Abstract

The current review investigates the impact of whole dietary changes and the microbiome-gut-brain axis on depression and anxiety. Mental ill-health is a rapidly growing global issue, with depression and anxiety representing the most common mental illnesses. Despite decades of research, there has been a marked failure in adequately addressing this mental health crisis. This review assesses whether whole dietary interventions offer a potential solution for depression and anxiety.

Findings showed that the Mediterranean and Japanese diets were associated with reductions in depression, though there was less evidence available for anxiety, highlighting an overall need for further randomised controlled trials to establish causal links.

Broadly, dysbiosis in the gut microbiome was associated with an increased risk of depression and anxiety. However, there is a lack of human-based randomised controlled trial data investigating the gut microbiome in relation to mental health.

Despite promising preliminary research, there is an overall lack of consensus in the literature on dietary interventions for depression and anxiety. At present, whole dietary interventions implementing the Mediterranean diet show the greatest potential, though there is a lack of understanding regarding the potential underlying mechanisms related to the microbiome-gut-brain axis.

Keywords: Depression, Anxiety, Mental Health, Nutrition, Diet, Gut-Brain Axis, Gut Microbiome 

Introduction

Optimal nutrition is crucial for overall health and well-being (Adan et al., 2019). Dietary guidelines differ geographically but almost unanimously emphasise the importance of lowering red meat and processed food intake while increasing whole grain, vegetable, and fruit intake (Ventriglio et al., 2021). For decades, research has investigated the role of dietary intake in disease progression and development. Key associations have emerged over the years despite ongoing debates about the causality and strength of these associations (Noce et al., 2021).

Despite numerous debates in the field of nutrition and health, there is clear epidemiological data associating the modern Western diet with increased disease risk, including but not limited to obesity and metabolic syndromes. Conversely, diets higher in fibre and lower in processed meat intake are consistently associated with a lower risk of disease and increased longevity (Monteiro et al., 2013).

Due to the strong association between specific dietary patterns and physical health, researchers have become increasingly interested in the potential role that dietary intake may have in relation to mental health. Worldwide, mental health issues, specifically depression and anxiety, have become leading causes of disability. An estimated 3.8% of the population experiences depression and 4% experiences anxiety (World Health Organization, 2017). These conditions are influenced by biological, social, and psychological factors such as financial conditions, social standards, pre-existing medical conditions, and other stressful life events (Ryu and Fan, 2022).

Depressive disorder is a common mental disorder characterised by a depressed mood or loss of pleasure or interest in activities for extended periods (World Health Organization, 2023). Depression lowers patients’ qualities of life, is associated with reduced longevity, and increases disease risk (Gurung and Shristy, 2023; Clarke and Currie, 2009). Depression has significantly increased by 6.9% from 2015 to 2020, particularly among people aged 18 to 25. In 2020, researchers found that 1 in 10 Americans and almost 1 in 5 adolescents and young adults had experienced depression for longer than a year (Koskie, 2023). Ongoing studies continue to improve our understanding of the biological, psychological, and social factors of depression.

Anxiety disorders are among the world’s most common mental disorders, affecting an estimated 301 million people in 2019 (World Health Organization, 2023). Symptoms disrupt daily activities such as job performance, schoolwork, and relationships. Clinical anxiety can cause difficulty in daily activities, socialising, and participating in new activities. Chronic anxiety can exacerbate cardiovascular issues, contributing to higher risks of hypertension and heart disease (Thurston, Rewak, and Kubzansky, 2013). Furthermore, anxiety has been linked to compromised immune function, potentially increasing susceptibility to infections (Arranz et al.,2007). Anxiety significantly reduces quality of life (Bazely, 2024). Similar to depression, anxiety causes physiological symptoms such as increased heart rate, palpitations, shortness of breath, rapid breathing, and chest pain or pressure (Chand and Marwaha, 2023).

Despite the availability of antidepressants and therapy, treatment presents major challenges (Popa-Velea et al., 2015). Antidepressants, which help many people with depression and anxiety by modifying neurotransmitter levels, have adverse effects and vary in potency. Therapy treats psychological issues but faces challenges such as limited availability and stigma (Rush et al., 2022). Geographical variations in access and wait times hinder treatment, especially in low-resource countries. Anxiety and depression frequently coexist, with similar treatment techniques but distinct symptomatology. Comorbidity rates are estimated at 46% to 75% (Luo et al., 2024).

