Intolerance of uncertainty as a core driver of anxiety and depression: The mediating role of the gut–brain axis

Intolerance of uncertainty (IU) is the tendency to react negatively to situations that are unclear, unpredictable, or lacking in information, and it is now regarded as a transdiagnostic risk factor for anxiety and depression. Research on the microbiota–gut–brain axis shows that the gut and brain communicate constantly and that disturbances in this communication accompany anxiety and depressive symptoms, yet the two literatures have developed largely apart. This study integrates them in a conceptual model in which IU (independent variable) influences anxiety and depression (dependent variables) partly through the gut–brain axis (mediator), via stress-system, immune–inflammatory, and behavioural pathways. Six hypotheses are derived and then illustrated in a simulation-based demonstration using a synthetic dataset (N = 400) analysed with parallel mediation, covarying age and gender, and 5,000 bootstrap resamples. In the simulated data, IU predicted gut–brain axis symptom burden (β = .42), which in turn predicted anxiety (β = .21) and depression (β = .31) over and above IU. A‍‍‍ significant part of an effect was mediated indirectly by anxiety (ab =.091, 95% CI [.047,.138]; 22% mediated) and depression (ab =.131, 95% CI [.081,.184]; 44% mediated), suggesting partial mediation. In terms of its implications, the paper also concludes by pointing out issues of assessment, psychological treatment, and integrated care while suggesting that the model should be tested in a real, longitudinal sample.