Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease
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Abstract
Background: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
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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 [327]
A decrease in short-chain fatty acids (SCFAs) in feces has been implicated in the development of Parkinson's disease.
“a decrease in short-chain fatty acids (SCFAs) in feces has been implicated in the development of PD [66]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [66]
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- Authors
- 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.
- Affiliations
- University of Helsinki (FI)
- Emory University (US)
- Norwegian University of Life Sciences (NO)
- Corresponding author
- Tansey, Malú G.
- Scheperjans, Filip
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2021-02-08
- Volume
- 16
- Issue
- 1
- Pages
- 6-6
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC7869249
- OpenAlex
- W3127379712
- Cited by
- 435
- References
- 56
- Citations by year
- 2026: 58 · 2025: 96 · 2024: 93 · 2023: 86 · 2022: 81 · 2021: 20
- FWCI
- 21.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (1R01NS092122)
- Michael J. Fox Foundation for Parkinson's Research (LRRK2 in immunity)
- Academy of Finland (295724, 310835)
- Suomen Lääketieteen Säätiö
- Helsingin Yliopisto (UAK1014004, UAK1014005, TYH2018224)
- 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, gut microbiota, short-chain fatty acids, intestinal permeability, intestinal barrier, inflammation, calprotectin, zonulin, neutrophil gelatinase-associated lipocalin, interleukin-8, IL-1β, sex differences, age of onset, motor and non-motor symptoms, microbiota-host interactions
- MeSH terms
- Gastrointestinal Microbiome, Aged, Fatty Acids, Volatile, Female, Haptoglobins, Humans, Inflammation, Male, Middle Aged, Parkinson Disease, Protein Precursors, Biomarkers
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