**7.4 Microbiota-gut-brain axis in Parkinson disease and its prodromes**

Currently it is well established that Parkinson's disease (PD) is not a pure movement disorder of the CNS but also a gastrointestinal disease [115–117], which affects the ENS [123–125]. The main premotor PD symptoms include rapid eye movement sleep behavior disorder, hyposmia, constipation and depression [126].

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia which results from the loss of physiological motor inhibition and is manifested with abnormal behavior during REM sleep. That disorder leads to varying degrees of complex motor activity which ranges from sleep talking to violent dream enacting behaviors potentially harmful for the subject or bed partner [127, 133].

In their study Heintz-Buschart et al. revealed differential abundances of gut microbial taxa (such as *Akkermansia*) in Parkinson disease (PD) and its prodromal state idiopathic REM sleep behavior disorder compared to healthy controls. The majority (about 80%) of the differential gut strains in patients with PD are very similar to those in subjects with idiopathic REM sleep behavior disorder. Most common are *Anaerotruncus* and *Bacteroides*, which correspond to non-motor symptoms of the disorders. Metagenomic sequencing of specific microbial samples allows the genomic reconstruction [23, 128]. Other studies registered reduction of microorganisms as *Faecalibacterium*, *Coprococcus*, *Blautia*, *Prevotella* and *Prevotellaceae* in gut of subjects, suffering from PD. These alterations are non-disease specific at a lower taxonomic level, for example at phylum stage, but at higher taxonomic level as genus or species, was registered some overlap between alpha synucleinopathies such as PD and multisystem atrophy (MSA) [3, 102].

It has been shown that PD patients with RBD exhibit much higher frequencies of phosphorylated asyn pathology in the colon and in the skin compared to PD patients without RBD [129]. Also, idiopathic RBD subjects exhibit marked pathology in the sympathetic and parasympathetic nervous system, but a relatively intact dopamine system [130].

For *Prevotella* such reduction has also been observed in RBD patients. Based on the attributed functional properties of these bacteria, such alterations could affect gut barrier integrity, short-chain fatty acid (SCFA) production, and inflammation. This would be in line with reports of a leaky gut and reduced levels of SCFAs and lipopolysaccharide binding protein in PD patients.

An interesting link between gut microbiota and asyn pathology could be cross-seeding of amyloid pathology induced by bacterial amyloid proteins such as curli.

So far, human microbiome studies in PD have been carried out exclusively in medicated patients, except for one study that included also idiopathic RBD patients *Influence of Gut Microbiota on Behavior and Its Disturbances DOI: http://dx.doi.org/10.5772/intechopen.85317*

[131]. While the PD associated microbiome alterations have been confirmed in drug adjusted analyses, confounding effects which could be result of COMT inhibitors intake cannot be excluded. Another potential confounder is colonic dysmotility, which may independently alter microbiota composition [132, 133].

Thus, observed brain and behavioral changes may be mediated by the absence of intestinal microbes directly or indirectly through one or more of the non-brainrelated alterations. The latest data show that the intrauterine environment is not sterile, and it can even be supposed that microbial metabolites of the intestine from the maternal microbes of the intestine may have an effect on the development of the fetal brain [75]. The altered signaling of the cecum to the brain secondary to the massive cecal dilation associated with this model may alter the development of the brain regions that process this input [88].
