Velma T E Aho1,2, Madelyn C Houser3,4, Pedro A B Pereira1,2, Jianjun Chang4, Knut Rudi5, Lars Paulin1, Vicki Hertzberg3, Petri Auvinen1, Malú G Tansey6,7, Filip Scheperjans8. 1. DNA Sequencing and Genomics Laboratory, Institute of Biotechnology, University of Helsinki, Viikinkaari 5D, 00790, Helsinki, Finland. 2. Department of Neurology, Helsinki University Hospital, and Department of Neurological Sciences (Neurology), University of Helsinki, ward K4A, Haartmaninkatu 4, FI-00290, Helsinki, Finland. 3. Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Rd, Atlanta, GA, 30322, USA. 4. Department of Physiology, Emory University School of Medicine, 615 Michael St, Atlanta, GA, 30322, USA. 5. Faculty of Chemistry, Biotechnology and Food Science (KBM), Norwegian University of Life Sciences, 1433, Oslo, Ås, Norway. 6. Department of Physiology, Emory University School of Medicine, 615 Michael St, Atlanta, GA, 30322, USA. mgtansey@UFL.edu. 7. Department of Neuroscience and Neurology, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, 1149 Newell Dr., Gainesville, FL, 32611, USA. mgtansey@UFL.edu. 8. Department of Neurology, Helsinki University Hospital, and Department of Neurological Sciences (Neurology), University of Helsinki, ward K4A, Haartmaninkatu 4, FI-00290, Helsinki, Finland. filip.scheperjans@hus.fi.
Abstract
BACKGROUND: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson's disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. METHODS: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. RESULTS: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. CONCLUSIONS: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
BACKGROUND: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson's disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PDpatients and controls to elucidate their interrelations and links to clinical manifestations of PD. METHODS: Stool and plasma samples and clinical data were collected from 55 PDpatients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. RESULTS: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. CONCLUSIONS: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
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