Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients

Liu, Lanzhi; Luo, Zhaohui; Liu, Fan; Shang, Danqing; Qiu, Dongxu; Xiao, Jiangjian; Zhou, Xiaoliang; Chen, Si; Wu, Junfang; Li, Jing

doi:10.1016/j.msard.2021.102779

Cited by 1 publication

(1 citation statement)

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“…Clinical data that was collected included follow-up time, relapses and EDSS score. The 34 participants were divided into two groups; patients that had decreased CNS symptoms and decreased EDSS scores were assigned to the effect group (EG) and patients whose symptoms were not altered were treated as the non-effect group (NEG) [14].…”

Section: Patient Enrollmentmentioning

confidence: 99%

New Insights Into the Metabolic Capacity of Gut Microbiota in Coordinating the Efficacy of Mycophenolate Mofetil in Neuromyelitis Optica Spectrum Disorders

Gong

Ren

Xia

et al. 2022

Preprint

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BackgroundMycophenolate mofetil (MMF) has been widely prescribed for the therapy of neuromyelitis optica spectrum disorders (NMOSD) although not all patients display the optimal clinical response to MMF. Our study investigated a potential role of the gut microbiota in the efficacy of MMF in NMOSD patients.MethodsA total of 34 NMOSD patients treated with MMF were prospectively enrolled and grouped according to the therapeutic efficacy as effect group (EG) versus non-effect group (NEG). The gut microbiota was analyzed using 16S rRNA sequencing with stool samples and purine metabolites were profiled in serum samples from the same patients. To further decipher the role of the gut microbiota in coordinating the MMF efficacy, metabolic profiling was performed in microbiota-depleted mice. ResultsThe gut microbiota compositions could not distinguish EG and NEG patients although Clostridium and Synergistetes had significantly increased for EG and this corresponded to a significant decline in abundance of the Coprococcus genus. Additionally, purine salvage pathway (PSP) metabolites inosine, hypoxanthine, xanthine, guanine and uric acid in the serum of NMOSD patients were elevated 2 – 7-fold in the NEG group compared to EG (p< 0.05). We then used the selected PSP metabolites as indicators of MMF efficacy in a mouse model and found that the MMF response was significantly dampened when the gut microbiota was depleted by vancomycin treatment. The latter microbiomes displayed elevated levels of the PSP metabolites xanthine, inosine and hypoxanthine (p< 0.05).ConclusionsThe activity and metabolic capacities of gut microbiomes are essential for efficient response to MMF in NMOSD patients and implies an active role for the gut microbiota in coordinating host responses to MMF therapy.

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Section: Patient Enrollmentmentioning

confidence: 99%