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Cited by 25Gut microbiota and healthParkinson's Disease Mechanisms and TreatmentsGastrointestinal motility and disorders

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

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Liu, Jiaji, Chen, Qi, Su, Ruijun·2024·Medicine
DOI 10.1097/md.0000000000037960PMC PMC11049718
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Abstract

Short-chain fatty acids (SCFAs) are, the metabolic byproducts of intestinal microbiota that, are generated through anaerobic fermentation of undigested dietary fibers. SCFAs play a pivotal role in numerous physiological functions within the human body, including maintaining intestinal mucosal health, modulating immune functions, and regulating energy metabolism. In recent years, extensive research evidence has indicated that SCFAs are significantly involved in the onset and progression of Parkinson disease (PD). However, the precise mechanisms remain elusive. This review comprehensively summarizes the progress in understanding how SCFAs impact PD pathogenesis and the underlying mechanisms. Primarily, we delve into the synthesis, metabolism, and signal transduction of SCFAs within the human body. Subsequently, an analysis of SCFA levels in patients with PD is presented. Furthermore, we expound upon the mechanisms through which SCFAs induce inflammatory responses, oxidative stress, abnormal aggregation of alpha-synuclein, and the intricacies of the gut-brain axis. Finally, we provide a critical analysis and explore the potential therapeutic role of SCFAs as promising targets for treating PD.

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  • In vitro data indicate that SCFAs might contribute to α-synuclein pathogenesis.

    “At the molecular level, in vitro data indicate that SCFAs might contribute to α-synuclein pathogenesis.”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [124]

    Section 4.3 reports that SCFAs downregulate α-synuclein aggregation and that sodium butyrate promotes its degradation in cell-based and rotenone-induced models. Those findings point away from the claimed contribution to α-synuclein pathogenesis, rather than supporting it. (LLM, conf=0.86)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • SCFAs are shown to modulate activation of the NLRP3 inflammasome via GPR43 activation and modulation of autophagy pathways via autophagy genes including Atg5 and the PI3K/Akt/mTOR pathway.

    “SCFAs are shown to modulate activation of the NLRP3 inflammasome via GPR43 activation and modulation of autophagy pathways via autophagy genes including Atg5 and the PI3K/Akt/mTOR pathway. [123, 124].”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [124]

    Section 4.3 (page unavailable) reports that sodium butyrate activates Atg5 expression and inhibits the PI3K/Akt/mTOR pathway to promote autophagic degradation of α-synuclein. Section 3.2 says SCFAs activate GPR43 to regulate inflammation through NF-κB, but it does not link GPR43 activation to NLRP3 inflammasome activation. That specific mechanism is not supported by our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Liu, J., Chen, Q., & Su, R.
Affiliations
  • Inner Mongolia Medical University (CN)
  • Ningxia Medical University (CN)
Corresponding author
Su, Ruijun
ORCID
Venue
Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2024-04-26
Volume
103
Issue
17
Pages
e37960
ISSN
  • 0025-7974 (ISSN-L)
  • 1536-5964
DOI
10.1097/md.0000000000037960
PMC
PMC11049718
OpenAlex
W4395677123
Cited by
25
References
14
Citations by year
2026: 8 · 2025: 14 · 2024: 3
FWCI
1.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Natural Science Foundation of Inner Mongolia
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
short-chain fatty acids, Parkinson's disease, gut microbiota metabolites, gut-brain axis, alpha-synuclein aggregation, neuroinflammation, oxidative stress, dietary fiber fermentation, Parkinson's disease treatment
MeSH terms
Gastrointestinal Microbiome, Brain-Gut Axis, Fatty Acids, Volatile, Humans, Parkinson Disease, Oxidative Stress

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