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The gut microbiota metabolite propionate ameliorates intestinal epithelial barrier dysfunction-mediated Parkinson’s disease via the AKT signaling pathway
Abstract
OBJECTIVE: Parkinson's disease is a common neurodegenerative disease. Here, we investigated the protective effect and potential mechanisms of propionate on the intestinal epithelial barrier in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease. METHODS: Gas chromatography was used to determine short-chain fatty acids (SCFA) concentrations in the fecal samples of Parkinson's disease patients and healthy controls. The stepping test was used to analyze forelimb akinesia, whisker test was used to analyze sensorimotor injury, cylinder test was used to analyze sensorimotor function, and Western blotting was used to analyze protein expression. RESULTS: The concentrations of SCFAs, including acetate, butyrate and propionate, were significantly downregulated in the fecal samples of Parkinson's disease patients, and among the SCFAs, propionate decreased the most. Propionate administration improved the stepping test score, whisker test score and cylinder test score of MPTP-induced Parkinson's disease mice. Additionally, propionate administration increased the protein expression of zonula occludens-1 and occludin. Moreover, the effects of propionate on motor behavior and the intestinal epithelial barrier were dependent on the proteirrserinc-threonine kinases (AKT) signaling pathway. More importantly, treatment with SC79, a specific AKT agonist, abolished the effects of propionate on the intestinal epithelial barrier and motor behavior. CONCLUSION: Our results demonstrated that propionate, which was decreased in the fecal samples of Parkinson's disease patients, exerted beneficial effects on intestinal epithelial barrier function and improved motor behavior in MPTP-induced Parkinson's disease mice through the AKT signaling pathway.
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“in vivo, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; a prodrug of the neurotoxin MPP+)-treated mice receiving propionate show a better performance in the stepping test, cylinder test and whisker test, in line with previous data [109,110]”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [109]
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“It has been found that propionate supplementation regulates zonula occludens-1 and occludin and has a positive effect on motor behavior and intestinal epithelial barrier through Akt signaling pathway [147].”
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BackgroundYazıcı, D., Öğülür, İ., Pat, Y., Babayev, H., Barletta, E., Ardıçlı, S., Imam, M. B., Huang, M., Koch, J., Li, M., et al. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101846 · Cited by 74
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“…propionic acids increase the expression levels of the tight junction proteins zonula occludens-1 and occludin on the epithelial barrier in patients with Parkinson’s disease (Huang et al., 2021), and valeric acid can reduce the incidence of necrotic enteritis in chickens (Onrust et al., 2018).”
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“Propionate administration improved motor behavior and the intestinal epithelial barrier by increasing the protein expression of zonula occludens-1 and occludin in MPTP-induced PD mice via the activation of the protein serine-threonine kinases (AKT) signaling pathway [227].”
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Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases
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“Reduced propionate levels in fecal samples might exert beneficial effects on intestinal epithelial barrier function and motor behavior via the AKT signaling pathway in a mouse model of MPTP-induced PD (Huang et al., 2021).”
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Metadata
- Authors
- Huang, T., Shi, H., Xu, Y., & Ji, L.
- Affiliations
- Jiangsu University (CN)
- Corresponding author
- Xu, Yuanfeng
- Ji, Lili
- Venue
- Neuroreport
- Published
- 2021-01-18
- Volume
- 32
- Issue
- 3
- Pages
- 244-251
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W3125042032
- Cited by
- 36
- References
- 25
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 2
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Parkinson's disease, propionate, short-chain fatty acids, gut microbiota, intestinal epithelial barrier, Akt signaling, MPTP-induced neurotoxicity, zonula occludens-1, occludin, motor behavior, SC79, fecal metabolites
- MeSH terms
- Gastrointestinal Microbiome, Acetates, Aged, Animals, Behavior, Animal, Benzopyrans, Butyrates, Disease Models, Animal, Fatty Acids, Volatile, Feces, Female, Humans, Intestinal Mucosa, Male, Middle Aged, Motor Activity, Parkinson Disease, Permeability, Propionates, Signal Transduction, Case-Control Studies, Parkinsonian Disorders, Proto-Oncogene Proteins c-akt, Mice, Occludin, Zonula Occludens-1 Protein
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