Twin study investigates the role of the microbiome as a modifier in mental disorders

By Dr. Chinta SidharthanFeb 15 2024Reviewed by Danielle Ellis, B.Sc.

In a recent study published in the journal Nature Scientific Reports, researchers examined whether the influence of gut microbiome perturbations on various biological processes, such as the dysregulation of the hypothalamic–pituitary–adrenal axis, performance of the immune system, and the production of neurotransmitters and short-chain fatty acids contributed to the manifestation and progression of mental health disorders such as anxiety, depression, and eating disorders.

Gut microbiota and the brain

The discovery of the gut microbiome and its vital role in human health has resulted in a surge of studies examining the role of gut microbiome dysbiosis in various physical and mental health diseases. Recent studies have reported that dysbiosis of the gut microbiome is present in a significant number of patients with mental health disorders such as anxiety, depression, and eating disorders.

While imbalances among some microbiota can have an impact on the neuronal and humoral mechanisms in the brain, affecting the vagus nerve, gut microflora can also modify the blood-brain barrier and affect the endocrine pathways. Furthermore, gut microbiome metabolites such as amino acids, short-chain fatty acids, and secondary bile acids can influence brain functions such as memory, behavior, and learning.

However, the gut microbiome is dynamic and specific to each individual. Furthermore, while the maternal microbiome initially shapes the composition of the gut microbiome of the infant, factors such as diet, lifestyle, medication, and physiological factors are responsible for the composition of the adult microbiome. Additionally, various genetic and environmental factors are also known to influence the development and progression of neuropsychiatric disorders, making the identification of the role of the gut microbiome in mental health disorders very complicated.

About the study

In the present study, the researchers used the twin registry in the United Kingdom (UK) to screen dizygotic and monozygotic twins who were discordant for mental health disorders to study the differences in the abundance of gut bacterial genera and the levels of circulating metabolites to understand the role of the gut microbiome in mental health diseases.

Dizygotic twins result from two eggs being fertilized by two sperms during the same pregnancy and, therefore, similar to non-twin siblings, share half their genetic material. Monozygotic twins are conceived when one fertilized egg splits into two and forms two fetuses, making them genetically identical.

Co-twin studies allow the interpersonal variations to be studied while accounting for the confounding factors since twins share vital factors such as genetic background and life factors such as mode of birth, early nutrition, and geography. Furthermore, the comparisons between monozygotic and dizygotic twins can help understand the extent to which genetics contribute to the disease.

Mental health disorders are known to have variable levels of heritability, with depression having a 35% to 45% heritability while anxiety being 35 % to 50% heritable. Eating disorders such as binge eating, bulimia nervosa, and anorexia nervosa are 39%– 45%, 60%, and 28%–74% heritable, respectively, according to previous studies.

The present study aimed to use longitudinal data from the UK Adult Twin Registry to characterize the gut microbiota and plasma metabolomes and decipher bacterial genera, microbial pathways, and plasma metabolites that could impact the development or progression of mental health disorders in monozygotic and dizygotic twins, including potential gut microbiome differences between both types of twins.

Major findings

The results showed that the abundance of the bacterial genus Parabacteroides was associated with mental health disorder diagnoses. Furthermore, the abundance of eight other bacterial genera, including Dorea, Victivallis, Mollicutes, Pseudoflavonifractor, and Ruminococcaceae, were found to be different between the monozygotic twin with mental health disorders and the healthy twin.

Additionally, subfractions of high-density lipoprotein such as extra-large high-density lipoprotein free cholesterol, high-density lipoprotein 2 cholesterol, large high-density lipoprotein particles, valine, large high-density lipoprotein lipids, large high-density lipoprotein cholesterol, and large high-density lipoprotein esterified cholesterol were also found to have different abundance between monozygotic twins with mental health disorders and healthy co-twins.

Analyses in dizygotic twins showed two bacterial genera — Family XIII AD3011 group and Ruminococcaceae UCG 013 to have similar abundance dissimilarities between twins with mental health disorders and their healthy co-twins as the study among monozygotic twins. However, the metabolites identified to be different between the twins with mental health disorders as compared to the healthy twin in the dizygotic twin pairs were not the same as those identified in the monozygotic pairs.

Previous studies have also found an increased abundance of the genus Parabacteroides associated with major depressive disorder. However, the genus is believed to play a health-promoting role in the production of short-chain fatty acids, indole, and γ-aminobutyric acid or GABA. Dysfunctions in signaling pathways involving these molecules have been linked to anxiety and depression, suggesting that the increased abundance of Parabacteroides associated with mental health disorders could be a possible compensatory mechanism.