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Investigating the association between the gut microbiome and cytokine concentrations in Parkinson's disease, schizophrenia, and PTSD
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  • Carlien Rust,
  • Leigh van den Heuvel,
  • Laila Asmal,
  • Jonathan Carr,
  • Etheresia Pretorius,
  • Soraya Seedat,
  • Sian Hemmings
Carlien Rust
Stellenbosch University Faculty of Medicine and Health Sciences

Corresponding Author:17524296@sun.ac.za

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Leigh van den Heuvel
Stellenbosch University Faculty of Medicine and Health Sciences
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Laila Asmal
Stellenbosch University Faculty of Medicine and Health Sciences
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Jonathan Carr
Stellenbosch University Faculty of Medicine and Health Sciences
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Etheresia Pretorius
Stellenbosch University
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Soraya Seedat
Stellenbosch University Faculty of Medicine and Health Sciences
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Sian Hemmings
Stellenbosch University Faculty of Medicine and Health Sciences
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Abstract

Introduction Studies have reported differences in the gut microbiome of neuropsychiatric disorder cases associated with increased intestinal permeability and inflammatory conditions. In support of inflammatory conditions, differences in cytokine concentration between cases and controls have also been reported in Parkinson’s disease (PD), schizophrenia (SCZ), and posttraumatic stress disorder (PTSD). This study correlated the gut microbiome with the existing inflammatory cytokine concentration data within each cohort including PD, SCZ, and PTSD. Methods Utilising the 16S rRNA (V4) gut microbial data available for PD, SCZ, and PTSD, the associations between significantly different cytokine concentrations and the gut microbiome were assessed. Alpha-diversity was evaluated using Shannon and Simpson diversity measures, whereas beta-diversity was assessed with the permutational multivariate analysis variance (PERMANOVA) adonis test. The differential relative abundance of gut microbial taxa associated with altered cytokine concentrations was determined using the Multivariate Association with Linear Models 2 (MaAsLin2) test. The significance threshold was set at α = 0.05 for all tests (both p-value or q-value) and used the Benjamini-Hochberg method to correct for multiple testing. Results The differences in cytokine concentrations between cases and controls were found not to be associated with alpha- or beta-diversity. We observed an association between IL-6 and the enriched relative abundance of Lactobacillus (q = 0.023, PD) and RFN20 (q = 0.011, SCZ), and depleted relative abundance of Coprococcus (q = 0.023, PD). Conclusion Elevated levels of pro-inflammatory cytokines, particularly IL-6, are observed across neuropsychiatric disorders and may be associated with a decrease in SCFA-producing taxa such as Faecalibacterium. Further research is needed to understand how dysregulated cytokine concentrations contribute to neuropsychiatric disorders and to explore molecular pathways involving cytokines and disease-specific proteins such as alpha-synuclein for potential therapeutic strategies.
25 Oct 2024Submitted to Immunity, Inflammation and Disease
28 Oct 2024Submission Checks Completed
28 Oct 2024Assigned to Editor
01 Nov 2024Reviewer(s) Assigned
20 Dec 2024Review(s) Completed, Editorial Evaluation Pending