Alterations of fecal microbiome and metabolome in pemphigus patients

The role of gut microbiome and metabolic substances in the development of autoimmune diseases has gradually been revealed. However, the relevant gut features in pemphigus have not been well clarified. We collected stool samples from pemphigus patients and healthy controls (HCs). Metagenomic sequencing and liquid chromatography-mass spectrometry (LC/MS) metabolome sequencing were performed to analyze the compositional and metabolic alternations of the gut microbiome in pemphigus patients and HCs. We observed the reduced richness and diversity and greater heterogeneity in pemphigus patients, which was characterized by a significant decrease in Firmicutes and an increase in Proteobacteria. At the species level, Intestinal pathogenic bacteria such as Escherichia coli and Bacteroides fragilis were significantly enriched, while anti-inflammatory bacteria and butyric acid-producing bacteria were significantly reduced, which were related to clinical indicators (Dsg1/3 and PDAI). 4 species were selected by the machine learning algorithm to better distinguish pemphigus patients from healthy people. Metabolomic analysis showed that the composition of pemphigus patients was different from that of HCs. PE (18:3 (6Z,9Z, 12Z)/14:1 (9Z)) was the main metabolic substance in pemphigus and involved in a variety of metabolic pathways. While Retinol, flavonoid compounds and various amino acids decreased significantly compared with HCs. Furthermore, we found that differences in the levels of these metabolites correlated with changes in the abundance of specific species. Our study provides a comprehensive picture of gut microbiota and metabolites in pemphigus patients and suggests a potential mechanism of the aberrant gut microbiota and metabolites in the pathogenesis of pemphigus.