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Background Autonomic nervous system ( ANS) regulation may be altered in functional diseases, including irritable bowel syndrome ( IBS), but published data are not clear to date. The aim of the study was to analyze ANS function in IBS subjects classified by Rome III criteria and healthy controls using standardized technique. Methods ANS activity was evaluated by autoregressive spectral analysis of RR interval and systolic arterial pressure variabilities, to obtain indices of sympatho-vagal modulation of the heart and of spontaneous cardiac baroreflex ( α index). A symptom list was used to score 18 somatic complaints (score 0-180) (4 SQ). Fatigue and stress were assessed through the use of a global scoring index (0-10). Key Results We enrolled 41 IBS subjects (29 F, age 40 ± 2 years) and 42 healthy matched controls. Heart rate was higher in IBS than control subjects (69 ± 2 vs 61 ± 1; p < 0.001). The total variance of RR interval variability, and α index, were significantly lower in IBS compared to controls (1983.12 ± 384.64 ms2 vs 4184.55 ± 649.59 ms2; 18.1 ± 2 ms/mmHg vs 29 ± 3 ms/mmHg; p < 0.01). The α index results showed an inverse correlation with stress scores and somatic symptoms. Conclusions & Inferences IBS subjects display a significant reduction in α index, an established marker of cardiac baroreflex. ANS dysfunction appears to be involved in the pathophysiology of IBS and its assessment may open new perspectives for clinical management of patients suffering from IBS. [ABSTRACT FROM AUTHOR]