Intestinal barrier breakdown and mucosal microbiota disturbance in neuromyelitis optical spectrum disorder

Abstract Background and purpose The mechanism underlying the pathology of neuromyelitis optica spectrum disorder (NMOSD) remains unclear even though increased expression of the water channel protein aquaporin-4 (AQP4) on astrocytes plays an important role. Our previous study revealed that dysbiosis was detected in the faecal microbiota of NMOSD patients. In this study, we further investigated whether the intestinal barrier and mucosal flora balance were also interrupted in NMOSD patients. Methods Sigmoid mucosal biopsies were collected via endoscopy from six patients with NMOSD and compared with those from three patients with multiple sclerosis (MS) and five healthy controls (HCs). These samples were processed for electron microscopy and immunohistochemistry to investigate changes in ultrastructure and in the number and size of intestinal inflammatory cells. Changes in mucosal flora were also analysed by high-throughput 16S ribosomal RNA gene amplicon sequencing. Results The intercellular space between epithelia of the colonic mucosa became wider in MS and NMOSD patients compared to the HCs (P < 0.01), and the expression of tight junction proteins in MS and NMOSD patients significantly decreased compared to that in the HCs. Activation of microphages with many inclusions inside the cytoplasm and enlarged plasmocytes with more particles were found in the NMOSD group. Quantitative analysis showed that the percentage of small-size CD 38 + and CD138 + cells was lower but that of larger-size cells became higher in NMOSD patients, and 16S data showed that the abundance of Streptococcus and Granulicatella was dramatically increased in NMOSD patients. Conclusions NMOSD patients exhibited a disrupted intestinal barrier and intestinal dysbiosis and activation of intestinal inflammation, which suggested a potential pathophysiological mechanism of NMOSD underlying intestinal inflammation.