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000872759 1001_ $$0P:(DE-HGF)0$$aNerius, Michael$$b0
000872759 245__ $$aGI infections are associated with an increased risk of Parkinson’s disease
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000872759 520__ $$aWe have read with interest the recent publication of Perez-Pardo and colleagues1 reporting the role of the TLR4 in the gut–brain axis in Parkinson’s disease (PD). These findings prompted us to investigate the role of common GI infections (GIIs) in the pathogenesis of PD. In this prospective cohort study, we assessed the risk of PD in patients who previously suffered from GIIs compared with the control group not exposed to GIIs (table 1). At study entry (1 January 2005), the analysis sample from health claims data of the largest German health insurer consisted of2 28 485 individuals aged 50 years and older, which were followed for a mean time of 8.6 years (median=11.0 years; IQR=7.6 years). PD and GIIs were defined by ICD-10 codes as described in the supplementary material. Overall, 6195 individuals (2.7%) developed PD and 50 492 individuals (22.1%) were affected by any GII during the observation period between 2005 and 2015. The most frequent GIIs were those that caused infectious gastroenteritis and colitis of unspecified origin (IGCUs; 39 093 individuals, 17.1%), followed by viral intestinal infections (VIIs; 9328 individuals, 4.1%) and bacterial intestinal infections (BIIs; 9298 individuals, 4.1%). The cumulative incidence of PD was significantly higher among individuals with GIIs (p<0.001, online  supplementary figure S1). Multivariable analyses (table 2) using Cox regression to compute HRs revealed an increased risk of PD in patients with GIIs when compared with the control group (HR=1.42; 95% CI 1.33 to 1.52). Subgroup analyses (table 2) revealed positive associations of GIIs for men (HR=1.48; 95% CI 1.34 to 1.63), women (HR=1.38; 95% CI 1.27 to 1.50), individuals aged 70 years or older (HR=1.25; 95% CI 1.04 to 1.49) and individuals with (HR=1.40; 95% CI 1.23 to 1.59) or without chronic obstructive pulmonary disease (HR=1.43; 95% CI 1.33 to 1.54). To solidify our results, we performed sensitivity analyses and found no remarkable changes compared with our primary analysis (online supplementary table S1). In a secondary analysis, where we considered GIIs separately (online supplementary table S2), BIIs (HR=1.30; 95% CI 1.12 to 1.50), VIIs (HR=1.31; 95% CI 1.14 to 1.50) and IGCUs (HR=1.34; 95% CI 1.24 to 1.44) were each associated with an increased risk of PD.
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000872759 7001_ $$0P:(DE-HGF)0$$aDoblhammer, Gabriele$$b1
000872759 7001_ $$00000-0002-6933-5154$$aTamgüney, Gültekin$$b2$$eCorresponding author
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