The Structure Of Gut Microbiota In Idiopathic Parkinson’s Disease With Mild Cognition Impairment

Background and Aim:Gut bacteria play an important role in the pathogenesis of Parkinson’s disease(PD).However,the alteration of fecal microbiota in PD with cognitive impairment remains’ unexplored spectically.This study aimed to explore whether the gut microbiota of Cantonese patients with PD having mild cognitive impairment(PD-MCI)were different from those with PD having normal cognition(PD-NC)and from healthy controls(HC).Also,the study probed the association between altered gut microbiota and cognitive ability as well as short chain fatty acids(SCFAs)and cognitive ability in Cantonese patients with PD.Methods:A Case-control study was adopted for this experiment.The patients with PD were recruited and assessed in the Department of Neurology at the Guangdong Provincial People’s Hospital,Guangdong Province,China(from June 2018 to January 2019).A survey of basic information including age,gender,education,current medication,the degree of constipation(Wexner scale),alcohol and coffeine taking were filled out.Disease assessment were conducted in the case groups,including MDS-Unified Parkinson’s Disease Rating Scale Ⅲ,Hoehn-Yahr stage,Activity of Daily Living Scale,the 39-item Parkinson’s Disease Questionnaire and the duration of PD.Cognition abilities were estimated using the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA),and the scores were obtained from two other neuropsychological tests in each of the five cognitive domains.The fecal bacteria composition and SCFAs of subjects were analyzed using 16S rRNA sequencing and gas chromatography-mass spectrometry.The 16S sequences were analyzed using a combination of Mothur,UPARSE,R and PICRUSt software.Results:The full dataset included bacteria from 108 genera,42 families,24 orders,19 classes,and 11 phyla.An obvious discrepancy of fecal microbiota was found among the PD-MCI,PD-NC,and HC groups.The structures of fecal microbiota were also found to be significantly different between PD-MCI and PD-NC groups.After adjusting the influence of age,sex,body mass index,education,and constipation using the statistical method,the relative abundances of genera Alistipes,Barnesiella,Butyricimonas and Odoribacter were found to be higher in the feces of the PD-MCI group compared with the other two groups.Moreover,the abundance of genus Blautia and Ruminococcus decreased obviously in the PD-MCI group compared with the PD-NC group.Further,the abundance of genera Butyricimonas,Barnesiella were negatively correlated with MMSE scores(r=-0.32,P=0.002;r=-0.47,P=0.044)as well as genera Butyricimonas,Odoribacter and Alistipes negatively correlated with MoCA scores(r=-0.37,P=0.014;r=-0.33,P=0.040;r=-0.39,P=0.019).The microbial gene functions related to membrane transport were higher in the fecal microbiome of the PD group.No significant difference in the SCFAs level was found among the three groups.However,the isovaleric and isobutyric levels negatively correlated with the MMSE scores(r=-0.37,P=0.02;r=-0.34,P=0.03).Conclusion:Compared with HC and patients with PD-NC,the gut microbiota of Cantonese patients with PD-MCI was significantly altered,particularly manifesting in enriched genera from Porphyromonadaceae family and decreased the abundance of genera Blautia and Ruminococcus.Further,the abundance of genera Butyricimonas wad negatively correlated with cognition ability.