Investigating the association between the gut microbiome and cytokine
concentrations in Parkinson's disease, schizophrenia, and PTSD
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.