Meta-analysis of the gut microbiome of Parkinson’s disease patients suggests alterations linked to intestinal inflammation

Abstract

The gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson's disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing 10 currently available 16S microbiome datasets to investigate whether underlying alterations in the gut microbiota of PD patients exist. We found consistent alterations in PD-associated microbiome, which are significant and robust to confounders across studies, although differences in microbiome structure between PD and controls are limited. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the families Lachnospiraceae and Ruminococcaceae, which are important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could explain the recurrent gastrointestinal symptoms affecting PD patients.

Parkinson' disease medication alters rat small intestinal motility and microbiota composition

“…were found to be the discriminating factor between all treated groups compared to the vehicle, in the ileum (Figure 4D). This is in agreement with the pooled data study of Romano et al 17 , where this genus was also the most strongly enriched in PD patients. Remarkably, a significant negative correlation was observed between species from the Lactobacillus genus and levodopa uptake (Supplementary Figure 2).…”

“…The often-reported increase in Lactobacillus, Bifidobacterium, Akkermansia, and the decrease in Lachnospiraceae and Prevotellaceae have been reported as a common finding among the several studies investigating the faecal gut microbiota composition between PD patients and HC subjects. 17 Remarkably, for most of these altered taxa (except Akkermansia), a similar alteration was observed in the small intestine of the healthy rat model employed in this study (i.e., not PD model). This infers that the observed changes in microbiota composition in PD patients is, at least partly, due to the PD medication and not the disease per se.…”

“…Recently, the sequencing data from most of these studies have been pooled and re-analysed in order to identify common alterations in the gut microbiota of PD patients. 17 Romano et al concluded that it was impossible to determine whether the changes in microbiota composition were causally linked to the disease per se in the pooled data analysis due to confounding factors such as PD medication, which was considerably variable among the studies included. 17 Indeed PD medication is a major differentiating factor between PD patients and HC subjects and only a few studies 1,6,9,12,14 investigated or reported the effect of medication on the microbiota profiles in PD patients.…”

“…17 Romano et al concluded that it was impossible to determine whether the changes in microbiota composition were causally linked to the disease per se in the pooled data analysis due to confounding factors such as PD medication, which was considerably variable among the studies included. 17 Indeed PD medication is a major differentiating factor between PD patients and HC subjects and only a few studies 1,6,9,12,14 investigated or reported the effect of medication on the microbiota profiles in PD patients. So far, no studies were performed in healthy subjects, which is required to determine whether the PD medication per se affects the microbiota composition.…”

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

“…Prevotella species associated with detrimental impacts on intestinal barrier integrity are enriched in IBS patients and in models of intestinal inflammation [ 52 , 113 ] and may promote inflammatory arthritis [ 3 , 104 , 126 ]. However, other reports identify beneficial impacts of Prevotella species on glucose metabolism [ 60 ], and there are conflicting associations with Parkinson’s disease progression [ 97 ].…”