Dr Nicola Johnstone

Anxiety disorders disproportionally affect females and are frequently comorbid with eating disorders. With the emerging field of nutritional psychiatry, focus has been put on the impact of diet quality in anxiety pathophysiology and gut microbiome underlying mechanisms. While the relationship between diet and anxiety is bidirectional, improving dietary habits could better facilitate the actions of pharmacological and psychological therapies, or prevent their use. A better understanding of how gut bacteria mediate and moderate such relationship could further contribute to develop personalized programs and inform probiotics and prebiotics manufacturing. To date, studies that look simultaneously at diet, the gut microbiome, and anxiety are missing as only pairwise relationships among them have been investigated. Therefore, this study aims at summarizing and integrating the existing knowledge on the dietary effects on anxiety with focus on gut microbiome. Findings on the effects of diet on anxiety are critically summarized and reinterpreted in relation to findings on (i) the effects of diet on the gut microbiome composition, and (ii) the associations between the abundance of certain gut bacteria and anxiety. This novel interpretation suggests a theoretical model where the relationship between diet and anxiety is mediated and/or modulated by the gut microbiome through multiple mechanisms. In parallel, this study critically evaluates methodologies employed in the nutritional field to investigate the effects of diet on anxiety highlighting a lack of systematic operationalization and assessment strategies. Therefore, it ultimately proposes a novel evidence-based approach that can enhance studies validity, reliability, systematicity, and translation to clinical and community settings.

Background. Galacto–oligosaccharides (GOS) are prebiotics linked to gut microbiota modulation and potential gut–brain axis effects on neurochemistry, mental health and cognition. This study evaluated the influence of GOS along the gut–brain axis, integrating assessments of mental health, neurochemistry, gut microbiome composition, cognition, and nutrition in healthy females. Methods. In a randomised, double–blind, placebo–controlled trial, 83 females (17–25 years) received GOS or placebo for 28 days. Assessments occurred at baseline, endline, and 28 days post–supplementation. The primary outcome was trait anxiety, with secondary outcomes including neurochemical measures of GABA and glutamate via 1H–MRS in the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and inferior occipital gyrus (IOG) of the brain, and gut microbiome composition. Tertiary outcomes included social anxiety, depression, emotion behaviour, reaction times, and nutritional intake. Analyses included intention–to–treat, per–protocol, and sensitivity approaches. Results. Trait anxiety did not differ significantly between groups at endline (p = .443), though trends favoured lower anxiety in the GOS group at follow–up (p = .069). GOS reduced GABA at trend significance in the inferior occipital gyrus (p = .053) and dorsolateral prefrontal cortex (p = .088) in high–anxious participants, with effects persisting at follow–up. GOS increased Bifidobacterium abundance (p = .001) but did not affect overall microbiome diversity. Tertiary outcomes showed no significant changes in social anxiety or depression but faster reaction rates in high–anxious participants for simple (p = .036) and choice tasks (p < .001). Nutritional intake was unaffected. Conclusion. While GOS supplementation did not significantly reduce trait anxiety, it produced neurochemical changes and transient modulations of the gut microbiome in Bifidobacterium abundance. These findings suggest GOS induced changes can be traced along the gut–brain axis, with implications for mental health and cognitive function that warrant further investigation.

Between the ages of 10-25 years the maturing brain is sensitive to a multitude of changes, including neurochemical variations in metabolites. Of the different metabolites, gamma-aminobutyric acid (GABA) has long been linked neurobiologically to anxiety symptomology, which begins to manifest in adolescence. To prevent persistent anxiety difficulties into adulthood, we need to understand the maturational trajectories of neurochemicals and how these relate to anxiety levels during this sensitive period. We used magnetic resonance spectroscopy in a sample of younger (aged 10-11) and older (aged 18-25) females to estimate GABA and glutamate levels in brain regions linked to emotion regulation processing, as well as a conceptually distinct control region. Within the Bayesian framework, we found that GABA increased, and glutamate decreased with age, negative associations between anxiety and glutamate and GABA ratios in the dorsolateral prefrontal cortex, and a positive relationship of GABA with anxiety levels. The results support the neural over-inhibition hypothesis of anxiety based on GABAergic activity.

Here we argue that a multidisciplinary research approach, such as currently practised in the field of developmental cognitive neuroscience, is key to maintaining current momentum and to future-proof the field of microbiome-gut-brain research. Moreover, such a comprehensive approach will also bring us closer to our aims of translation and targeted intervention approaches to improve mental health and well-being.

