Alterations in the human gut microbiome in anti‐N‐methyl‐D‐aspartate receptor encephalitis

OBJECTIVE: To explore the diversity and composition of the fecal microbiota in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. METHODS: We enrolled 10 patients in the acute stage with naïve treatment, seven patients with relapse, 13 patients without relapse in the remission phase, and 12 paired healthy controls. The fecal microbiota in different groups was compared by 16S ribosomal DNA (rDNA) gene pyrosequencing. RESULTS: Prominent dysbiosis in the gut microbiome of patients with anti‐NMDAR encephalitis was found. Our primary findings showed that the overall species richness (alpha diversity indexes) of the microbiota was higher in patients than in controls (P < 0.05). Distance‐based community analysis revealed that the microbiota differed substantially within all subgroups of patients and controls (P < 0.05). The relative abundance of species heatmap showed a tendency toward depletion for some commensal genera, such as Prevotella_6, Bifidobacterium, Faecalibacterium, and other short‐chain fatty acid (SCFA)‐producing bacteria. Additionally, our results showed that all subgroups had a distinct bacterial species, with an increase in the genus Fusobacterium in the acute phase group and the genera Streptococcus and Parabacteroides in patients with relapse. However, the genus Bacteroides was very abundant in patients without relapse. Although the findings regarding the Firmicutes/Bacteroidetes (F/B) ratios across the four comparison groups were not statistically significant, the F/B ratio gradually increased in patients from the acute phase group (0.87), to the disease remission group with relapse (1.06), to the group without relapse (1.28), to the healthy group (1.63). INTERPRETATION: Patients with anti‐NMDAR encephalitis exhibit a substantial alteration in fecal microbiota composition.