Alteration of Gut Microbiota in Patients With Epilepsy and the Potential Index as a Biomarker

Abstract

Objective: To explore the structure and composition of the fecal microbiota of patients with epilepsy. Methods: Variations in the fecal microbiota between patients with epilepsy and healthy controls (HCs) from the same household were investigated and validated by utilizing 16S ribosomal RNA sequencing in two independent cohorts [exploration cohort (N = 55 patients and N = 46 HCs) and validation cohort (N = 13 patients and N = 10 HCs)]. Results: The alpha diversity indexes of the specimens from patients with epilepsy were much lower than those from the HCs (p < 0.05). The structure and composition of the fecal microbiota differed between patients with different clinical prognoses and between patients and HCs (Adonis: p < 0.05). Microbiome alterations in patients with epilepsy included increases in Actinobacteria and Verrucomicrobia and decreases in Proteobacteria at the phylum level and increases in Prevotella_9, Blautia, Bifidobacterium, and others at the genus level [linear discriminant analysis (LDA): 3.5] Patients with drug-resistant epilepsy showed enrichment of bacterial taxa in Actinobacteria, Verrucomicrobia, and Nitrospirae and the genera Blautia, Bifidobacterium, Subdoligranulum, Dialister, and Anaerostipes (Kruskal-Wallis test: p < 0.05). Analysis of gut microbiome indicated predictive ability for disease diagnosis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.97 (95% CI, 0.84-0.98). Applying the model to our validation cohort resulted in an AUC of 0.96 (95% CI, 0.75-0.97). Notably, the model could distinguish drug-resistant from drug-sensitive epilepsy (AUC = 0.85, 95% CI: 0.69-0.94). Conclusion: Patients with epilepsy exhibit substantial alterations of fecal microbiota composition, and specific gut commensal strains are altered depending on different clinical phenotypes and thus could serve as potential biomarkers for disease diagnosis.

Evidences for a Role of Gut Microbiota in Pathogenesis and Management of Epilepsy

“…In accordance with animal studies, a relationship between gut microbiota and epilepsy has been observed in humans. First, epileptic patients may present with altered microbiota [ 37 ]. Furthermore, it appears that patients with greater alterations of the microbiota composition are those with refractory epilepsy compared to those with drug-sensitive epilepsy and healthy controls [ 9 , 38 ].…”

The gut microbiome in drug‐resistant epilepsy

“…In the study by Peng et al, 42 the DSE group showed no statistically important differences compared to controls, while, in the study by Gong et al, it was reported that both DRE and DSE patients exhibited alterations in gut microbiota composition compared to controls. After further analysis, DRE patients’ intestines were found to be more dysbiotic, compared to DSE, with an increased abundance in rare flora 43 . It is possible that, once the alterations of fecal microbiota properties among different epileptic groups are adequately studied, gut profiling could serve as a potential biomarker for disease prognosis, in clinical practice.…”

“…Comparison of the structure and composition of the fecal microbiota among epileptic patients with different clinical phenotypes (DRE and DSE) has so far been conducted by two studies 42–43 . In the study by Peng et al, 42 the DSE group showed no statistically important differences compared to controls, while, in the study by Gong et al, it was reported that both DRE and DSE patients exhibited alterations in gut microbiota composition compared to controls.…”

“…Among patients with epilepsy, differences in the gut microbiota composition were reported depending on clinical phenotype (DRE or DSE), with DRE patients exhibiting enrichment of bacterial taxa in Actinobacteria, Verrucomicrobia, and Nitrospirae and the genera Blautia, Bifidobacterium, Subdoligranulum, Dialister, and Anaerostipes. 43 Another cohort of pediatric population included 14 infants with medically refractory epilepsy and 30 agematched healthy controls, whose microbiota profiling was done by 16S rDNA sequencing of stool samples. The calculation of α-diversity with the Shannon index for evenness revealed no statistically important difference between the two groups.…”

“…Of note, the results of subgroup analyses showed statistically important differences between the DRE, DSE, and control groups. Among patients with epilepsy, differences in the gut microbiota composition were reported depending on clinical phenotype (DRE or DSE), with DRE patients exhibiting enrichment of bacterial taxa in Actinobacteria, Verrucomicrobia, and Nitrospirae and the genera Blautia , Bifidobacterium , Subdoligranulum , Dialister , and Anaerostipes 43 …”