Gut Microbiota Dysbiosis Characterized by Abnormal Elevation of Lactobacillus in Patients with Immune- mediated Necrotizing Myopathy

Abstract

Abstract Aim: The gutmicrobiotaplays an important role in human health. In this study, we aimedto investigate whether and whereby the gut microbiota communities are alteredin patients with immuno-mediated necrotizing myopathy (IMNM) and to provide new ideas for further exploring the pathogenesis of IMNM or screening its clinical therapeutic targets in the future. Methods: The gut microbiota in 42 fecal samples collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta diversity analyseswere applied to examine the bacterial diversity and community structure between the IMNM and HC groups. Welch’s t test was performed to identify the significantly abundant taxa (phylum and genera) of bacteria between the two groups. Linear discriminant analysis (LDA) effect size (LefSe) analysis was applied to detect the most discriminatory taxa between the two groups. Spearman correlation analysis was performed to analyze the correlation between the gut microbiota and clinical indicators and the correlation network between the genera. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P <0.05 was considered to be statistically significant. Results: The diversity of the gut microbiota of IMNM patients differed from that of healthy people and decreased obviously based on principal coordinate analysis (PCoA)and Chao1, Shannon and Simpson indexes (p<0.05). Analysis of the composition and abundance distribution of gut microbiota showed thatin IMNM patients, the relative abundances of Bacteroides, Roseburiaand Coprococcus were decreased compared to thosein the HC group, while the relative abundancesof Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, the relative abundance of Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies and anti-Ro52 antibodies and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, we constructed a prediction model using thetop five differential genera to distinguish IMNM patients from healthy individuals, which was verified using an ROC curve (area under curve: 87%, 95% confidence interval: 73–100%). Conclusion: We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and iscorrelated with systemic autoimmune features.