Integrated Macrogenomics and Metabolomics Explore Alterations and Correlation between Gut Microbiota and Serum Metabolites in Adult Epileptic Patients: A Pilot Study

Abstract

Epilepsy (EP) is a complex brain disorder showing a lot of unknows reasons. Recent studies showed that gut microbiota can influence epilepsy via the brain–gut axis. Nevertheless, the mechanism by which gut microbiota affects adult epilepsy still remains unclear. In this study, fecal and serum samples were obtained from patients with epilepsy and normal controls. Using an integrated analysis, sequencing was performed by macrogenomics and high-throughput targeted metabolomics with various bioinformatics approaches. The macrogenomic sequencing revealed significant changes in microbial structure in patients suffering from epilepsy. For example, at the phylum level, the relative abundance of Actinobacteria, Bacteroidetes and Proteobacteria showed an increase in the patients with epilepsy, whereas that of Firmicutes decreased. In addition, the patients with epilepsy had significantly differential metabolite profiles compared to normal controls, and five clusters with 21 metabolites, mainly containing the upregulation of some fatty acids and downregulation of some amino acids. Tryptophan (AUC = 91.81, p < 0.0001), kynurenine (AUC = 79.09, p < 0.01) and 7Z,10Z,13Z,16Z-Docosatetraenoic acid (AUC = 80.95, p < 0.01) may be used as potential diagnostic markers for epilepsy. Differential serum metabolites have effects on tryptophan metabolism, iron death and other pathways. Furthermore, a multiomic joint analysis observed a statistically significant correlation between the differential flora and the differential serum metabolites. In our findings, a macrogenomic analysis revealed the presence of dysregulated intestinal flora species and function in adult epileptic patients. Deeper metabolomic analyses revealed differences in serum metabolites between patients with epilepsy and healthy populations. Meanwhile, the multiomic combination showed connection between the gut microbes and circulating metabolites in the EP patients, which may be potential therapeutic targets.

Comparative analysis of the structural and compositional change of spotted sea bass (Lateolabrax maculatus) gut microflora following Aeromonas veronii infection and the effects of Lactobacillus plantarum on these changes

“…Additionally, Bacteroidetes was also a dominant phylum in the intestinal flora of healthy fish. Studies have shown that Bacteroides is related to the intestinal immune response, 63,64 and a higher abundance of Bacteroidetes helps to improve host immunity and contributes to the dynamic balance of gut microbiota. 65 In our study, compared with healthy fish, infected fish exhibited an increase in Proteobacteria abundance and a decrease in Bacteroidetes abundance over time.…”

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility

“…Promoting kynurenic acid production has been suggested as a strategy to mitigate spasms in animal models of infantile spasms (Mu et al, 2022a ). In a pilot study of patients with epilepsy, tryptophan and kynurenine were shown to have the potential as diagnostic markers for epilepsy (Zhou et al, 2023a ).…”

Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study

“…Recent studies increasingly unveil metabolic or lipid profiles distinguishing responders from nonresponders to anti-seizure medications (ASMs), yet their intricate role in epilepsy remains largely obscure due to complexity (8)(9)(10). Lipidomics is an emerging discipline dedicated to the systematic examination of lipids in biological systems, encompassing various fatty acids (FAs) and lipid subclasses.…”