Bidirectional associations between functional gastrointestinal disorders and epilepsy and the mediating role of mental health: A population-based study

Mar 13, 2026Journal of affective disorders

Two-way links between digestive disorders and epilepsy, with mental health as a possible influencing factor

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Abstract

Over 250,000 participants from the UK Biobank revealed significant bidirectional clinical risks between functional gastrointestinal disorders (FGIDs) and epilepsy.

Participants with FGIDs had a higher risk of developing epilepsy, with a hazard ratio of 1.77.
Epilepsy was found to be associated with an increased risk of FGIDs, with a hazard ratio of 1.57.
Mental health was linked to 2-6% of the bidirectional associations between FGIDs and epilepsy.
Genetic analysis suggested a connection between certain functional intestinal disorders and focal epilepsy with hippocampal sclerosis, indicated by an odds ratio of 1.62.
No consistent evidence was found to support the idea of causality from epilepsy to FGIDs.

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BACKGROUND: This study aimed to investigate the epidemiological and causal associations between functional gastrointestinal disorders (FGIDs) and epilepsy, with a focus on the mediating role of mental health.

METHODS: Based on the UK Biobank, Cox proportional hazard models were used to estimate the risk of incident epilepsy among participants with FGIDs and the risk of FGIDs among those with epilepsy. Mediation analysis quantified the contribution of mental health to these associations. The bidirectional causal relationships between these disorders were evaluated through Mendelian randomization (MR) analysis.

RESULTS: We identified significant bidirectional clinical risks between FGIDs and epilepsy among over 250,000 participants from the UK Biobank. Participants with FGIDs had a higher risk of epilepsy (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.51-2.09). Conversely, epilepsy was associated with a higher risk of FGIDs (HR 1.57, 95% CI 1.35-1.81). Mediation analyses indicated that mental health was associated with 2-6% of these bidirectional associations. MR analyses suggested a genetic link between other functional intestinal disorders and focal epilepsy with hippocampal sclerosis (odds ratio [OR] 1.62, 95% CI 1.09-2.41), but no consistent evidence for epilepsy-to-FGIDs causality.

CONCLUSION: This large-scale bidirectional cohort study highlights robust bidirectional links between FGIDs and epilepsy, with mental health modestly associated with these links. Clinically, integrated strategies targeting the gut-brain axis may incorporate psychological well-being alongside other contributory factors to optimize prevention and management.

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Bidirectional associations between functional gastrointestinal disorders and epilepsy and the mediating role of mental health: A population-based study

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