The current global mental health crisis highlights the limitations of traditional therapy and mental health services in meeting widespread demand. Despite tremendous efforts, many people still lack access to adequate healthcare (National Council for Mental Wellbeing, 2024). Considering this need, research into alternative evidence-based therapeutic interventions, such as diet, becomes critical.

Existing literature provides insight into relevant dietary patterns and nutrients tied to depression and anxiety levels. Research has linked increased consumption of “Western” style diets high in processed foods, sugar, sodium, and saturated fat to worse symptoms (Jacka et al., 2010; 2017). These dietary patterns are proposed to influence neurotransmitter systems in the brain (Gao et al., 2020; Rucklidge and Kaplan, 2013). In contrast, certain nutrients obtained through whole foods may have antidepressant and anxiolytic effects. Research has also associated increased Omega-3 fatty acid intake with reduced symptoms of depression and anxiety through proposed neuroprotective properties and anti-inflammatory effects (Kiecolt-Glaser et al., 2015).

Additionally, emerging research draws connections between the gut-brain axis and mental health. Diet heavily influences gut microbiota composition, and gut microbial dysbiosis is hypothesised to impact neurotransmitter signalling, immune function, and the HPA axis stress response (Kelly et al., 2016). Such biological mechanisms offer potential explanations for nutritional influences on depression and anxiety.

The current evidence on the impact of nutrition on depression and anxiety is unclear, as there have been few randomised controlled trials assessing the health effects of specific diets and nutrients on these conditions. Additionally, current evidence regarding the biological mechanisms of action in relation to the gut-brain axis are unclear (Firth et al., 2020; Kris-Etherton et al., 2020).

Nutrition’s role in physical health is well understood, as micro and macronutrients provide energy to cells, support immune cells to fight off infections, and promote repair, which are essential for improving physical performance and longevity (Koehler and Drenowatz, 2019; ELS, 2024). However, there is a dearth of literature addressing the potential role of nutrition in depression and anxiety disorders. Researchers have identified individual nutrients as being protective of mental health and associated with reductions in depression and anxiety, including Omega-3 PUFA (Kris-Etherton et al., 2020). Despite growing attention, there remain inconsistencies in the current data and few high-quality, statistically powered randomised controlled trials addressing the impact of whole dietary changes on depression and anxiety.

As a result, this review aims to summarise the current knowledge on nutritional interventions in the prevention and treatment of depression and anxiety, which are the most prevalent mental health disorders worldwide and are rising in rates globally (Moitra et al., 2023; Santomauro et al., 2021). This review will also investigate the potential relationship between whole dietary changes and the microbiome-gut-brain axis in relation to symptoms of depression and anxiety.

The impact of whole dietary changes on depression and anxiety

The Mediterranean diet is inspired by the traditional eating habits of countries bordering the Mediterranean Sea. It emphasises a variety of fruits, vegetables, whole grains, nuts, seeds, olive oil, and moderate amounts of fish, chicken, and dairy. Extensive research has shown that this diet improves cardiovascular health (Estruch et al., 2018). These benefits are attributed to the diet’s high content of monounsaturated fats, fibre, and antioxidants, which contribute to reduced inflammation and improved lipid profiles.

In recent years, attention has shifted to the Mediterranean diet’s potential impact on mental health, particularly concerning depression and anxiety. The SMILES trial (Jacka, 2017), a 12-week randomised controlled trial, demonstrated that adopting a Mediterranean diet could significantly reduce depression symptoms over a 12-week period. The underlying mechanisms for these effects are not entirely clear, but potential factors include reduced inflammation, improved micronutrient intake, and support for a healthy gut microbiome.

