The role of the microbiota-gut-brain axis in brain development and mental health

Anxiety disorders are debilitating conditions that carry enormous individual, social and economic costs. For example, it has been estimated that lifelong persistent mental health problems cost the UK taxpayer £8.6 billion annually. Many mental health problems have their onset in the transitional period from adolescence to early adulthood, possibly a result of the complex and concurrent hormonal, genetic, brain maturational and social changes during this period. Research has shown that brain development and maturation extends well into the third decade of life and that brain activation patterns in late adolescence and early adulthood still differ significantly from mature adults. In the recent years, the microbiome has emerged as a new and important factor that may increase the mental health risk for an individual. The intestine and the brain are intimately connected via the gut-brain axis, which involves bidirectional communication via neural, endocrine and immune pathways. Research in both the human and animal models has also highlighted the important role that intestinal microbiota play in regulating the brain, subsequent behaviour, and particularly in anxiety-like behaviour. Most importantly, it has been shown that the period of adolescence may be a critical window during development where microbiota help fine-tune the gut-brain axis related to stress responses and anxiety.

The research proposed here will investigate the role of the microbiota-gut-brain axis in brain development and mental health. Specifically, the researchers will investigate the effect of prebiotic intake on mental health and well-being in late adolescence/early adulthood, with a particular focus on cortical excitability and connectivity in the emotion regulation brain network.

This research will extend previous research into gut-brain interactions into the final years of adolescence. The period of adolescence is not only important with regards to fine-tuning emotion regulation networks, but also, as has been shown in recent work, critical for establishing healthy gut-brain communication patterns. Specifically, here we will investigate how prebiotic intake (Galacto-oligosaccharides) for 4 weeks affects cognitive functioning, psychological well-being and the underlying brain networks in a sample of 120 female undergraduate students (aged 18-25 years). Specifically, the proposed research has two main aims:

1. To investigate how prebiotic intake affects cortical excitability and plasticity, such as inhibitory GABA/ excitatory glutamate levels in key emotion regulation brain networks.
2. To investigate how prebiotic intake affects psychological functioning and well-being, in particular with regards to anxiety and thought control abilities.

120 participants will be divided into two group of 60 participants, groups will be matched for age, handedness and socio-economic status. At each testing time (Time 1, 2 and 3), participants in both groups will undergo comprehensive behavioural and psychological testing to establish baseline measures of cognitive functioning and psychological well-being (such as anxiety levels).

Each participant will also be asked to collect a stool sample at home for 16s rRNA sequencing of the microbiome at both testing times. Group 1 will receive a daily dosage of GOS over 4 weeks, whereas group 2 will receive a placebo over the same period. In addition, participants from either group will also participate in a brain imaging session to assess the effect of prebiotic supplement intake on the functional responsiveness of emotion regulation brain networks.

For this study, The researchers predict that the intervention group will show improvements in behavioural and psychological variables related to emotion regulation and anxiety in comparison to the placebo group (Hypothesis 1). Predictions also expect to observe decreased excitability in core emotion regulation brain regions such as the amygdala and prefrontal cortex, as assessed via 1H-magnet resonance spectroscopy (Hypothesis 2).

Inclusion Criteria:

• Females
• Aged between 18-25

Exclusion Criteria:

• Clinical levels of anxiety and/ or co-morbid diagnoses (e.g. depression)
• Current or previous neurological disorders
• Current or previous psychiatric disorders
• Current or previous gastrointestinal disorders
• Current or previous endocrine disorders
• Antibiotic use 3 months prior to the study
• Regular use of pre- and probiotics, including 3 months prior to the study
• Vegan diets