Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease

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 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 stool SCFAs, inflammation, and zonulin. 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 PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.

Butyrate and related epigenetic changes link Parkinson’s disease to inflammatory bowel disease and depressive symptoms

“…In line with these findings, we confirm a positive correlation of Romboutsia and Roseburia with butyrate levels in PD patients (Fig. S1c) [22]. In addition, no other symptoms including gastrointestinal (Rome-III questionnaire; Wexner score), motor symptoms (the Unified Parkinson's Disease Rating Scale, UPDRS), nor non-motor symptoms (Non-Motor Symptoms Questionnaire, NMSQ; Non-Motor Symptoms Scale, NMSS) were linked with butyrate in PD patients.…”

“…First, we re-analyzed previously published [21,22] raw data on SCFA levels and 16S rRNA gene amplicon counts from stool samples of PD patients and healthy controls. The metagenomeSeq was used for differential microbial analysis [25].…”

“…Blood samples, clinical data, microbiome count data, inflammatory and permeability markers, and stool SCFA levels used in this study are from the Helsinki Parkinson microbiome cohort, and methodology of sampling, sample processing, and analysis have been described previously [21,22]. The study was approved by the ethics committee of the Hospital District of Helsinki and Uusimaa.…”

“…4a). Levels of inflammatory stool cytokines were derived from a previously published study of the same samples [22]. We also analyzed the methylated cytosines that were correlated with blood inflammatory cytokine levels.…”

The gut vascular barrier: a new player in the gut–liver–brain axis

“…It mainly leads to the systemic dissemination of gut luminal contents, and thus affects tissue function either directly or indirectly. Increasing evidence supports an essential and causative role of gut barrier disruption not only in intestinal disorders such as celiac disease [3] and inflammatory bowel disease (IBD) [4] but also in the development of liver diseases including non-alcoholic steatohepatitis (NASH) and cirrhosis [5][6][7], in metabolic syndrome [8,9], and in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, and autism spectrum disorder (ASD) [10][11][12][13]. The anatomical proximity of the liver to the Alterations in gut microbiota barrier homeostasis can lead to the development of intestinal and extraintestinal disease induced by a leaky gut.…”