Fecal microbiome alterations in treatment-naive de novo Parkinson's disease.

Gut microbiota alterations in Parkinson's disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.

Irritable Bowel Syndrome and Risk of Parkinson's Disease in Finland: A Nationwide Registry-Based Cohort Study.

BACKGROUND: The gastrointestinal tract is considered as a potential origin of Parkinson's disease (PD) pathology. Besides constipation, appendectomy and inflammatory bowel disease have also been associated with a higher PD-risk, but findings have been inconsistent. To date, there is only one previous study suggesting that irritable bowel syndrome (IBS) is associated with an increased risk of PD. OBJECTIVE: To evaluate whether IBS is associated with a higher risk of PD. METHODS: In this retrospective registry-based cohort study, we identified 28,150 patients that were diagnosed with IBS (IBS+) during the years 1998-2014, using data from the Finnish Care Register for Health Care. In addition, 98,789 IBS-free reference subjects (IBS-) of same age and gender and living in the same municipality were included. The study subjects were followed until the end of the year 2014 to analyze the incidence of PD. The association between IBS and PD was assessed by a Cox proportional hazards model. RESULTS: Diagnosis of IBS was associated with a higher hazard of PD with an adjusted hazard ratio (aHR) of 1.70 (95% CI 1.27-2.26). However, the ratio of hazard rates for PD between IBS+ and IBS- subjects was not constant over time. The Cox model with time-varying coefficient for IBS status showed that the hazard of PD was significantly higher in IBS patients only during the first two years of follow-up (aHR 2.96, 95% CI 1.78-4.92). CONCLUSION: Our findings indicate that the association between IBS and PD is likely explained by reverse causation and detection bias. It remains open whether IBS is an actual risk factor or a prodromal symptom of PD.

Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case-control study.

BACKGROUND: Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. OBJECTIVE: To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. METHODS: We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. RESULTS: The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. CONCLUSIONS: Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. © 2019 International Parkinson and Movement Disorder Society.

A former career as a male elite athlete--does it protect against type 2 diabetes in later life?

AIMS/HYPOTHESIS: The aim of this study was to determine the prevalence of impaired glucose regulation in male Finnish former elite athletes and age- and area-matched controls. We hypothesised that vigorous physical activity during young adulthood protects from disturbances in glucose regulation in later life. METHODS: In 2008, 392 former male elite athletes (mean age 72.7 ± 6.1 years) and 207 controls (mean age 71.6 ± 5.6 years) participated in a clinical study (participation rate: 50.6%). The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Participants without a history of diabetes (n = 537) underwent a 2 h 75 g OGTT. Current volume of leisure-time physical activity (LTPA) was determined by self-reported questionnaires and expressed in metabolic equivalent hours (MET-h). Data on reimbursable diabetes medication from participants and non-participants was obtained from the register of the Finnish Social Insurance Institution. RESULTS: Compared with the controls, the former elite athletes had a significantly lower risk of type 2 diabetes (OR 0.72, 95% CI 0.53, 0.98). The risk of type 2 diabetes decreased with increased LTPA volume (OR 0.98, 95% CI 0.97, 0.99 per 1 MET-h/week). The former elite athletes also had a significantly lower risk of impaired glucose tolerance (IGT) than the controls (OR 0.58, 95% CI 0.38, 0.87). CONCLUSIONS/INTERPRETATION: A former career as an elite athlete protected from both type 2 diabetes and IGT in later life. In addition, the volume of current LTPA was inversely associated with the prevalence of type 2 diabetes.