Effects of high-dose glucocorticoids on gut microbiota in the treatment of Graves’ ophthalmopathy

Many studies indicate the gut microbiome is associated with diseases caused by administering high-dose glucocorticoids (GCs), such as hypertension, hyperglycemia, and osteoporosis. However, the association between intestinal flora and the use of high-dose GCs remains elusive. We aimed to characterize gut microbiome in Graves' ophthalmopathy (GO) patients after administering high-dose GCs. In this study, 20 primary GO patients were recruited. The differences in gut microbiota of GO patients before and after administering high-dose GCs were analyzed by 16S rDNA sequencing technology. Untargeted metabolomic analysis was used to examine the differences in gut metabolites between two groups. There were significant differences in α and β diversities of gut microbiota in GO patients before and after administering high-dose GCs. The random forest analysis indicated that three intestinal bacteria (<i>Faecalibacterium, Streptococcus,</i> and <i>Prevotella</i>) could distinguish the two groups with the highest accuracy, which was proven by receiver operator characteristic curve and linear discriminant analysis effect size analysis. The short-chain fatty acid-producing ability in GO patients' gut after high-dose GC administration was significantly decreased. The 5-hydroxytryptamine levels significantly increased in the gut of GO patients after administering high-dose GCs. Our study suggests that high-dose GC administration causes the changes in gut microbiome and metabolites. Moreover, the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.IMPORTANCEFor the first time, we revealed that gut microbiome and metabolome in Graves' ophthalmopathy patients after high-dose glucocorticoid (GC) administration significantly changed, and the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.