Research has shown that difficulties with emotion regulation abilities in childhood and adolescence increase the risk for developing symptoms of mental disorders, e.g anxiety. We investigated whether functional magnetic resonance imaging (fMRI)-based neurofeedback (NF) can modulate brain networks supporting emotion regulation abilities in adolescent females. We performed three experiments (Experiment 1: N ​= ​18; Experiment 2: N ​= ​30; Experiment 3: N ​= ​20). We first compared different NF implementations regarding their effectiveness of modulating prefrontal cortex (PFC)-amygdala functional connectivity (fc). Further we assessed the effects of fc-NF on neural measures, emotional/metacognitive measures and their associations. Finally, we probed the mechanism underlying fc-NF by examining concentrations of inhibitory and excitatory neurotransmitters. Results showed that NF implementations differentially modulate PFC-amygdala fc. Using the most effective NF implementation we observed important relationships between neural and emotional/metacognitive measures, such as practice-related change in fc was related with change in thought control ability. Further, we found that the relationship between state anxiety prior to the MRI session and the effect of fc-NF was moderated by GABA concentrations in the PFC and anterior cingulate cortex. To conclude, we were able to show that fc-NF can be used in adolescent females to shape neural and emotional/metacognitive measures underlying emotion regulation. We further show that neurotransmitter concentrations moderate fc–NF–effects. •Neurofeedback implementations differentially modulate PFC-amygdala connectivity.•Functional connectivity neurofeedback affect measures of emotion regulation.•Neurotransmitter concentrations moderate neurofeedback effects.

Current research implicates pre- and probiotic supplementation as a potential tool for improving symptomology in physical and mental ailments, which makes it an attractive concept for clinicians and consumers alike. Here we focus on the transitional period of late adolescence and early adulthood during which effective interventions, such as nutritional supplementation to influence the gut microbiota, have the potential to offset health-related costs in later life. We examined multiple indices of mood and well-being in 64 healthy females in a 4-week double blind, placebo controlled galacto-oligosaccharides (GOS) prebiotic supplement intervention and obtained stool samples at baseline and follow-up for gut microbiota sequencing and analyses. We report effects of the GOS intervention on self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may improve indices of pre-clinical anxiety. Gut microbiota research has captured the imagination of the scientific and lay community alike, yet we are now at a stage where this early enthusiasm will need to be met with rigorous research in humans. Our work makes an important contribution to this effort by combining a psychobiotic intervention in a human sample with comprehensive behavioural and gut microbiota measures.

Emerging evidence suggests interventions can improve childhood self-regulation. One intervention approach that has shown promise is Taekwondo martial arts instruction though little is known about its acceptability among stakeholders or its mechanisms of effect. We extend evidence on Taekwondo interventions in three ways: (1) testing the efficacy of a standard introductory course of Taekwondo; (2) assessing the acceptability of Taekwondo instruction among school children; and (3) investigating two self-regulatory mechanisms by which Taekwondo may operate (executive functions and motivation). This paper reports findings from a randomized control trial implementing a standard 11-week beginners’ course of Taekwondo. Participants were from a mixed-sex, non-selective UK primary school (N = 240, age range 7 to 11 years). Measures of self-regulation included teacher-rated effortful control, impulsivity, prosocial behavior and conduct problems; computer-based assessments of executive functions; and child self-reported expectancies and values to use self-regulation. Post-intervention, children in the Taekwondo condition were rated by teachers as having fewer symptoms of conduct problems and better effortful control (specifically attentional control), they also had better executive attention assessed by a Flanker Task. Effects were not found for teacher-rated inhibitory control, activation control, impulsivity and prosocial behavior, or for assessments of response inhibition, verbal working memory, and switching. Taekwondo was rated very positively by children. Finally, there was evidence that children who completed Taekwondo classes reported higher expectancies and values to use self-regulation and that expectancies and values mediated intervention effects on self-regulation. We conclude that short standard Taekwondo courses are well-received by pupils, improve attentional self-regulation and reduce symptoms of conduct-problems.

This systematic review brings together human psychobiotic interventions in children and adolescents (aged 6–25 years) to evaluate the efficacy of pre- and probiotic supplements on stress, anxiety, and cognitive outcomes. Psychobiotic interventions in animal studies highlighted sensitivity to effects during development and maturation in multiple domains from emotion to cognitive processing. Several translational psychobiotic interventions in humans have been carried out to assess effects on emotion and cognition during childhood and into adulthood. The findings illustrate that there are limited consistent psychobiotic effects in developing human populations, and this is proposed to be due to heterogeneity in the trials conducted. Consequentially, it is recommended that three specific factors are considered in future psychobiotic trials: (1) Specificity of population studied (e.g., patients, developmental age), (2) specificity of intervention, and (3) homogeneity in outcome measures.

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.

AbstractThe human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10–24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I2 was 12% and the pooled SMD was −0.03 (95% CI: −0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of −0.16 (95% CI: −0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths.