Parkinson's Disease Is Associated with Impaired Gut–Blood Barrier for Short‐Chain Fatty Acids
Abstract
Background: Short‐chain fatty acids (SCFAs) produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease (PD), which may stem from intestinal wall leakage. Gut function should be taken into consideration when conducting microbial‐metabolite research. Objective: The objective was to investigate synchronous changes of SCFAs in feces and plasma of patients with PD, taking constipation as a confounder to better disentangle the SCFA metabolism exclusively associated with PD. Methods: The concentrations of fecal and plasma SCFAs in 33 healthy control subjects and 95 patients with PD were measured using liquid and gas chromatography mass spectrometry, respectively. Patients with PD were divided into patients with PD without constipation (n = 35) and patients with PD with constipation (n = 60). Gut–blood barrier (GBB) permeability was assessed by plasma/fecal ratio of SCFA concentrations and fecal α1‐antitrypsin concentration. Results: Patients with PD displayed decreased concentrations of fecal acetic, propionic, and butyric acid and increased concentrations of plasma acetic and propionic acid. Fecal acetic, isobutyric, and isovaleric acid were lower and plasma acetic and propionic acid were higher in patients with PD with constipation than in patients with PD without constipation. Constipation aggravated GBB permeability in patients with PD. Combined fecal and plasma SCFAs could discriminate patients with PD from healthy control subjects. Fecal SCFAs, except propionic acid, were negatively correlated with disease severity, while plasma acetic, propionic, and valeric acid showed a positive correlation. Conclusions: Our study showed alterations of fecal and plasma SCFAs in patients with PD that were associated with an impaired GBB and might be aggravated by constipation. © 2022 International Parkinson and Movement Disorder Society.
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Diminished SCFA-producing species and SCFA levels are consistently reported in prodromal PD and PD patients compared with healthy controls, and may be correlated with clinical severity of PD.
“These findings are in concordance with a substantial body of literature that consistently reports diminished SCFAs-producing species and SCFA levels in prodromal stage of PD and PD patients compared to healthy controls, which may be correlated with the clinical severity of PD.52,322–331”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [330]
Cites
den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D.-J., & Bakker, B. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r036012 · Cited by 5,048 · see citing works
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838 · see citing works
Systematic review of levodopa dose equivalency reporting in Parkinson's disease
Tomlinson, C. L., Stowe, R. L., Patel, S., Rick, C., Gray, R. G., & Clarke, C. E. (2010) · Movement Disorders · doi:10.1002/mds.23429 · Cited by 4,232 · see citing works
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Morrison, D. J., & Preston, T. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1134082 · Cited by 3,781 · see citing works
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · see citing works
Braak, H., de Vos, R. A. I., Bohl, J., & Del Tredici, K. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.11.012 · Cited by 1,354 · see citing works
Colonic bacterial composition in Parkinson's disease
Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015) · Movement Disorders · doi:10.1002/mds.26307 · Cited by 1,281 · see citing works
A constipation scoring system to simplify evaluation and management of constipated patients
Agachan, F., Chen, T., Pfeifer, J., Reissman, P., & Wexner, S. D. (1996) · Diseases of the Colon & Rectum · doi:10.1007/bf02056950 · Cited by 1,258 · see citing works
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228 · see citing works
Unger, M. M., Spiegel, J., Dillmann, K.-U., Grundmann, D., Philippeit, H., Bürmann, J., Faßbender, K., Schwiertz, A., & Schäfer, K.-H. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.08.019 · Cited by 1,159 · see citing works
Parkinson's disease: a dual‐hit hypothesis
Hawkes, C. H., Del Tredici, K., & Braak, H. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00874.x · Cited by 1,021 · see citing works
Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study
Horsager, J., Andersen, K. B., Knudsen, K., Skjærbæk, C., Fedorova, T. D., Okkels, N., Schaeffer, E., Bonkat, S. K., Geday, J., Otto, M., et al. (2020) · Brain · doi:10.1093/brain/awaa238 · Cited by 782 · see citing works
Multiple roles of HDAC inhibition in neurodegenerative conditions
Chuang, D.-M., Leng, Y., Marinova, Z., Kim, H.-J., & Chiu, C.-T. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.06.002 · Cited by 676 · see citing works
Parkinson's Disease Society Brain Bank, London: overview and research.
