Alteration of Gut Microbiota in Primary Biliary Cholangitis Patients with Non-Response to Ursodeoxycholic Acid

Abstract

Objective: A close relationship between the structure of gut microbiota and the development of primary biliary cholangitis (PBC) has been revealed in previous studies. This study aims to reveal the components and metabolic pathways of gut microbiota associated with the non-response to ursodeoxycholic acid (UDCA) of PBC patients. Methods: Fecal samples were collected from PBC patients before receiving UDCA (n = 8, PBC group), PBC patients with response to UDCA (n = 8, Resp group) and PBC patients with non-response to UDCA (n = 8, Non-Resp group). The 16S ribosomal RNA (rRNA) gene was sequenced to analyze the gut microbiota in feces. Subsequently, the relative abundance, alpha and beta diversity of gut microbiota, and the correlation between the abundance and clinical characteristics in the samples from the three groups were analyzed to construct a correlation network of gut microbiota. Results: The diversity and richness of gut microbiota were significantly decreased in PBC patients in the Non-Resp group, which were significantly different from the PBC and Resp groups. The gut microbiota with the top 10 expressed abundances that exhibited differences and linear discriminant analysis (LDA) scored greater than 4. The abundance of Fusobacteria expression in the gut significantly increased in PBC patients in the Non-Resp group, while that of Ruminococcaceae and Verrucomicrobia expressions decreased. Conclusions: The decrease of gut microbial diversity and richness in PBC patients with non-response to UDCA may be linked to the abnormal abundance and related metabolic pathways of gut microbiota such Fusobacteria, Ruminococcaceae, and Verrucomicrobia. Gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC patients with non-response to UDCA.