Impact of Gut Microbiota Dysbiosis in Treatment Outcomes of Guillain‐Barré Syndrome

BACKGROUND AND AIMS: The gut-microbiota plays a significant role in neuro-autoimmune diseases, like Guillain-Barré syndrome (GBS), a post-infectious disorder of the peripheral nervous system (PNS). By altering host immunity, gut dysbiosis may impact the standard therapeutic efficacy of intravenous immunoglobulin (IVIg) and plasma exchange (PE) and thereby, disease progression in GBS. In this study, we investigated the impact of gut-microbiota diversity on therapeutic outcomes of IVIg and PE in patients with GBS. METHODS: We enrolled 60 patients with GBS categorized into three treatment groups: IVIg-treated, PE, and supportive-care along with 60 age-sex-matched healthy controls from Bangladesh. Fecal microbial DNA was extracted at different timepoints and sequenced. Clinical and sequenced data were analyzed using the Qiime2-Dada2 pipeline. RESULTS: Gut-microbial diversity significantly differed in patients with GBS before and after treatment (Shannon: p = 0.037; Evenness: p = 0.012), particularly in IVIg-treated patients, showing significant changes after 6-month treatment (Shannon: p = 0.034; Evenness: p = 0.011). Beta diversity indicated microbiota restoration in IVIg-treated patients toward a healthy state after treatment (p ≤ 0.001). Phylum Actinobacteriota (p = 0.026), genera Bifidobacterium (p = 0.006), and Enterococcus (p ≤ 0.0001) were relatively abundant in severe patients. Mechanically ventilated patients showed significant gut-microbial diversity (Unweighted-UniFrac; p ≤ 0.001). Biomarker analysis identified a higher abundance of Eubacterium, Bacteroides, Escherichia-Shigella, and Actinomyces in GBS patients. INTERPRETATION: Our exploratory study indicates that gut microbiota dysbiosis is associated with GBS severity and IVIg-treatment outcomes. IVIg-treatment promoted partial restoration of microbial diversity, suggesting a potential immunomodulatory effect mediated through the microbiota. Further studies using meta-transcriptomics are warranted to define functional consequences of microbial shifts in treatment responses of GBS.