Parkinson’s disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson’s disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson’s disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson’s disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson’s disease. IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson’s disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson’s disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson’s disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.

Valentina Oppo and Giulia Serra equally contributed to this article. Francesca Morgante and Giovanni Cossu share senior authorship. Relevant disclosures and conflicts of interest are listed at the end of this article.

Among non-motor manifestations of Parkinson's Disease (PD), peripheral, sensory symptoms are particularly relevant. Smell dysfunction starts very early and frequently precedes the PD motor symptoms by years (being often a cue to the diagnosis). Moreover, olfactory system could be, together with gut, one of those peripheral sites where PD pathology first develops. Unlike smell loss, the relationship between PD and taste impairment is far less established. It can start early in the course of the disease but more frequently appears in advanced stages, in parallel with the advent of MCI, likely reflecting cortical involvement. Among PD patients has been demonstrated an increase in the frequency of the non-tasters for PROP (prototypical gustatory stimulus, 6-n-propylthiouracil), a genetically determined bitter taste which is mediated by TAS2RS38 receptor, and a significant increase of the recessive non-testing variant of this receptor. TAS2R38 receptors are expressed also in other tissues, such as in the epithelia of the gut and nasal cavities, where they can influence epithelial immunity ad its interaction with microbiota. Those pieces of evidence suggest that not only systematic assessment of taste and smell can be of a remarkable help for clinicians in the early diagnosis, but also that understanding the mechanisms of sensory involvement in PD could increase the knowledge of the pathophysiology of the disease.

Patients with a partial reduction of merosin due to mutations in the laminin-α2 chain gene usually present with a mild form of congenital muscular dystrophy or a limb-girdle-like muscular dystrophy. To our knowledge, cardiac impairment has never been reported in such patients. A longitudinal study of a patient with partial laminin-α2 deficiency secondary to mutations in the LAMA2 gene revealed dilated cardiomyopathy with ventricular arrhythmias. Is this a chance association or a novel phenotype?

Background: Recent data suggest that imbalances in the composition of the gut microbiome (GM) could exacerbate the progression of Parkinson's Disease (PD). The effect of Levodopa (LD) has been poorly assessed and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and, in particular, LCIG on GM and metabolome. Methods: Faecal DNA samples from 107 patients with clinical diagnosis of PD were analyzed by next-generation-sequencing of V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG-Group) (n= 38) and on LD (LD-Group) (n= 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve-Group). Faecal metabolic extracts were evaluated by Gas Chromatography Mass Spectrometry (GC-MS). Results: The multivariate analysis showed a significant higher abundance in the LCIG-Group of Enterobacteriaceae, Escherichia and Serratia compared to LD-Group. Compared to Naïve-Group, the univariate analysis showed a reduction of Blautia, Lachnospirae in LD-Group. Moreover, an Accepted Article This article is protected by copyright. All rights reserved increase of Proteobacteria, Enterobacteriaceae and a reduction of Firmicutes, Lachnospiraceae and Blautia was found in the LCIG-Group. No significant difference was found in the multivariate analysis of these comparisons. The LD-Group and LCIG-Group were associated to a metabolic profile linked to gut inflammation. Conclusion: Our results suggest that LD and mostly LCIG might significantly influence the microbiota composition and host/bacteria metabolism acting as stressors in precipitating a specific inflammatory intestinal microenviroment, potentially related to the PD state and progression.