Dysregulation of the Gut-Brain Axis, Dysbiosis and Influence of Numerous Factors on Gut Microbiota Associated Parkinson's Disease.

Parkinson's disease (PD) has been one of the substantial social, medical concerns and, burdens of the present time. PD is a gradually devastating neurodegenerative disorder of the neurological function marked with α-synucleinopathy affecting numerous regions of the brain-gut axis, as well as the central, enteric, and autonomic nervous system. Its etiology is a widely disputed topic. This review emphasizes to find out the correlation among the microbial composition and the observable disturbances in the metabolites of the microbial species and its impact on the immune response, which may have a concrete implication on the occurrence, persistence and, pathophysiology of PD via the gut-brain axis. An in-depth research and the database was developed from the available peer-reviewed articles to date (March 2020) utilizing numerous search engines like PubMed, MEDLINE and, other internet sources. Progressively increasing shreds of evidence have proved the fact that dysbiosis in the gut microbiome plays a central role in many neurological disorders, such as PD. Indeed, a disordered microbiome-gut-brain axis in PD could be focused on gastrointestinal afflictions that manifest primarily several years prior to the diagnosis, authenticating a concept wherein the pathological pathway progresses from the intestine reaching the brain. The microbiota greatly affects the bidirectional interaction between the brain and the gut via synchronized neurological, immunological, and neuroendocrine mechanisms. It can be concluded that a multitude of factors discussed in this review steadily induce the onset of dysbacteriosis that may exacerbate the etiologic mechanism of Parkinson's disease.

Kaur G ，Behl T ，Bungau S ，Kumar A ，Uddin MS ，Mehta V ，Zengin G ，Mathew B ，Shah MA ，Arora S ... -  《-》

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.

Caputi V ，Giron MC 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

The Gut-Brain Axis: Two Ways Signaling in Parkinson's Disease.

Parkinson's disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches.

Dogra N ，Mani RJ ，Katare DP 《-》

Brain-gut-microbiota axis in Parkinson's disease.

Mulak A ，Bonaz B 《-》

Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration.

Abnormal behavior of α-synuclein and prion proteins is the hallmark of Parkinson's disease (PD) and prion illnesses, respectively, being complex neurological disorders. A primary cause of protein aggregation, brain injury, and cognitive loss in prion illnesses is the misfolding of normal cellular prion proteins (PrPC) into an infectious form (PrPSc). Aggregation of α-synuclein causes disruptions in cellular processes in Parkinson's disease (PD), leading to loss of dopamine-producing neurons and motor symptoms. Alteration in the composition or activity of gut microbes may weaken the intestinal barrier and make it possible for prions to go from the gut to the brain. The gut-brain axis is linked to neuroinflammation; the metabolites produced by the gut microbiota affect the aggregation of α-synuclein, regulate inflammation and immunological responses, and may influence the course of the disease and neurotoxicity of proteins, even if their primary targets are distinct proteins. This thorough analysis explores the complex interactions that exist between the gut microbiota and neurodegenerative illnesses, particularly Parkinson's disease (PD) and prion disorders. The involvement of the gut microbiota, a complex collection of bacteria, archaea, fungi, viruses etc., in various neurological illnesses is becoming increasingly recognized. The gut microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, and intestinal barrier integrity through the gut-brain axis, which contributes to the development and progression of disease. The review delves into the molecular mechanisms that underlie these relationships, emphasizing the effects of microbial metabolites such as bacterial lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs) in regulating brain functioning. Additionally, it looks at how environmental influences and dietary decisions affect the gut microbiome and whether they could be risk factors for neurodegenerative illnesses. This study concludes by highlighting the critical role that the gut microbiota plays in the development of Parkinson's disease (PD) and prion disease. It also provides a promising direction for future research and possible treatment approaches. People afflicted by these difficult ailments may find hope in new preventive and therapeutic approaches if the role of the gut microbiota in these diseases is better understood.

Mahbub NU ，Islam MM ，Hong ST ，Chung HJ ... -  《Frontiers in Cellular and Infection Microbiology》