To the Gut Microbiome and Beyond: The Brain-First or Body-First Hypothesis in Parkinson’s Disease

Nuzum, Nathan D.; Loughman, Amy; Szymlek‐Gay, Ewa A.; Teo, Wei‐Peng; Hendy, Ashlee M.; Macpherson, Helen

doi:10.3389/fmicb.2022.791213

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…nervous system and spreads to the CNS via the vagal nerve, which aligns with Braak's proposed staging [10]. These patients display more autonomic symptoms and a longer prodromal phase, with the development of non-motor symptoms such as gastrointestinal dysfunction, RBD, and hyposmia [9].…”

Section: Introduction Parkinson's Diseasesupporting

confidence: 71%

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The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson’s Disease

2023

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Parkinson’s Disease (PD), the second most common neurodegenerative disorder, is characterised by the severe loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and by the presence of Lewy bodies. PD is diagnosed upon the onset of motor symptoms, such as bradykinesia, resting tremor, rigidity, and postural instability. It is currently accepted that motor symptoms are preceded by non-motor features, such as gastrointestinal dysfunction. In fact, it has been proposed that PD might start in the gut and spread to the central nervous system. Growing evidence reports that the gut microbiota, which has been found to be altered in PD patients, influences the function of the central and enteric nervous systems. Altered expression of microRNAs (miRNAs) in PD patients has also been reported, many of which regulate key pathological mechanisms involved in PD pathogenesis, such as mitochondrial dysfunction and immunity. It remains unknown how gut microbiota regulates brain function; however, miRNAs have been highlighted as important players. Remarkably, numerous studies have depicted the ability of miRNAs to modulate and be regulated by the host’s gut microbiota. In this review, we summarize the experimental and clinical studies implicating mitochondrial dysfunction and immunity in PD. Moreover, we gather recent data on miRNA involvement in these two processes. Ultimately, we discuss the reciprocal crosstalk between gut microbiota and miRNAs. Studying the bidirectional interaction of gut microbiome–miRNA might elucidate the aetiology and pathogenesis of gut-first PD, which could lead to the application of miRNAs as potential biomarkers or therapeutical targets for PD.

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Section: Introduction Parkinson's Diseasesupporting

confidence: 71%

“…These patients present with fewer autonomic symptoms and a shorter prodromal phase, with less frequent development of non-motor symptoms such as RBD or hyposmia [9]. Present evidence reveals that most PD cases follow the body-first subtype [10].…”

Section: Introduction Parkinson's Diseasementioning

confidence: 70%

The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson’s Disease

2023

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“…Specifically, low butyrate levels correlate with severity of instability and postural problems (Tan et al, 2021). Lower abundance of Butyricimonas synergistica , a butyrate‐producer, was associated with worse PD non‐motor symptoms (Nuzum et al, 2023). On the other hand, Gmitterova et al (2020) have investigated endocrine cell markers, such as chromogranin A (CgA), which gradually increases in serum concentration from PD to PDD and LBD.…”

Section: Resultsmentioning

confidence: 99%

Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review

Mateo,

Marquès,

Domingo

et al. 2023

American J of Med Genetics Pt B

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Dementia is one of today's greatest public health challenges. Its high socio‐economic impact and difficulties in diagnosis and treatment are of increasing concern to an aging world population. In recent years, the study of the relationship between gut microbiota and different neurocognitive disorders has gained a considerable interest. Several studies have reported associations between gut microbiota dysbiosis and some types of dementia. Probiotics have been suggested to restore dysbiosis and to improve neurocognitive symptomatology in these dementias. Based on these previous findings, the available scientific evidence on the gut microbiota in humans affected by the most prevalent dementias, as well as the probiotic trials conducted in these patients in recent years, have been here reviewed. Decreased concentrations of short‐chain fatty acids (SCFA) and other bacterial metabolites appear to play a major role in the onset of neurocognitive symptoms in Alzheimer disease (AD) and Parkinson disease dementia (PDD). Increased abundance of proinflammatory taxa could be closely related to the more severe clinical symptoms in both, as well as in Lewy Bodies dementia. Important lack of information was noted in Frontotemporal dementia behavioral variant. Moreover, geographical differences in the composition of the gut microbiota have been reported in AD. Some potential beneficial effects of probiotics in AD and PDD have been reported. However, due to the controversial results further investigations are clearly necessary.

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“…The composition and function of intestinal microbiota are closely related to clinical characteristics of PD, including clinical symptoms, disease progression, and severity ( 41 , 42 ). The high-throughput sequencing studies found that intestinal microbiome changes in PD patients persisted in follow-up sampling 2 years later ( 43 ), and the most significant changes were the decrease of the bacterial group producing SCFAs (with anti-inflammatory effects) and the increase of the bacterial group producing LPS (with pro-inflammatory properties) ( 44 ).…”

Section: Microbiota–gut–brain Axis and Intestinal Microbiome Dysregul...mentioning

confidence: 99%

The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson’s disease

Meng

Chen

et al. 2023

Front. Neurol.

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Parkinson’s disease (PD) is a complex progressive neurodegenerative disease associated with aging. Its main pathological feature is the degeneration and loss of dopaminergic neurons related to the misfolding and aggregation of α-synuclein. The pathogenesis of PD has not yet been fully elucidated, and its occurrence and development process are closely related to the microbiota-gut-brain axis. Dysregulation of intestinal microbiota may promote the damage of the intestinal epithelial barrier, intestinal inflammation, and the upward diffusion of phosphorylated α-synuclein from the enteric nervous system (ENS) to the brain in susceptible individuals and further lead to gastrointestinal dysfunction, neuroinflammation, and neurodegeneration of the central nervous system (CNS) through the disordered microbiota-gut-brain axis. The present review aimed to summarize recent advancements in studies focusing on the role of the microbiota-gut-brain axis in the pathogenesis of PD, especially the mechanism of intestinal microbiome dysregulation, intestinal inflammation, and gastrointestinal dysfunction in PD. Maintaining or restoring homeostasis in the gut microenvironment by targeting the gut microbiome may provide future direction for the development of new biomarkers for early diagnosis of PD and therapeutic strategies to slow disease progression.

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To the Gut Microbiome and Beyond: The Brain-First or Body-First Hypothesis in Parkinson’s Disease

Cited by 9 publications

References 54 publications

The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson’s Disease

The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson’s Disease

Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review

The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson’s disease

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