Cross-sectional studies have also supported the association between Mediterranean diet adherence and improved mental health outcomes. For instance, research indicates that individuals following this diet tend to report lower levels of depression and anxiety (Sánchez-Villegas et al., 2015). However, these studies are unable to provide any causal inference. More robust evidence comes from randomised controlled trials, which offer stronger support for the diet’s efficacy. The HELFIMED trial found that a Mediterranean diet, particularly one incorporating olive oil and nuts, was associated with reduced depressive symptoms (Parletta, 2017). Effects notably continued beyond the 12-week intervention up to 6 months. However, the PREDIMED trial, a 12-week randomised controlled trial implementing the Mediterranean diet, failed to find significant reductions in depressive symptoms, with only a subset of participants who had type 2 diabetes showing a significant reduction in depressive symptoms (Martínez-González et al., 2015).

Overall, while the research indicates the potential benefits of the Mediterranean diet for treating depression and anxiety, limitations persist. Cross-sectional studies provide valuable associative data but cannot establish causality. Randomised controlled trials offer more reliable evidence but can be limited by factors such as short study durations, variability in adherence, and inconsistent results. Despite these limitations, the cumulative evidence suggests that the Mediterranean diet may be a beneficial intervention for improving mental health, warranting further research to better understand its mechanisms and long-term effects.

The traditional Japanese diet is characterised by a diverse array of nutrient-dense foods, including fish, vegetables, fermented products, and green tea. This diet features a variety of seafood, particularly fatty fish, like salmon, mackerel, and sardines, which are high in Omega-3 fatty acids essential for brain health. Omega-3 fatty acids contribute to brain structure and function by influencing neurotransmitter pathways, which can help reduce the risk of anxiety and depression (Koga, 2019). The diet also incorporates soy products such as tofu, miso, and natto, which provide high-quality proteins necessary for neurotransmitter synthesis and mood stability (Mansoor, 2022).

Japanese meals are rich in vegetables, offering a variety of vitamins, minerals, and antioxidants like vitamin C and beta-carotene. These nutrients are important for reducing oxidative stress and maintaining overall brain health. Additionally, green tea, a staple in the Japanese diet, is high in L-theanine, an amino acid that promotes relaxation without causing drowsiness, thus supporting a calm and focused mental state (Shimbo, 2005).

Research into the health benefits of the Japanese diet has primarily focused on its physical health advantages. Studies have demonstrated that the diet’s high Omega-3 content and antioxidant-rich vegetables contribute to lower rates of cardiovascular diseases (Tada et al., 2011). However, the potential mental health benefits are also notable. Cross-sectional studies have shown associations between adherence to the Japanese diet and lower levels of depression and anxiety (Konishi, 2020). While these studies provide valuable insights, they are limited by their observational nature, which establishes associative rather than causal relationships. Further evidence comes from randomised controlled trials which offer stronger support for dietary interventions. For example, randomised controlled trials have confirmed that Omega-3 supplementation can independently improve symptoms of depression (Grosso et al., 2014). While direct studies on the Japanese diet are less common, the beneficial effects of its components have been well-documented.

The strengths of the existing research include the clear links between specific dietary components and mental health outcomes, supported by both observational and experimental studies. However, limitations persist. Observational studies provide associative data, which do not establish causality, and randomised controlled trials on the Japanese diet specifically are limited. Additionally, many studies focus on individual components of the diet rather than the holistic dietary pattern, which may not fully capture the comprehensive impact on mental health.

The Japanese diet contrasts sharply with the Western diet, which is often high in processed foods, saturated fats, and sugars. The Western diet is linked to higher rates of obesity, cardiovascular diseases, and mental health issues, underscoring the potential advantages of the Japanese dietary pattern. However, direct comparisons are challenging due to the variability in dietary practices and health outcomes across populations. While there is promising evidence supporting the health benefits of the Japanese diet, particularly in reducing depression and anxiety, the evidence is not yet robust enough to make definitive public health recommendations. Further research, particularly well-designed randomised controlled trials focusing on the holistic Japanese diet, is needed to confirm its efficacy and inform public health strategies. The current evidence suggests that adopting dietary patterns similar to the Japanese diet could be beneficial, but more targeted research is essential to establish more conclusive recommendations.

