Dysbiosis of gut microbiota in a selected population of Parkinson's patients

Pietrucci, Daniele; Cerroni, Rocco; Unida, Valeria; Farcomeni, Alessio; Pierantozzi, Mariangela; Mercuri, Nicola Biagio; Biocca, Silvia; Stefani, Alessandro; Desideri, Alessandro

doi:10.1016/j.parkreldis.2019.06.003

Cited by 171 publications

(169 citation statements)

References 31 publications

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“…Alignment with PD literature Reduced levels of SCFA producing bacteria 12,14,16,18,19,21,26,27 and elevated levels of probiotic bacteria in PD 14, 16,18,21,[25][26][27] have been reported before, and thus are confirmatory. Overabundance of opportunistic pathogens was a novel finding.…”

Section: Discussionsupporting

confidence: 78%

“…Several studies had found reduced levels of different SCFA producing bacteria in PD patients. 12,14,16,18,19,21,26,27 Our finding is therefore confirmatory, and expands on the list of PD-associated genera in these two taxonomic families. We and others noted that the decreasing levels of Lachnospiraceae correlate with increasing daily dose of levodopa, disease duration, 12 disease severity and motor impairment, 26 which suggest SCFA producing microorganisms diminish as a consequence of medication and/or advancing disease.…”

Section: Opportunistic Pathogenssupporting

confidence: 78%

“…12,14,16,18,19,21,26,27 Our finding is therefore confirmatory, and expands on the list of PD-associated genera in these two taxonomic families. We and others noted that the decreasing levels of Lachnospiraceae correlate with increasing daily dose of levodopa, disease duration, 12 disease severity and motor impairment, 26 which suggest SCFA producing microorganisms diminish as a consequence of medication and/or advancing disease. SCFA promote gastrointestinal motility, maintain integrity of the gut lining, and control inflammation in the gut and the brain, 47,48,[64][65][66] each of which are compromised in PD.…”

Section: Opportunistic Pathogenssupporting

confidence: 78%

“…animal models. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Every study that has compared the global composition of the gut microbiome in PD vs. controls found it to be significantly altered; in contrast, attempts to identify PD-associated microorganisms have produced inconsistent results. 31,32 Low reproducibility has been attributed to small sample sizes (missing true associations due to low power), relaxed statistical thresholds (inflating false positive results), and publishing without a replication dataset (required for genomic studies).…”

mentioning

confidence: 99%

“…Results were in agreement with population studies in detecting significant effects of sex, age, BMI, gastrointestinal issues and diet on the microbiome, 33,34 and with other PD studies in detecting evidence for dysbiosis in PD. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]…”

mentioning

confidence: 99%

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Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens

Wallen

Appah

Dean

et al. 2020

Preprint

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In Parkinson's disease (PD), gastrointestinal features are common and often precede the motor signs. Braak and colleagues proposed that PD may start in the gut, triggered by a pathogen, and spread to the brain. Numerous studies have examined the gut microbiome in PD, all found it to be altered, but found inconsistent results on associated microorganisms. Studies to date have been small (N=20 to 306) and are difficult to compare or combine due to varied methodology. We conducted a microbiome-wide association study (MWAS) with two large datasets for internal replication (N=333 and 507). We used uniform methodology when possible, interrogated confounders, and applied two statistical tests for concordance, followed by correlation network analysis to infer interactions. Fifteen genera were associated with PD at a microbiome-wide significance level, in both datasets, with both methods, with or without covariate adjustment. The associations were not independent, rather represented 3 clusters of co-occurring microorganisms. Cluster 1 was composed of opportunistic pathogens; all were elevated in PD. Cluster 2 were short-chain-fatty-acid producing bacteria; all were reduced in PD.Cluster 3 were carbohydrate-metabolizing probiotics; elevated in PD. Depletion of antiinflammatory short-chain-fatty-acid producing bacteria and elevated levels of probiotics are confirmatory. Overabundance of opportunistic pathogens is a novel finding and their identity provides a lead to experimentally test their role in PD. animal models. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Every study that has compared the global composition of the gut microbiome in PD vs. controls found it to be significantly altered; in contrast, attempts to identify PD-associated microorganisms have produced inconsistent results. 31,32 Low reproducibility has been attributed to small sample sizes (missing true associations due to low power), relaxed statistical thresholds (inflating false positive results), and publishing without a replication dataset (required for genomic studies). Differences in methods of DNA extraction, sequencing, bioinformatics and statistics can all contribute to inter-study variations. The choice of taxonomic resolution for analysis (PD has been tested at all levels from phylum to species) and the inconsistent taxonomic assignments and nomenclature used in various reference databases add to the confusion when comparing results. Last but not least, is confounding by heterogeneity in the populations that were studied: PD is heterogenous and so is the microbiome. PD subtypes cannot be readily identified thus patient populations are inevitably varied. A myriad of factors can affect the microbiome ranging from diet, health and medication to cultural habits, life-styles, race and geography. 33,34 Identifying microorganisms involved in the dysbiosis of the microbiome is essential for understanding their role in disease. We conducted a hypothesis-free microbiome-wide association study (MWAS) modeled after and usi...

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Section: Discussionsupporting

confidence: 78%

Section: Opportunistic Pathogenssupporting

confidence: 78%

Section: Opportunistic Pathogenssupporting

confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens

Wallen

Appah

Dean

et al. 2020

Preprint

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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 Human Microbiome—A Physiologic Perspective

Xiao,

Louwies,

Mars

et al. 2024

Comprehensive Physiology

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The human microbiome consists of the microorganisms associated with the body, such as bacteria, fungi, archaea, protozoa, and viruses, along with their gene content and products. These microbes are abundant in the digestive, respiratory, renal/urinary, and reproductive systems. While microbes found in other organs/tissues are often associated with diseases, some reports suggest their presence even in healthy individuals. Lack of microbial colonization does not indicate a lack of microbial influence, as their metabolites can affect distant locations through circulation. In a healthy state, these microbes maintain a mutualistic relationship and help shape the host's physiological functions. Unlike the host's genetic content, microbial gene content and expression are dynamic and influenced by factors such as ethnicity, genetic background, sex, age, lifestyle/diet, and psychological/physical conditions. Therefore, defining a healthy microbiome becomes challenging as it is context dependent and can vary over time for an individual. Although differences in microbial composition have been observed in various diseases, these changes may reflect host alterations rather than causing the disease itself. As the field is evolving, there is increased emphasis on understanding when changes in the microbiome are an important component of pathogenesis rather than the consequence of a disease state. This article focuses on the microbial component in the digestive and respiratory tracts—the primary sites colonized by microorganisms—and the physiological functions of microbial metabolites in these systems. It also discusses their physiological functions in the central nervous and cardiovascular systems, which have no microorganism colonization under healthy conditions based on human studies. © 2024 American Physiological Society. Compr Physiol 14:5491‐5519, 2024.

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Dysbiosis of gut microbiota in a selected population of Parkinson's patients

Cited by 171 publications

References 31 publications

Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens

Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens

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

The Human Microbiome—A Physiologic Perspective

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