Objective: To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance. Methods: The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored. Results: Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003). Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.