Daniel, S. E., & Lees, A. J. (1993) · PubMed · Cited by 598 · see citing works
Microbiome–host systems interactions: protective effects of propionate upon the blood–brain barrier
Hoyles, L., Snelling, T., Umlai, U.-K., Nicholson, J. K., Carding, S. R., Glen, R. C., & McArthur, S. (2018) · Microbiome · doi:10.1186/s40168-018-0439-y · Cited by 591 · see citing works
Rome III: New standard for functional gastrointestinal disorders.
Drossman, D. A., & Dumitrascu, D. L. (2006) · PubMed · Cited by 584 · see citing works
α-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity
Kontopoulos, E., Parvin, J. D., & Feany, M. Β. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl243 · Cited by 539 · see citing works
Short-Chain Fatty Acids Regulate the Enteric Neurons and Control Gastrointestinal Motility in Rats
Soret, R., Chevalier, J., De Coppet, P., Poupeau, G., Derkinderen, P., Segain, J. P., & Neunlist, M. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.053 · Cited by 530 · see citing works
Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut
Roager, H. M., Hansen, L. B. S., Bahl, M. I., Frandsen, H. L., Carvalho, V., Gøbel, R. J., Dalgaard, M. D., Plichta, D. R., Sparholt, M. H., Vestergaard, H., et al. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.93 · Cited by 449 · see citing works
Aho, V. T. E., Houser, M. C., Pereira, P. A. B., Chang, J., Rudi, K., Paulin, L., Hertzberg, V., Auvinen, P., Tansey, M. G., & Scheperjans, F. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00427-6 · Cited by 435 · see citing works
Brain-First versus Gut-First Parkinson’s Disease: A Hypothesis
Borghammer, P., & Van Den Berge, N. (2019) · Journal of Parkinson’s Disease · doi:10.3233/jpd-191721 · Cited by 419 · see citing works
Stokholm, M. G., Danielsen, E. H., Hamilton‐Dutoit, S. J., & Borghammer, P. (2016) · Annals of Neurology · doi:10.1002/ana.24648 · Cited by 415 · see citing works
Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease
Qian, Y., Yang, X., Xu, S., Wu, C., Song, Y., Qin, N., Chen, S.-D., & Xiao, Q. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.016 · Cited by 409 · see citing works
Self-citationMicrobiota composition and metabolism are associated with gut function in Parkinson's disease
Cirstea, M. S., Yu, A. C., Golz, E., Sundvick, K., Kliger, D., Radisavljevic, N., Foulger, L. H., Mackenzie, M., Huan, T., Finlay, B. B., et al. (2020) · Movement Disorders · doi:10.1002/mds.28052 · Cited by 326 · see citing works
Schwiertz, A., Spiegel, J., Dillmann, U., Grundmann, D., Bürmann, J., Faßbender, K., Schäfer, K.-H., & Unger, M. M. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2018.02.022 · Cited by 318 · see citing works
Cersosimo, M. G., Raina, G. B., Pecci, C., Pellene, A., Calandra, C. R., Gutiérrez, C., Micheli, F. E., & Benarroch, E. E. (2013) · Journal of Neurology · doi:10.1007/s00415-012-6801-2 · Cited by 314 · see citing works
Kelly, L. P., Carvey, P. M., Keshavarzian, A., Shannon, K. M., Shaikh, M., Bakay, R. A. E., & Kordower, J. H. (2014) · Movement Disorders · doi:10.1002/mds.25736 · Cited by 308 · see citing works
Dodiya, H. B., Forsyth, C. B., Voigt, R. M., Engen, P. A., Patel, J., Shaikh, M., Green, S. J., Naqib, A., Roy, A., Kordower, J. H., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.12.012 · Cited by 305 · see citing works
Hou, Y.-F., Shan, C., Zhuang, S.-Y., Zhuang, Q.-Q., Ghosh, A., Zhu, K.-C., Kong, X.-K., Wang, S.-M., Gong, Y.-L., Yang, Y.-Y., et al. (2021) · Microbiome · doi:10.1186/s40168-020-00988-6 · Cited by 231 · see citing works
St. Laurent, R., O’Brien, L. M., & Ahmad, S. T. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.037 · Cited by 199 · see citing works
Paiva, I., Pinho, R., Pavlou, M. A., Hennion, M., Wales, P., Schütz, A.-L., Rajput, A., Szegő, É. M., Kerimoglu, C., Gerhardt, E., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx114 · Cited by 185 · see citing works
