AUTHOR=Shen Yingjie , Li Changyu , Zhang Xi , Wang Yaolou , Zhang Haopeng , Yu Zhao , Gui Binbin , Hu Renjie , Li Qi , Gao Aili , Liang Hongsheng 

TITLE=Gut microbiota linked to hydrocephalus through inflammatory factors: a Mendelian randomization study

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1372051

DOI=10.3389/fimmu.2024.1372051

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus.</p></sec><sec><title>Methods</title><p>After removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results.</p></sec><sec><title>Results</title><p>After correction for <italic>P</italic>-values, <italic>Firmicutes</italic> (<italic>phylum</italic>) (OR, 0.34; 95%CI, 0.17–0.69; <italic>P</italic> = 2.71E-03, <italic>P</italic><sub>FDR</sub> = 2.44E-02) significantly reduced the risk of obstructive hydrocephalus. The remaining 18 different taxa of GM had potential causal relationships for different types of hydrocephalus. In addition, <italic>Firmicutes</italic> (<italic>phylum</italic>) decreased the risk of obstructive hydrocephalus by increasing levels of IL-17A (mediating effect = 21.01%), while <italic>Eubacterium ruminantium group</italic> (<italic>genus</italic>) increased the risk of normal-pressure hydrocephalus by decreasing levels of IL-27 (mediating effect = 7.48%).</p></sec><sec><title>Conclusion</title><p>We reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus.</p></sec>