The vegan diet, characterised by the consumption of whole grains, legumes, fruits, vegetables, nuts, and seeds, offers a range of physical and mental health benefits. This diet is rich in fibre and essential nutrients, which contribute to overall health and can positively impact mental well-being (Mokhtari et al., 2022). Research indicates that a vegan diet can reduce the risk of chronic diseases such as heart disease, type-2 diabetes, and hypertension, largely due to its low levels of saturated fat and high nutrient density. Studies have found that plant-based diets are associated with lower blood pressure and cholesterol levels, which can decrease cardiovascular risk (Tuso et al., 2013). Additionally, evidence suggests that vegan diets may be linked to increased longevity, showing lower mortality rates among vegans compared to non-vegans (Key et al., 2014). Veganism is practised by a small but growing segment of the population. An estimated 79 million people worldwide are vegan (Vegan Statistics, 2023).

Despite these benefits, maintaining mental health on a vegan diet requires careful attention to nutrient intake. Essential nutrients such as Omega-3 fatty acids and vitamin B12, which are critical for brain function and mood regulation, are less abundant in plant foods. Omega-3 fatty acids, typically found in fish, can be sourced from plant-based alternatives like walnuts, flaxseeds, chia seeds, and algae-based supplements (Saidaiah et al., 2024). Vitamin B12 is crucial for neurological health, including the maintenance of nerve cells and the synthesis of neurotransmitters. A deficiency in vitamin B12 is associated with neurological symptoms, such as mood disorders and cognitive impairment. Studies have shown that vegans who do not supplement are at slightly higher risk of B12 deficiency, which may increase risk of mental health issues such as depression (Woo, Kwok, and Celermajer, 2014). 

Psychological factors also play a role in the mental health outcomes of those following a vegan diet. Many individuals choose veganism due to ethical beliefs about animal welfare and environmental sustainability. This alignment with personal values can enhance mental well-being by providing a sense of purpose and coherence (Beezhold, 2015). However, social challenges, such as limited vegan options or unsupportive peers, can affect mental health.

The high fibre content of vegan diets supports a healthy gut microbiome, which may contribute to mental health benefits. Fibre promotes the growth of beneficial gut bacteria, which can positively influence mood and cognitive function. A healthy gut microbiome is associated with reduced inflammation and better mental health outcomes, as indicated by research on the relationship between gut health and mental well-being (Neufeld et al., 2013). Thus, the fibre-rich nature of vegan diets could play a protective role in mental health through its impact on gut health though high-quality randomised controlled trials assessing this are lacking.

In summary, the vegan diet presents potential benefits for both physical and mental health, though it requires careful management to ensure nutritional adequacy. The evidence supports its advantages in chronic disease prevention and longevity and suggests possible mental health benefits related to dietary factors and psychological satisfaction. However, further research is needed to fully understand the extent of these benefits and to explore the interplay between dietary patterns and mental health outcomes.

Gut microbiota

The gut microbiota, consisting of bacteria, archaea, fungi, and viruses, plays a crucial role in health and disease. The dominant phyla in the gut microbiota are Firmicutes and Bacteroidetes, which together constitute about 90% of the bacterial population (Rinninella et al., 2019). The composition of the gut microbiome can vary based on age, gender, geographical location, disease, and diet (Mörkl et al., 2018). The gut-brain axis, a bidirectional communication system between the central nervous system and the enteric nervous system, is a key pathway through which the gut microbiota may influence mental health (Cryan et al., 2019).

Dysbiosis, an imbalance in the gut microbiota, is associated with various mental disorders, including depression and anxiety. Dysbiosis can manifest as a loss of beneficial microorganisms, an overgrowth of harmful microorganisms, and a reduction in microbial diversity (Dinan & Cryan, 2017). Studies have shown that individuals with anxiety and depression often exhibit altered gut microbiota profiles. For example, there is often an increase in bacteria such as Bacteroides and a decrease in bacteria such as Firmicutes and Faecalibacterium in these individuals (Zheng et al., 2016).

Short-chain fatty acids (SCFAs) produced by gut bacteria, such as butyrate from Firmicutes, play a critical role in maintaining gut health and integrity. SCFAs have been linked to anti-inflammatory effects and improved blood-brain barrier function, potentially influencing brain health and behaviour (Dalile et al., 2019). Animal studies have shown that gut microbiota from depressed patients can induce depressive-like behaviour in germ-free mice, suggesting a causal role of the microbiota composition in depression (Kelly et al., 2016).

Gut microbial dysbiosis has been associated with increased intestinal permeability, commonly referred to as “leaky gut,” which can lead to systemic inflammation and affect the brain through the hypothalamic-pituitary-adrenal (HPA) axis (Maes et al., 2012). This pathway may contribute to the development of anxiety and depressive symptoms (Foster and McVey Neufeld, 2013). However, while these findings are supported by animal studies, further research is needed to confirm these mechanisms in humans.

Research indicates that individuals with depression often have a lower abundance of anti-inflammatory bacteria such as Faecalibacterium and an increased abundance of pro-inflammatory bacteria such as Alistipes (Jiang et al., 2015). This microbial imbalance may contribute to the chronic low-grade inflammation observed in depression (Foster et al., 2021).

Neurotransmitters

Research has demonstrated that alterations in the gut microbiota can influence the production of various neurotransmitters, which are implicated in a range of mental health disorders (Chen et al., 2021). For example, certain strains of Bifidobacteria, such as B. adolescentis, have been shown to promote the production of gamma-aminobutyric acid (GABA), a primary inhibitory neurotransmitter in the brain associated with reduced anxiety (Yang et al., 2023).

Tryptophan, an essential amino acid obtained from protein-rich foods, plays a critical role in neurotransmitter synthesis (O’Mahony et al., 2015). Once absorbed, tryptophan can cross the blood-brain barrier (BBB) via large neutral amino acid transporters and is converted into serotonin in the central nervous system (O’Mahony et al., 2015). It is important to note that approximately 95% of the body’s serotonin is found in the gut, where it is synthesised from tryptophan by enterochromaffin cells (ECs). Serotonin produced in the gut does not readily cross the BBB (Margoob and Kouser, 2024). This has led to debate regarding whether gut-derived serotonin significantly affects mental health through the gut-brain axis, specifically in relation to depression and anxiety.

Animal studies have provided some insights into the relationship between gut microbiota and behaviour. For instance, a study in dogs found that aggressive behaviour, which can be related to anxiety, was associated with changes in the gut microbiota. Specifically, there was a reduction in Bacteroides and an increase in Firmicutes. Since Bacteroides are involved in tryptophan metabolism, a reduction in these bacteria was linked to lower tryptophan and serotonin levels (Homer et al., 2023). While these findings offer preliminary evidence for these mechanisms, there is a need for more research to confirm these results in human populations.

The role of fibre in diet and how it may impact depression and anxiety

Research has broadly associated vegan, Mediterranean, and high-fibre diets with positive mental health outcomes. In contrast, high-protein and high-fat diets have been linked to negative effects on gut microbiota and mental health (Lao et al., 2023). Fibre is thought to influence mental health because it remains undigested until it reaches the large intestine, where it serves as an energy source for the gut microbiota. This process increases microbiota diversity, promotes the growth of beneficial gut bacteria, and enhances the production of SCFAs (Lao et al., 2023).

Higher fibre intake has been shown to increase levels of beneficial gut bacteria strains, such as Bifidobacteria and Lactobacillus, which contribute to the production of SCFAs. These SCFAs, including acetate, propionate, and butyrate, have been associated with improved gut microbial diversity and anti-inflammatory effects (Lao et al., 2023). For instance, Bacteroides predominantly produce acetate and propionate, while Firmicutes are involved in butyrate production (Swann et al., 2019). Increased SCFA production can decrease gut permeability; a condition known as leaky gut, which is associated with depression. Elevated gut permeability allows bacterial toxins to enter the bloodstream, potentially triggering inflammation in the brain (Lao et al., 2023).

Additionally, fibre acts as a fuel source for colonocytes, with butyrate being the primary energy source for these cells (Thomson et al., 2021). Colonocytes are essential for maintaining gut health by regulating the bacterial environment in the colon (Litvak et al., 2018).

Short-chain fatty acids and depression and anxiety

SCFAs are fatty acids containing fewer than six carbon atoms and are primary metabolites produced in the colon by gut bacteria fermenting dietary fibres and resistant starches (Silva, Bernardi, and Frozza, 2020). The three most common SCFAs are acetate, propionate, and butyrate, with typical proportions being approximately 60:20:20 (Silva, Bernardi, and Frozza, 2020). SCFAs support gut health by maintaining the intestinal barrier, promoting mucus production, and protecting against inflammation, which can reduce the risk of colorectal cancer (Silva, Bernardi, and Frozza, 2020). Clinical evidence indicates that faecal SCFA concentrations are lower in individuals with depression compared to those without (Silva, Bernardi, and Frozza, 2020). Additionally, animal studies have demonstrated anti-depressive effects of SCFAs; for example, butyrate supplementation has been shown to enhance memory and promote brain cell growth (Yang et al., 2023). SCFAs can cross the blood-brain barrier (BBB), with studies showing that germ-free mice with increased BBB permeability experienced significant improvements when supplemented with SCFA-producing bacterial strains such as Clostridium tyrobutyricum, resulting in decreased BBB permeability (Braniste et al., 2014). Propionate, in particular, has been shown to protect BBB cells from harmful substances (Silva, Bernardi, and Frozza, 2020).

While substantial animal research supports the positive effects of SCFAs, human studies are limited due to methodological and ethical challenges. Consequently, the effects of SCFAs on the human brain and mental health may differ due to variations in biological mechanisms, and establishing a dose-response relationship remains challenging.

SCFAs also influence neurotransmitter levels; for instance, acetate affects neurotransmitters such as glutamate, glutamine, and GABA in the hypothalamus. Butyrate and propionate impact intercellular potassium levels, which influence cell signalling systems. Furthermore, SCFAs regulate tryptophan 5-hydroxylase 1, an enzyme involved in serotonin synthesis, as well as tyrosine hydroxylase, which is involved in the biosynthesis of dopamine and adrenaline (Silva, Bernardi, and Frozza, 2020).

There is clear associative data linking dysbiosis with an increased risk of mental health disorders, particularly depression and anxiety. The role of SCFAs is of particular interest given their ability to cross the BBB, yet human research remains limited, with an overreliance on animal models. Further randomised controlled trials in humans are needed to explore the biological mechanisms related to the microbiome-gut-brain axis and to assess the impact of whole dietary changes on depression, anxiety, and the gut-brain axis.

CONCLUSION

This review has examined the impact of whole dietary changes on symptoms of depression and anxiety, as well as the potential role of the microbiome-gut-brain axis. It underscores the promising role of nutritional interventions as adjunctive treatments for depression and anxiety. The urgent need to address the escalating global mental health crisis highlights the significance of this review, which aims to improve our understanding of the most effective nutritional strategies for the prevention and treatment of depression and anxiety.

Current research suggests that whole dietary changes, particularly the adoption of the Mediterranean diet, show the most substantial effects in reducing depression and anxiety. While associative data link the traditional Japanese and vegan diets with improved mental health, there is a notable lack of high-quality randomised controlled trials (RCTs) providing causal evidence.

The gut-brain axis (GBA) is proposed as a mechanism through which dietary changes exert their effects; however, there is a significant gap in human data addressing the biological mechanisms involved. Interventional studies have associated dietary patterns high in fibre and low in processed foods — such as the Mediterranean diet — with improved mental health and increased gut microbiome diversity. Potential pathways within the GBA include enhanced production of short-chain fatty acids (SCFAs) like butyrate, though high-quality RCT data are still lacking.

Given the current state of the literature, it is evident that future research should prioritise the replication of existing high-quality RCTs on whole dietary changes. These studies should investigate various biological mechanisms by collecting both stool and blood samples. Preliminary research highlights the potential importance of SCFAs, thus particular attention should be given to the impact of dietary changes on SCFAs in relation to depression and anxiety. Additionally, there is a need for more data from geographically diverse samples, as individual variations in the gut microbiome and differing food landscapes should be considered. Future research should focus on recruiting diverse, statistically powered samples to better understand these variations.

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