According to the World Health Organization, 1 in 8 people worldwide suffer from mental disorders. Conditions like depression, stress, and anxiety are becoming increasingly common, a trend that has been exacerbated by the rise of social media and the recent COVID-19 pandemic. However, other factors also play a significant role, and they might be closer than you think – nestled right within our gut.
The microbiota-mental health connection
The human gut microbiota is a complex ecosystem of trillions of microorganisms that live in our digestive system and actively contribute to our overall health. Recent research has also revealed a specific connection between gut microbiota and mental health. Research has shown that individuals diagnosed with mental disorders, such as depression and eating disorders, often have an imbalance in their gut microbiota.
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This imbalance can influence our brain and behaviour through various pathways, including the nervous and endocrine systems. But here’s the catch – our microbiota is as unique as our fingerprint and can change over time due to factors like diet and lifestyle. This makes pinpointing the specific microbes contributing to these disorders a significant challenge.
Why twinning is winning!
Twins provide a unique opportunity to study the interaction between gut microbes and mental health as they share genetic backgrounds, early-life events, and other factors such as dietary patterns and geographical locations. Identical twins share almost all their genetic material, whereas non-identical (or fraternal) twins share about half, similar to non-twin siblings. This allows researchers to tease apart the effect of genetics and environment on the gut microbiota since differences in gut bacteria between identical twins are likely caused by non-genetic factors. In contrast, for non-identical twins, differences could be due to genetic and environmental effects.
Pyramid-layer design
In this study, researchers examined the microbiomes found in stool samples and metabolites circulating in twins’ blood with, without, or at risk of developing a mental disorder for 438 individuals (219 twin pairs). Depression, anxiety, and eating disorders were all considered mental disorders. They adopted a unique pyramid-layer study design where the number of twins investigated increased with the heterogeneity of the population.
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At the top of the pyramid, twins were compared, where one twin suffered from a mental disorder while the other did not. In the first layer, they examined identical twins; in the second layer, non-identical twins were examined; and in the third layer, all twins were combined. At the pyramid base, their findings were verified for non-shared environmental factors: age, gender, BMI, antibiotics usage of the prior month, and vegetable and fruit intake.
Here, the healthy counterpart of a twin diagnosed with a mental disorder was considered at risk of developing a mental disorder. This population was examined in relation to any twin diagnosed with a mental disorder. Lastly, the population of all healthy twins was compared to the population of twins diagnosed with a mental disorder.
The link between gut microbiota and mental disorders
Overall, the researchers found a higher similarity in the microbiomes and plasma metabolome composition in identical twins than in non-identical twins. This suggests that both genetic and environmental factors shape the gut microbiota. In addition, they found some interesting links with mental disorders:
1. Parabacteroides: A key player in mental disorder
The bacterial genus Parabacteroides emerged as the most strongly associated with mental disorders across all layers of the pyramid study design. However, previous reports hint at the health-promoting effects of these bacteria through the production of short-chain fatty acids, suggesting that their elevating might be a compensatory mechanism in mental disorders. Parabacteroides species have also been linked to neurotransmitters and metabolites, of which dysfunctions in their signalling pathways are related to depression and anxiety. In addition, a positive correlation was found between the abundance of Parabacteroides and the signalling pathway that regulates our sugar level in the blood. Further investigation is required to elucidate the exact role of this bacteria in depressive, stress, and anxiety-like behaviours.
2. The intricate interplay between gut microbiota and mental well-being
The researcher identified several other microbiota species associated with mental health in several pyramid layers, but not all of them. Decreased abundances of certain genera (like Ruminococcaceae UCG 013, Lachnospiraceae UCG 008, and Lachnospiraceae UCG 006) and increased abundances of other genera (like Ruminococcaceae UCG 014, Family XIII AD3011 group, and unclassified Christensenellaceae) were linked to mental disorders. The researcher suggests combining multiple omics techniques (such as transcriptomics, proteomics, and metabolomics) to get more comprehensive insights into the functionally related microbial communities of the gut microbiota rather than single-microbe abundance better to understand their interactions and influence on our mental health.
3. Are vitamins involved?
In the study, the vitamin A and C metabolic pathways were more active in the gut microbiota of twins with a mental disorder than healthy controls. However, these results were insignificant when corrected for individual-level confounders (age, gender, BMI, antibiotics usage of the prior month, and vegetable and fruit intake). Therefore, personal levels of vitamin metabolism and personal dynamics of the gut microbiome should be considered to further explore the involvement in mental disorders.
Take-home message
The gut microbiota is a complex and fascinating ecosystem. Its influence reaches beyond digestion, shaping our health and mental well-being in ways we only begin to understand.
The study findings indicate that the pyramid-layer design for twin studies provides a robust method for identifying factors in diseases that have both genetic and environmental contributions. These factors can be further examined to understand their role in mental disorders. For instance, current findings suggest that a high abundance of Parabacteroides could be a symptom of mental disorders and could potentially serve as a new biomarker. This discovery opens up new opportunities for determining a person’s risk of developing mental disorders. Furthermore, understanding the pathways related to our mental well-being could contribute to the development of new treatments that target gut microbiota to overcome mental disorders.
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Journal reference
Delanote, J., Correa Rojo, A., Wells, P. M., Steves, C. J., & Ertaylan, G. (2024). Systematic identification of the role of gut microbiota in mental disorders: a TwinsUK cohort study. Scientific Reports, 14(1), 3626. https://doi.org/10.1038/s41598-024-53929-w
