*2.1. Parkinson's Disease and Alzheimer's Disease*

Two of the most prevalent neurodegenerative diseases are Parkinson's disease (PD) and Alzheimer's disease (AD), with the latter being more common. They are both progressive and associated with advanced age, but their exact causes are not fully understood, although it is believed that a combination of both genetic and environmental factors play a role in their development and progression. AD is mostly associated with memory loss, disorientation, and behavioral issues. In the brain, there is a progressive loss of neurons and the formation of amyloid plaques and neurofibrillary tangles originating from the amyloid-beta (Aβ) precursor protein (APP). PD is characterized by abnormal accumulation and aggregation of alpha-synuclein in the form of Lewy bodies and loss of dopaminergic neurons in the substantia nigra, which causes dopamine deficiency. The most common

motor symptoms are tremors, stiffness, bradykinesia, and loss of coordination, with accompanying cognitive disorders such as depression, anxiety, and apathy [39,40].

The composition of the intestinal microbiota is not only important for maintaining the proper health of the body but can also affect the physiological, behavioral, and cognitive functions of the brain. There is ample evidence for differences in the microbiome between healthy individuals and PD patients. Patients suffering from PD were characterized by a reduced presence of *Prevotellaceae* bacteria and an increased number of *Enterobacteriaceae* bacteria. Currently, it is difficult to clearly define the role of SCFAs in the pathogenesis of neurodegenerative diseases. However, the vast majority of publications indicate pathological SCFA activity in PD patients. Studies in mice overexpressing alpha-synuclein demonstrate the effect of a microbial-free environment on the elimination of the PD phenotype, and oral feeding of SCFAs to the same mice restores the neuropathology associated with PD. Counterintuitively, SCFA administration to patients increases motor dysfunction and inflammation [41–43]. According to a study published in 2019, bacteria from the *Prevotellaceae* family have been found to provide high levels of health-promoting neuroactive SCFAs, which in turn contribute to a healthy environment in the gut [44]. Decreased *Prevotella* abundance has also been linked to multiple sclerosis (MS), type 1 diabetes, and autism spectrum disorders. Furthermore, the presence of *Prevotella* is significantly influenced by a plant-based diet. Increased abundance of *Lactobacillus* has been associated with type 2 diabetes and constipation, suggesting that the prognostic value of *Lactobacillus* is not specific to PD. Multiple bacterial taxa have been reported to be altered in individuals with PD. Potential interactions between them indicate that the effects of altered gut microbiota in PD may be the result of many complex cascades of events within the entire gut microbiota as well as relationships with the host [45].

Recent results suggest a strong link between the pathogenesis of AD and intestinal microbiota dysfunctions. Studies conducted on the ADLPAPT mouse model of AD show that changes in the composition of the intestinal microflora led to a loss of intestinal epithelial integrity, which in turn caused systemic inflammation. Intestinal abnormalities coincided with Aβ deposition, Tau protein pathology, progressive gliosis, and cognitive impairment in the animals. It was also noted that the transplantation of microbiota from healthy animals into animals suffering from AD significantly attenuated the progression of AD pathogenesis [46]. A number of studies indicate significant changes in the composition of the gut microbiota during the course of AD. There was an increase in *Firmicutes/Bacteroidetes* and a decrease in *Actinobacteria* and SCFA-producing bacteria in AD mice [47,48]. A large body of research supports the idea that the gut microbiome in mouse models of AD is less diverse than in wild type (WT) mice [48–52]. Some association has also been noted between the presence of butyrate- and lactate-producing bacteria. Furthermore, a decrease in the number of butyrate-producing *Faecalibacterium* and an increase in the number of lactateproducing bacteria of the *Bifidobacterium* family were found using the sequencing of 16S rRNA from stool samples [50]. Metagenomic studies have proven the relationship between *Lachnospiraceae* and type 2 diabetes. The aforementioned family of bacteria contributes to the development of diabetes, which, along with insulin resistance, is one of the risk factors for AD [53–55]. Functional studies show that *Pseudomonas aeruginosa* infection can increase endothelial Tau phosphorylation and permeability, a common pathophysiological mechanism in the genesis of Alzheimer's disease [56,57]. To date, little has been established about the interactions between pathogenic and non-pathogenic *Pseudomonas* strains in the bodies of patients with AD. Future research should focus on further understanding the role of specific bacterial clusters in the gut microbiome in the pathogenesis of AD [58]. A study where the young WT mice received a gut microbiota transplant from old AD mice has shown that this intervention significantly impaired the recovery from a traumatic brain injury. The study has also shown increased activation of microglia and macrophages and reduced motor recovery. In addition, there was a higher relative count of *Muribaculum* bacteria and a decrease in *Lactobacillus johnsonii* in WT mice transplanted with a microbiome

derived from old AD mice. Another study confirms that the microflora derived from AD mice has a significant effect on the deterioration of the neurological response [59].

#### *2.2. Microbiome in Huntington's Disease*
