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

Abstract

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.

Clinical Features and Gut Microbial Alterations in Anti-leucine-rich Glioma-Inactivated 1 Encephalitis—A Pilot Study

“…At the genus level, the patient group was characterized by a significantly increased Sphingomonas, Anaerofustis, Succinivibrio, Clostridium, and SMB53, while Faecalibacterium, Roseburia, Lachnospira, Ruminococcus, and Blautia were obviously decreased. In a previous report, feces from three subgroups of anti-NMDAR encephlitis patients showed enrichment of Bacteroides, Streptococcus and Parabacteroids, and Fusobacterium genera, respectively (12). The differences in specific microbial lanscapes between the two AEs indicate that the gut microbiota may be an effective marker for the differential diagnosis of anti-NMDAR encephalitis and anti-LGI1 encephalitis.…”

“…The correction of this index may be therapeutic methods or a good prognostic factor in anti-LGI1 encephalitis. However, the gut microbiota in anti-NMDAR encephalitis exhibited contrast results, characterized by higher or similar alpha diversity compared with HCs (12,15). Although both are AE subtypes, the triggers for anti-LGI1 encephalitis and anti-NMDAR encephalitis are likely to be distinct.…”

“…Recently, Gong et al observed an altered intestinal flora in 30 Chinese anti-NMDAR encephalitis patients compared with healthy controls. The study identified certain bacteria differentially distributed among patients in the acute phase, and those with or without relapse (12). Alterations in the composition of gut microbiota have also been reported in other autoimmune disorders such as multiple sclerosis (13) and neuromyelitis optica spectrum disorders (NMOSD) (14).…”

Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice

“…However, investigations of the MGB axis and autoimmunity for anti-NMDAR encephalitis are relatively rare. A recent clinical study demonstrated that anti-NMDAR encephalitis patients exhibit a substantial alteration in fecal microbiota composition relative to that of a small cohort of treatment-naïve patients 10 . Emerging animal studies have shown that mice devoid of gut microbiota from birth have reduced levels of NMDARs 11 , indicating possible connections between the gut microbiome and NMDARs.…”

Neuropsychiatric Ramifications of COVID-19: Short-Chain Fatty Acid Deficiency and Disturbance of Microbiota-Gut-Brain Axis Signaling

“…Several lines of evidence support this supposition. Changes in gut microbiome composition have been observed in several neuropsychiatric diseases [ 14 , 17 , 27 – 29 , 41 , 42 ]. Furthermore, SCFA-producing gut bacteria can modulate neuroinflammatory and neurodegenerative processes by producing specific metabolites, acetate, propionate, butyrate, and other less abundant SCFAs.…”