Zhuang, M., Shang, W., Ma, Q., Strappe, P., & Zhou, Z. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201801187 · Cited by 175 · see citing works
Constipation in parkinson's disease: Subjective symptoms, objective markers, and new perspectives
Knudsen, K., Krogh, K., Østergaard, K., & Borghammer, P. (2017) · Movement Disorders · doi:10.1002/mds.26866 · Cited by 169 · see citing works
Gut Metagenomics-Derived Genes as Potential Biomarkers of Parkinson’s Disease
Qian, Y., Yang, X., Xu, S., Huang, P., Li, B., Du, J., He, Y., Su, B., Xu, L.-M., Wang, L., et al. (2020) · Brain · doi:10.1093/brain/awaa201 · Cited by 139 · see citing works
Self-citationParkinson disease with constipation: clinical features and relevant factors
Yu, Q.-J., Yu, S., Zuo, L.-J., Lian, T., Hu, Y., Wang, R., Piao, Y., Guo, P. F., Liu, L., Jin, Z. Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-16790-8 · Cited by 136 · see citing works
Plasma Short‐Chain Fatty Acids in Patients With Parkinson's Disease
Shin, C., Lim, Y., Lim, H., & Ahn, T. (2020) · Movement Disorders · doi:10.1002/mds.28016 · Cited by 116 · see citing works
Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition
Kidd, S. K., & Schneider, J. S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.041 · Cited by 113 · see citing works
He, Q., Han, C., Huang, L., Yang, H., Hu, J., Chen, H., Dou, R., Ren, D., & Lin, H. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15586 · Cited by 96 · see citing works
Lin, X., Liu, Y., Ma, L., Ma, X., Shen, L., Ma, X., Chen, Z., Chen, H., Li, D., Su, Z., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02995-z · Cited by 83 · see citing works
Zhu, H. C., Zhao, J., Luo, C. Y., & Li, Q. Q. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9560-0 · Cited by 77 · see citing works
Analysis of gut microbiome and metabolite characteristics in patients with slow transit constipation
Tian, H., Chen, Q., Yang, B., Qin, H., & Li, N. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06500-2 · Cited by 68 · see citing works
Ostendorf, F., Metzdorf, J., Gold, R., Haghikia, A., & Tönges, L. (2020) · Molecules · doi:10.3390/molecules25112502 · Cited by 46 · see citing works
Jaworska, K., Konop, M., Maksymiuk, K. M., Hutsch, T., Dziekiewicz, M., Banaszkiewicz, A., & Ufnal, M. (2019) · Experimental Physiology · doi:10.1113/ep087773 · Cited by 36 · see citing works
Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrierPreprint
Hoyles, L., Snelling, T., Umlai, U. I., Nicholson, J. K., Carding, S. R., Glen, R. C., & McArthur, S. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/170548 · Cited by 31 · see citing works
Aho, V. T. E., Houser, M. C., Pereira, P. A. B., et al. (2020) · medRxiv · doi:10.1101/2020.06.15.20131011 · Cited by 28 · see citing works
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Varesi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012289 · Cited by 88 · see citing works
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- Authors
- Yang, X., Ai, P., He, X., Mo, C., Zhang, Y., Xu, S., Lai, Y., Qian, Y., & Xiao, Q.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Qian, Yiwei
- Xiao, Qin
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2022-05-24
- Volume
- 37
- Issue
- 8
- Pages
- 1634-1643
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W4282915163
- Cited by
- 82
- References
- 45
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 23 · 2023: 21 · 2022: 3
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81801254, 81870998, 81901283, 82171246)
- 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
- Parkinson's disease, short-chain fatty acids, intestinal permeability, gut microbiota, constipation, fecal SCFA, acetic acid, propionic acid, butyrate, isobutyric acid, isovaleric acid, valeric acid, alpha-1-antitrypsin, disease severity, biomarkers
- MeSH terms
- Constipation, Fatty Acids, Volatile, Feces, Humans, Parkinson Disease, Propionates
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