Integrative analysis of purine metabolites and gut microbiota in patients with neuromyelitis optica spectrum disorders after mycophenolate mofetil treatment

Abstract

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a recurring inflammatory demyelinating disease that is commonly observed in Asian countries like China. Prior investigations have shown that mycophenolate mofetil (MMF) with better biocompatibility compared to azathioprine (AZA), and can prevent relapses of NMOSD, but the efficacy was controversially reported in different NMOSD cases. We aimed to explore the factors that weaken efficacy of MMF in NMOSD. Methods A total of 34 NMOSD patients treated with MMF were prospectively enrolled and grouped according to the therapeutic efficacy as effective group (EG, n = 23) versus less-effective group (LEG, n = 11). The purine metabolites were profiled in serum samples and gut microbiota was analyzed using 16S rRNA sequencing with stool samples from the same patients. Results Purine salvage pathway (PSP) metabolites (inosine, hypoxanthine, xanthine, guanine and uric acid) in the serum of NMOSD patients were elevated in the LEG compared to EG (p < 0.05). Additionally, the richness and microbial diversity of gut microbiota was found to be similar between EG and LEG patients. However, LEG patients had increased presence of Clostridium and Synergistes but decreased abundance of the Coprococcus genus. Conclusions The PSP metabolites and composition of the gut microbiota were changed between patients with or without optimal clinical response after MMF treatment. This may help us to understand the pharmacodynamics of MMF in NMOSD.

Keywords

• Neuromyelitis Optica Spectrum Disorders
• Mycophenolate Mofetil
• Gut Microbiota
• Therapeutic Efficacy
• PSP Metabolites