Gut microbiome and fecal metabolic alteration in systemic lupus erythematosus patients with depression
Han Yao, Hao Yang, Yueying Wang, Qian Xing, Yan Lin, Yaru Chai
Abstract
Background Mental health disorders in systemic lupus erythematosus (SLE) are gradually getting recognized; however, less is known regarding the actual structure and compositional alterations in gut microbiome and metabolism and the mechanisms of how they affect depression development in SLE patients. Methods Twenty-one SLE patients with depression (SLE-d), 17 SLE patients without depression (SLE-nd), and 32 healthy controls (HC) were included in this study. Fecal samples were collected for 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics. Results The structure of gut microbiome in the SLE-d group changed compared with that in the other two groups. The microbiome composition of SLE-d group showed decreased species richness indices, characterized by low ACE and Chao1 indices, a decrease in the ratio of phylum Firmicutes to Bacteroidetes, genus Faecalibacterium and Roseburia . A downregulation of the metabolite fexofenadine involved in bile secretion was positively correlated with the genus Faecalibacterium , Subdoligranulum and Agathobacter . Compared with the SLE-nd group, the SLE-d group had elevated serum levels of IL-2 and IL-6 and decreased BDNF. Interestingly, abundance of the genus Faecalibacterium and Roseburia was negatively correlated with IL-6, abundance of the genus Roseburia was negatively correlated with IL-2, and abundance of the genus Bacteroides was positively correlated with IL-2. Conclusion This study identified specific fecal microbes and their metabolites that may participate in the development of SLE-d. Our findings provide a new perspective for improving depression in SLE patients by regulating the gut–brain axis.