OBJECTIVE: To better understand the variations in gut microbiota in children with different types of epilepsy. METHODS: Thirty-seven children with epilepsy were included in the case group, which was further divided into focal (group A, n = 28) and generalized epilepsy groups (group B, n = 9) based on the origin and extent of the seizures. The focal epilepsy group was subdivided into the benign childhood epilepsy with centrotemporal spikes (BECT) (group C, n = 9) and non-BECT groups (group D, n = 19) based on the appearance of typical centrotemporal spikes or spike-wave complexes on the electroencephalogram (EEG). Additionally, 14 healthy children were selected as the control group (group E, n = 14). RESULTS: Significant differences were observed in the diversity and composition of gut microbiota between the case and control groups. At the genus level, the abundance of Megamonas (P = 0.001), Streptococcus (P<
0.001), Romboutsia (P = 0.001), Bacteroides (P<
0.05), and Escherichia/Shigella (P<
0.05) was significantly higher in the focal epilepsy group than in the control group (0.027 vs. 0.00009, P = 0.001
0.016 vs. 0.002, P<
0.001
0.013 vs. 0.002, P = 0.001
0.030 vs. 0.002, P<
0.05, respectively). Additionally, Escherichia/Shigella (P<
0.05) was more abundant in the case group compared to the control group (0.033 vs. 0.002, P<
0.05). Bacteroides (P<
0.05) was more abundant in the control group than in the case group. Megamonas (P<
0.001) and Collinsella (P<
0.05) were significantly more prevalent in the BECT group than in the control group (0.034 vs. 0.00009, P<
0.001
0.014 vs. 0.001, P<
0.05, respectively). In the non-BECT group, compared to the control group, Megamonas (P = 0.013), Streptococcus (P<
0.001), Romboutsia (P = 0.001), and Escherichia/Shigella (P<
0.05) were found in greater abundance (0.023 vs. 0.00009, P = 0.013
0.018 vs. 0.002, P<
0.001
0.014 vs. 0.002, P = 0.001
0.037 vs. 0.002, P<
0.05, respectively). CONCLUSIONS: Though, there were no statistically significant differences in gut microbiota between the different types of epilepsy, the gut microbiota of children with epilepsy significantly differed from that of healthy controls. The increased abundance of Escherichia/Shigella may lead to the worsening of clinical phenotypes and poor prognosis, and it could be a candidate biomarker to identify the focal epilepsy or even non-benign childhood epilepsy with centrotemporal spikes, potentially providing new therapeutic targets for the future.