Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair, Arun T.; Ramachandran, Vadivelan; Joghee, Nanjan Moola; Antony, Shanish; Ramalingam, Gopalakrishnan

doi:10.5056/jnm17105

Cited by 118 publications

(97 citation statements)

References 145 publications

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“…In fact, α-synucleinopathy of the ENS has been suggested to be an early indicator of PD pathology. 21 The regular APP expression in the ENS supports the theory of the ENS involvement also in AD. The APP transgenic mice develop accumulation of Aβ in the enteric neurons leading to a decrease in enteric neuron abundance, dysmotility, and increased vulnerability to inflammation.…”

Section: Enteric Nervous Systemsupporting

confidence: 60%

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Kowalski

Mulak

2019

J Neurogastroenterol Motil

562

450

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Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer’s disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The Aβ seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.

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Section: Enteric Nervous Systemsupporting

confidence: 60%

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Kowalski

Mulak

2019

J Neurogastroenterol Motil

562

450

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“…The gut microbiome has been increasingly implicated in disrupting health and behavior [10][11][12][13][14]. Recent molecular studies discovered that the taxonomic composition of human intestines is host specific [15,16], relatively stable over a time [16,17], and linked to many human diseases [18][19][20][21][22]. Microbial communities in the gut produce extensive amounts of metabolic products, interact intimately with human cells, and play an important role in maintaining many physiological processes and functions [23,24].…”

Section: Introductionmentioning

confidence: 99%

The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

Surathu

Raplee

et al. 2020

BMC Genomics

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Background: Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. Methods: This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance. Results: There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group). Conclusions: Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.

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“…50 Several researchers hypothesize that gut inflammation and deposition of aberrant α-synuclein fibrils in the ENS initiate the process that leads to a retrograde spread via the vagal and the glossopharyngeal nerve trunks to the neuronal tissue in the CNS (Figure). 51,52 This is supported by the fact that α-synuclein deposits have been found early on, in the ENS of individuals with PD. 53 However, a recent study by Lee et al, 54 in patients with PD (n = 35) compared deposition of α-synuclein in intestinal mucosal ENS as compared to controls (n = 52) to assess GI dysfunction.…”

Section: Evidence For the Presence Of Inflammation In The Enteric Nermentioning

confidence: 87%

Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation

Dutta

Verma

Jain

et al. 2019

J Neurogastroenterol Motil

118

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The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson’s disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread “prion like” via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

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Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Cited by 118 publications

References 145 publications

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation

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