Rodriguez-Sobstel, C. | bioRxiv Science

bioRxiv2026

Gut Microbiota Signatures of Brain and Peripheral gamma-amino butyric acid (GABA) in Healthy Adult Males

Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the mature human nervous system, plays a central role in neurodevelopment, emotion regulation, and sensory processing. Many psychiatric drugs act on the GABAergic system, highlighting its importance for healthy brain function. Individual differences in brain and circulating GABA levels have traditionally been attributed to genetic variation. However, several gut bacteria produce neuroactive compounds, including GABA, raising the possibility that microbial variation influences peripheral and central GABA levels and related measures in humans. This relationship remains largely unexplored. In a cross-sectional study of 251 healthy adults, we investigated associations between gut microbiota composition, central and peripheral GABA, and associated features. Brain GABA was quantified using magnetic resonance spectroscopy, blood GABA using enzyme-linked immunosorbent assays, and gut microbiota profiles using absolute and relative abundance measures derived from Flow Cytometry Fluorescent In Situ Hybridisation and 16S rRNA gene sequencing. Motor cortex GABA+ levels were positively associated with greater numbers of Bacteroides/Prevotella bacteria. A similar association was observed for blood GABA, which was additionally associated with greater numbers of lactic acid bacteria, Eubacterium rectale/Clostridium coccoides, and Clostridium histolyticum groups, and with predicted microbial gene pathways involved in GABA, propionate, and butyrate biosynthesis. No association was observed between brain and blood GABA concentrations. These findings provide new evidence for relationships between gut bacterial groups and central and peripheral GABA pools, supporting future longitudinal studies of causal links between gut microbiota and host GABA levels, as well as the potential for future intervention studies to influence GABAergic processing.

neuroscience↗

bioRxiv2024

The influence of trait intolerance of uncertainty on behavioural flexibility

Identifying and responding adaptively to a change in our environment is an essential skill. However, differences in our ability to detect and our disposition to react to these changes mean that some individuals are better equipped to deal with change than others. Here, we investigate whether intolerance of uncertainty, a transdiagnostic dimension of psychopathology, is associated with performance during a reversal learning task. We assessed task performance of 145 subjects using behavioural measures and computational modelling across two time points (approximately 12 days apart). Intolerance of uncertainty and its prospective and inhibitory subscales were associated with task performance, irrespective of self-reported levels of trait anxiety. Intolerance of uncertainty and its inhibitory subscale were positively associated with increased sensitivity to reinforcement from positive, but not negative, feedback. Furthermore, the inhibitory subscale was positively associated with better performance, both overall (as indexed by accuracy) and immediately following a change in reward contingencies (as indexed by perseveration). Lastly, the prospective subscale interacted with the extent to which choice was driven by expected value across time points. These findings provide novel evidence for how trait intolerance of uncertainty may modulate behavioural flexibility in changeable environments. The study points towards exciting avenues for further research into the development of IU-related behaviours across the lifespan and their implications for mental health.

animal behavior and cognition↗