The Link Between the Gut Microbiome and Mental Health

31 May 2022by Dana Walsh0

The COVID-19 pandemic has brought increased attention to mental health and its related disorders. Many people have experienced mental health issues in the past two years, either due to pandemic-related life changes or infection with the virus itself. In a scientific brief on its Global Burden of Disease study, the World Health Organization (WHO) estimates that the pandemic has led to a 27.6% increase in cases of major depressive disorder (MDD) and a 25.6% increase in anxiety disorders (AD) worldwide in 2020 (World Health Organization, 2022). In the USA, the 2021 State of Mental Health Report indicated that from January to September 2020, 315,220 people took the organization’s online screening test for anxiety—which was a 93% increase over 2019’s total number of screenings (Reinert et al., 2021). Additionally, during the pandemic, 4 in 10 U.S. adults reported symptoms of anxiety or depressive disorders, which was up from 1/10 who reported these symptoms from January to June 2019. Clearly, the pandemic has been a driving factor in increased mental health issues.

Recent studies show that the gut microbiome plays an important role in the gut-brain axis and, in turn, mental health. One of the major hormones influencing mental health is the neurotransmitter serotonin (Lin et al., 2014). Serotonin plays a range of roles in the body, including influencing mood, and a lack of it may lead to symptoms of depression and anxiety (Serotonin, 2022). More than 90% of serotonin in the body is synthesized in the gut and gut microbiota play important roles in its regulation (Yano et al., 2015). Metabolites produced by gut microbes stimulate host gut enterochromaffin cells to produce serotonin, some of which enters circulation and travels to the brain to participate in the gut-brain axis (Layunta et al., 2021; Yano et al., 2015). The gut-brain axis involves bidirectional communication between the central nervous system and the gut and facilitates the development and function of the immune, metabolic, and nervous systems (Layunta et al., 2021; Morais et al., 2021). Direct evidence of the association between gut-brain communication and the microbiome comes mostly from rodent models, making it difficult to link the human gut microbiome to mental health. However, some recent studies shed light on this topic.

Possible interactions between diet, the gut microbiota, and mental health. From Bear et. al., 2020.

The Flemish Gut Flora Project, a large study of the gut microbiome in 1,054 individuals, examined how microbial community composition correlates with quality of life and depression symptoms (Valles-Colomer et al., 2019). This work found that the bacterial genera Faecalibacterium and Coprococcus, which are consistently correlated with positive health outcomes, are also associated with higher quality of life. When confounding factors were taken into account, depletion of Coprococcus, along with Dialister, was significantly associated with depression. Both Faecalibacterium and Coprococcus produce butyrate, a short chain fatty acid (SCFA) which has known positive effects directly on the gut, such as regulation of glucose metabolism and intestinal barrier integrity (Caspani et al., 2019). Administration of acetate, butyrate, and propionate, the three most abundant SCFAs, as well as sodium butyrate, improved symptoms of depression in mice, suggesting that bacterial SCFAs may play key roles in depression (Caspani et al., 2019). Another study of 5,959 genotyped individuals with matched gut metagenomic data found a possible causal association of Klebsiella and Morganella with depression, and further found increases of Morganella in 181 individuals who later developed depression (Qin et al., 2022). Both of these bacterial genera are gram-negative pathogens that induce inflammation, which may influence mood.

How the gut microbiota influence mood. MAMPs = microbial associate molecular patterns, 5-HT = serotonin, TLR/NLR = receptors that detect bacterial components From Layunta et. al., 2021

Now that we know there are possible microbial links with mental health, how can we put this information to use, especially in the context of the COVID-19 pandemic? An easily modifiable solution is diet. It is well known that diet modulates the gut microbiota, to the point of causing community fluctuations after consumption of a single meal (David et al., 2013). High-fiber foods enrich for beneficial microbes which break fiber down into metabolites such as SCFAs (Makki et al., 2018). Therefore, consumption of a high-fiber diet may enrich beneficial, SCFA-producing bacteria such as Faecalibacterium and Coprococcus and reduce detrimental gram-negative pathogens, such as Klebsiella and Morganella. In fact, both gut microbiota and diet have been linked to depression and anxiety (Bear et al., 2020). Studies directly linking diet to depression are plagued with study design and interpretation difficulties, as well as conflicting results, making it difficult to establish a solid relationship. However, there is direct evidence linking changes in the microbiome to emotional behaviors associated with anxiety and depression, and since the microbiome is directly impacted by diet, this may explain the link between food and mental health (Bear et al., 2020). Certain foods that benefit the microbiome, like omega-3 fatty acids, fiber, magnesium, vitamin D, and fermented foods, are also associated with improved mood. Although it is difficult to discern whether these foods are truly associated with depression, we can see that they directly alter the composition of the microbiome and enrich for beneficial taxa, suggesting that an overall healthy diet, like the Mediterranean diet, may improve depression and anxiety through modulation of the gut microbiome. More research is needed to solidify and fully understand this link, but, in the meantime, it’s always beneficial to start incorporating microbiome-friendly foods and generally improve your diet and, in turn, your overall health.       



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Dana Walsh

Dana Walsh is a microbiome scientist whose career has consisted of a blend of wet bench and computational research. Currently, she is a Microbiome Scientist for CosmosID where she helps clients with custom microbiome analysis and interpretation as well as exploring new tools and methods for microbiome studies. She applies cutting-edge tools to integrate multi-omics data, including taxonomic, functional, meta-transcriptomics and metabolomics data, in order to help clients derive meaning from their results.

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