Abstract

Introduction: The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies. Conversely, evidence from clinical studies is still scarce. In recent years, the pivotal role of MGBA dysregulation in the pathophysiology of functional gastrointestinal disorders (FGID) has been recognized. With this background, we aimed to investigate the prevalence of FGID in patients with epilepsy (PWE) and the possible impact of bowel movement abnormalities on seizure recurrence.Methods: A total of 120 PWE and 113 age-, sex-, and BMI-matched healthy subjects (HS) were consecutively enrolled. A questionnaire to evaluate the presence of FGID (according to Rome III diagnostic criteria) was administrated to all participants. In a subgroup of drug-resistant patients, we administered an ad-hoc questionnaire combining Bristol stool charts and seizure diaries to evaluate seizure trends and bowel movement changes.Results: A higher prevalence of FGID in PWE (62.5%) than in HS (39.8%) was found (p < 0.001). The most frequently observed disorder was constipation, which was significantly higher in PWE than in HS (43.3 vs. 21.2%, p < 0.001), and was not associated with anti-seizure medication intake according to multivariable analysis. In drug-resistant patients, most seizures occurred during periods of altered bowel movements, especially constipation. A significant weak negative correlation between the number of days with seizures and the number of days with normal bowel movements was observed (p = 0.04). According to multivariable logistic regression analysis, FGID was significantly associated with temporal lobe epilepsy as compared with other lobar localization (p = 0.03).Conclusions: Our clinical findings shed new light on the complex relationship between epilepsy and the MGBA, suggesting a bidirectional link between bowel movement abnormalities and seizure occurrence. However, larger studies are required to better address this important topic.

Highlights

  • The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies

  • Their interaction relies on two main pathways, namely the autonomic nervous system and the hypothalamic-pituitary axis, which crosstalk in a bidirectional way at different levels, while other players, including the gut microbiota and its products, contribute to the functioning of the entire system [2]

  • Epileptic disorders can determine a multidimensional involvement of the gastrointestinal tract, including through ictal involvement of the brain structures subserving central control of autonomic functions, the possible interictal dysregulation of areas recurrently engaged by epileptic discharges, and the effects of anti-seizure medications (ASMs)

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Summary

Introduction

The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies. Epileptic disorders can determine a multidimensional involvement of the gastrointestinal tract, including through ictal involvement of the brain structures subserving central control of autonomic functions (as suggested by the wide range of visceral symptoms), the possible interictal dysregulation of areas recurrently engaged by epileptic discharges, and the effects of anti-seizure medications (ASMs) This matter is even more hazy when considering the possible role of gut-dependent neuroinflammation and dysbiosis in the genesis of seizures and epilepsy [15]. To shed light on such an intriguing issue, functional gastrointestinal disorders (FGID) could represent an ideal model by providing indirect information about gut-brain interactions according to the most recent pathophysiological conception [14] To investigate these interactions, we performed a clinical study exploring the prevalence and possible impact of FGID in a consecutive cohort of patients with epilepsy (PWE) as compared with healthy subjects (HS)

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