways of the MGBA.17
The pathophysiology linking dysbiosis and the emergence and trajectory of MDD is characterized by complexity, yielding analogous yet diverse interpretations. One prominent theory suggests that the modulation prompted by dysbiosis and its resultant products, including lipopolysaccharides (bacterial toxins composed of lipids and polysaccharides), influence neurotransmitters and assorted processes through the vagus nerve. Moreover, microbial immunomodulation can give rise to neuroinflammation, imparting discernible effects on behavior and mood.13 The heightened prevalence of depression among individuals grappling with dysbiosis lends credence to this proposition, as studies have indicated that depressive symptoms manifest in 20-40% of chronic inflammatory bowel disease patients.
Furthermore, researchers contend that the equilibrium between diverse competing gut microbiota species holds sway over neural function beyond mere regulation by the brain. This influence operates directly through the vagus nerve and indirectly via the immune system, neurotransmitter synthesis, endocrine functions (e.g., sex, stress, and thyroid hormones), and other signaling molecules.14
Dysbiosis can instigate inflammation within the gastrointestinal tract, amplifying stress on the microbiome by releasing cytokines and neurotransmitters. Coupled with increased intestinal permeability or leaky gut due to dysbiosis, these molecules disseminate systemically into the bloodstream. Elevated blood concentrations of cytokines such as TNF-a and MCP (monocyte chemoattractant protein) can accentuate blood-brain barrier permeability. Consequently, the blood-brain barrier’s permeability intensifies anomalous molecules’ impact, including lipopolysaccharides originating from the permeable gut. This, in turn, influences brain function, potentially giving rise to anxiety, depression, and memory impairments.18
The surge in interest surrounding the gut microbiome, driven by its ties to overall well-being, has led to a heightened focus on specific dietary components and supplements that can foster a thriving gut microbiome.6 This prompts consideration of whether bolstering the growth and sustainability of a healthy gut microbiome should be an integral facet of managing MDD. Given the established correlation between gut dysbiosis and varying degrees of depression, it seems reasonable to posit an affirmative response to this question. Notably, human trials exploring the augmentation of gut bifidobacteria and lactobacilli through probiotic, prebiotic, and synbiotic interventions have yielded promising outcomes in alleviating symptoms of depression and anxiety within both non-clinical and clinical populations.14 However, it is noteworthy that some extensive trials have arrived at less favorable conclusions, possibly attributed to the multifaceted nature of depression and the diverse approaches to fortifying lactobacilli.19
Of significance, a study comparing the effects of two distinct prebiotics (fructooligosaccharides and galactooligosaccharides) on mood-related improvements unveiled a shift in emotional bias favoring positive words and a reduction in salivary cortisol compared to placebo.14 Similarly, reseachers have noted that while synbiotic supplementation designed to enhance bifidobacteria and lactobacilli did not distinctly diminish depression and anxiety, it did demonstrate improvements in cognitive reactivity during sadness, notably in terms of rumination.20
Recognizing the interplay between treatment methods, another study in 2021 highlighted the possibility that certain selective SSRIs could have antimicrobial properties, potentially disturbing the balance of microbes. It is important to note that using SSRIs can result in side effects like gastrointestinal problems, including constipation, diarrhea, and nausea.21 Essentially, the medications employed to manage depression can inadvertently impact the gut microbiome’s health, thereby exacerbating the disorder’s risk and severity. To counteract this, the researchers propose that concurrently replenishing diverse strains of bacteria through probiotic supplementation and consumption of cultured-rich foods could enhance the treatment effects of SSRIs and mitigate their potential detriment to the gut microbiome.21
The connection between the gut microbiome and its potential implications on depression presents a fascinating and multifaceted realm of exploration that has captured the attention of researchers, healthcare professionals, and the public. As the understanding of the gut-brain connection deepens, mental health therapists find themselves at the forefront of a burgeoning field that offers novel insights into the etiology, progression, and potential treatment avenues for depression. For mental health therapists engaging with clients wrestling with depression and showing an interest in exploring the intriguing possibility of the gut microbiome’s influence, a set of recommendations is proposed to guide their approach and practice.
