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Cited by 145Gut microbiota and healthParkinson's Disease Mechanisms and TreatmentsNutritional Studies and Diet

The DOI matches its Crossref record; 328 of the 328 references it cites were found in a registry or an index.

Diet in Parkinson’s Disease: Critical Role for the Microbiome

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Jackson, Aeja, Forsyth, Christopher B., Shaikh, Maliha, Voigt, Robin M., Engen, Phillip A., Ramirez, Vivian, Keshavarzian, Ali·2019·Frontiers in Neurology
DOI 10.3389/fneur.2019.01245PMC PMC6915094
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Abstract

Background. Parkinson’s disease (PD) is the most common movement disorder affecting up to 1% of the population above the age of 60 and 4–5% of those above the age of 85. Little progress has been made on efforts to prevent disease development or halt disease progression. Diet has emerged as a potential factor that may prevent the development or slow the progression of PD. In this review, we discuss evidence for a role for the intestinal microbiome in PD and how diet-associated changes in the microbiome may be a viable approach to prevent or modify disease progression. Methods. We reviewed studies demonstrating that dietary components/foods were related to risk for PD. We reviewed evidence for the dysregulated intestinal microbiome in PD patients including abnormal shifts in the intestinal microbiota composition (i.e., dysbiosis) characterized by a loss of short chain fatty acid (SCFA) bacteria and increased lipopolysaccharide (LPS) bacteria. We also examined several candidate mechanisms by which the microbiota can influence PD including the NLRP3 inflammasome, insulin resistance, mitochondrial function, vagal nerve signaling. Results. The PD-associated microbiome is associated with decreased production of SCFA and increased LPS and it is believed that these changes may contribute to the development or exacerbation of PD. Diet robustly impacts the intestinal microbiome and the Western diet is associated with increased risk for PD whereas the Mediterranean diet (including high intake of dietary fiber) decreases PD risk. Mechanistically this may be the consequence of changes in the relative abundance of SCFA-producing or LPS-containing bacteria in the intestinal microbiome with effects on intestinal barrier function, endotoxemia (i.e., systemic LPS), NLRP3 inflammasome activation, insulin resistance, and mitochondrial dysfunction, and the production of factors such as glucagon like peptide 1 (GLP-1) and brain derived neurotrophic factor (BDNF) as well as intestinal gluconeogenesis. Conclusions. This review summarizes a model of microbiota-gut-brain-axis regulation of neuroinflammation in PD including several new mechanisms. We conclude with the need for clinical trials in PD patients to test this model for beneficial effects of Mediterranean based high fiber diets.

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Figure 1 Mechanisms of communication between the intestinal microbiota and the brain. Diet robustly impacts the intestinal microbiota. Consumption of a Western diet (or components of the Western diet) promotes the growth of LPS-containing bacteria and reduces the abundance of SCFA-producing bacteria whereas consumption of a Mediterranean diet (or components of the Mediterranean diet) promotes the growth of SCFA-producing bacteria and reduces LPS-containing bacteria. This shift is highly significant because LPS-containing bacteria are pro-inflammatory, they disrupt intestinal barrier integrity and LPS binding to TLR4 stimulates a cascade of events including NLRP3 inflammasome activation, mitochondrial dysfunction, and insulin resistance culminating in neuroinflammation and neurodegeneration. In contrast, increased production of SCFA due to consumption of the Mediterranean diet (or components of the Mediterranean diet) fortifies the intestinal barrier, stimulates the intestinal L-cell production of GLP-1 and GIP which inhibits NLRP3 inflammasome activation and normalizes insulin resistance. SCFA also stimulate intestinal epithelial cell IGN and together with GLP-1/GIP stimulate the vagus nerve and brain BDNF which has numerous beneficial effects on the brain and which improves neuron insulin resistance all of which function to promote neuronal health. Characteristic features of the PD microbiome are similar to those observed following consumption of the Western diet (low SCFA-producing bacteria, high LPS-containing bacteria); therefore, dietary interventions such as the Mediterranean diet (or components of the Mediterranean diet) may be a viable approach to blunt neuroinflammation and improve neuronal function in PD. BDNF, brain derived neurotrophic factor; GIP, gastrointestinal peptide; GLP-1, glucagon like peptide 1; IGN, intestinal gluconeogenesis; IL-1β, interleukin 1 beta; LPS, lipopolysaccharide; NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; ROS, reactive oxygen species; SCFA, short chain fatty acids; TLR4, toll-like receptor 4.
Figure 1 Mechanisms of communication between the intestinal microbiota and the brain. Diet robustly impacts the intestinal microbiota. Consumption of a Western diet (or components of the Western diet) promotes the growth of LPS-containing bacteria and reduces the abundance of SCFA-producing bacteria whereas consumption of a Mediterranean diet (or components of the Mediterranean diet) promotes the growth of SCFA-producing bacteria and reduces LPS-containing bacteria. This shift is highly significant because LPS-containing bacteria are pro-inflammatory, they disrupt intestinal barrier integrity and LPS binding to TLR4 stimulates a cascade of events including NLRP3 inflammasome activation, mitochondrial dysfunction, and insulin resistance culminating in neuroinflammation and neurodegeneration. In contrast, increased production of SCFA due to consumption of the Mediterranean diet (or components of the Mediterranean diet) fortifies the intestinal barrier, stimulates the intestinal L-cell production of GLP-1 and GIP which inhibits NLRP3 inflammasome activation and normalizes insulin resistance. SCFA also stimulate intestinal epithelial cell IGN and together with GLP-1/GIP stimulate the vagus nerve and brain BDNF which has numerous beneficial effects on the brain and which improves neuron insulin resistance all of which function to promote neuronal health. Characteristic features of the PD microbiome are similar to those observed following consumption of the Western diet (low SCFA-producing bacteria, high LPS-containing bacteria); therefore, dietary interventions such as the Mediterranean diet (or components of the Mediterranean diet) may be a viable approach to blunt neuroinflammation and improve neuronal function in PD. BDNF, brain derived neurotrophic factor; GIP, gastrointestinal peptide; GLP-1, glucagon like peptide 1; IGN, intestinal gluconeogenesis; IL-1β, interleukin 1 beta; LPS, lipopolysaccharide; NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; ROS, reactive oxygen species; SCFA, short chain fatty acids; TLR4, toll-like receptor 4.CC BY · PubMed Central

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Metadata

Authors
Jackson, A., Forsyth, C. B., Shaikh, M., Voigt, R. M., Engen, P. A., Ramirez, V., & Keshavarzian, A.
Affiliations
Rush University Medical Center (US)
Corresponding author
Keshavarzian, Ali
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2019-12-10
Volume
10
Pages
1245-1245
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2019.01245
PMC
PMC6915094
OpenAlex
W2995752611
Cited by
145
References
328
Citations by year
2026: 16 · 2025: 22 · 2024: 21 · 2023: 17 · 2022: 35 · 2021: 18 · 2020: 13 · 2019: 1
FWCI
1.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
U.S. Department of Defense
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
Parkinson's disease, diet, gut microbiota, dysbiosis, short-chain fatty acids, lipopolysaccharide, Western diet, Mediterranean diet, dietary fiber, NLRP3 inflammasome, insulin resistance, mitochondrial dysfunction, microbiota-gut-brain axis, neuroinflammation, endotoxemia, intestinal barrier function, glucagon-like peptide-1, brain-derived neurotrophic factor, intestinal gluconeogenesis

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