Gut microbiome, metabolome, and intestinal barrier markers correlate with disease severity in bullous pemphigoid

Although gut dysbiosis and metabolic disturbances may contribute to autoimmune skin diseases, their role in bullous pemphigoid (BP) has not been established. This study aimed to characterize the gut microbiome, metabolome, and intestinal barrier markers in BP and evaluate their associations with clinical indicators. In this case-control study, 36 patients with BP and 18 healthy controls (HCs) matched for age and sex were enrolled. Full-length 16S rRNA sequencing was conducted on fecal samples from 28 patients and 18 HCs, whereas untargeted metabolomics was conducted on samples from 24 patients and 18 HCs. Serum indicators of intestinal barrier function (lipopolysaccharide [LPS], diamine oxidase [DAO], and claudin-3 [CLDN3]) were quantified in all participants. Compared with HCs, patients with BP had lower gut microbial diversity and an altered community structure characterized by increased abundances of opportunistic pathogens and decreased abundances of anti-inflammatory and short-chain fatty acid-producing bacteria. The microbial changes were associated with clinical indices, while the Escherichia coli -to- Eubacterium hallii ( E. coli / E. hallii ) ratio demonstrated high diagnostic performance (area under the receiver operating characteristic curve = 0.913). Metabolomic analysis identified 113 differential metabolites; the associated pathway alterations correlated with bacterial abundances and clinical indices. Levels of all three intestinal barrier markers were higher in BP and were associated with disease severity and inflammation. Together, the multi-omics findings demonstrated associations with BP severity. These results indicate that changes in the gut microbiome and metabolome, alongside intestinal barrier dysfunction, are associated with BP severity and support a possible role for the gut-skin axis. Further investigation is needed to determine the utility of the E. coli / E. hallii ratio as a potential noninvasive diagnostic biomarker.