The starting point for mental health providers exploring the complex world of the gut microbiome and depression is to cultivate a holistic understanding of the interconnection between these two seemingly distinct realms. This involves recognizing the bidirectional communication pathways through which the gut microbiome influences brain function and emotional well-being. Building this foundational knowledge equips therapists to approach their clients’ concerns comprehensively, facilitating more informed discussions and interventions.22
Every individual’s journey with depression is unique, and when the potential influence of the gut microbiome is added to the equation, the complexity further deepens. Mental health therapists are encouraged to adopt a client-centered and collaborative approach, valuing the client’s perspective, concerns, and goals. Collaborative discussions can help clients feel empowered to explore the potential role of their gut health in their mental well-being and allow therapists to tailor interventions that align with the client’s needs and preferences.
A comprehensive assessment that extends beyond the traditional mental health history is essential when exploring the gut microbiome’s potential influence on depression. In addition to the client’s emotional and psychological history, therapists should inquire about digestive issues, dietary habits, medication usage, and any existing health conditions. This holistic assessment informs a tailored treatment approach considering the client’s overall health.
Given the complexity of the gut microbiome and its potential implications for mental health, therapists are advised to collaborate closely with medical professionals specializing in gut health. Gastroenterologists, nutritionists, and functional medicine practitioners can provide insights into the client’s gut microbiome status, recommend appropriate assessments, and offer guidance on dietary and lifestyle adjustments that might positively impact mental well-being.23
While therapists are not nutrition experts, collaborating with registered dietitians or nutritionists can be invaluable in guiding clients toward dietary modifications that support gut health. Encouraging a balanced diet rich in fiber, probiotics, prebiotics, and fermented foods can contribute to a thriving gut microbiome, potentially impacting mood and well-being.24
Mindfulness can extend beyond emotional regulation and stress reduction to encompass mindful eating. Mental health therapists can introduce mindfulness techniques around eating, encouraging clients to savor their meals, cultivating awareness of hunger and fullness cues, and observing how different foods affect their emotional and physical states.25
The ongoing unraveling of the gut microbiome and mental health connection holds the promise of pioneering therapeutic avenues for therapists engaging with clients exploring the gut microbiome’s impact on depression; collaboration with medical professionals, holistic assessments, education, and tailored interventions are pivotal. A balanced approach, including nutrition, mindfulness, and open-minded engagement, can empower clients to make informed decisions about their well-being.
Understanding the connection between the gut microbiome and depression has significant implications for public health strategies, especially in its potential impact on mental health, specifically depression. As the scientific community continues to explore the therapeutic potential of modulating the gut microbiome for depression management, mental health professionals have an essential role to play. Recommendations for therapists engaging with clients experiencing depression linked to the gut microbiome include collaboration with medical professionals specializing in gut health, holistic assessments that consider physical and mental health history, education to empower clients with knowledge about the gut-brain connection, and guidance on nutrition, mindfulness, physical activity, and tracking their well-being. A client-centered approach, characterized by tailored interventions and realistic expectations, will be vital in navigating this evolving field.
In conclusion, the increasing recognition of the gut microbiome’s impact on depression can transform the mental healthcare landscape. This relationship opens new avenues for understanding and treating depression while underscoring the need for collaborative and holistic approaches in providing comprehensive care to individuals whose mental health is intertwined with their gut microbiome. As science unfolds, mental health professionals stand poised to bridge the gap between research and practice, ultimately enhancing the well-being of their clients.
We declare that none of the authors have any personal, commercial, or financial interests that could influence or bias the research findings and opinions presented in this manuscript.
Peter Gordon, MS, is a Mental Health Clinician and Graduate Student in the Clinical Psychology (PsyD) program at George Washington University
James Maiden, Ed.D, LPC, NCC, is the Assistant Dean for Student Affairs at Uniformed Services of the Health Sciences
Delarious O. Stewart, Ed.D, LPC-S, ACS, NCC, NCSP, NCSC, is an Assistant Professor and Director of the School Counseling program at the University of the District of Columbia
Phronie Jackson, Ph.D., is an Assistant Professor and Director of the Health Education program at the University of the District of Columbia