Among individuals with primary biliary cholangitis (PBC), the altered gut microbiota plays a critical role in the occurrence and progression of the disorder, according to findings from a recently published study published in Gut Microbes and conducted in China in mice, patients with PBC and healthy controls.
In patients with the autoimmune hepatic disorder PBC, progressive, non-suppurative, destructive intrahepatic cholangitis is observed. The disease is reported mainly among women, with the prevalence varying based on geographic locale. An overall rising trend in the disorder has been described.
Although the pathogenesis and etiology of PBC remain to be elucidated, the current theory is that “PBC is caused by inappropriate immune responses (in genetically susceptible individuals) stimulated by environmental factors (microorganisms or xenobiotics), in which autoimmunity plays an important role.”
Evaluating the role of gut microbiota in PBC patients
In the current study, the researchers sought to evaluate the effect of gut microbiota derived from patients with PBC in both healthy mice and a mouse model of PBC with the use of fecal microbiota transplantation (FMT). Recognizing that the role played by gut microbiota in the occurrence of PBC, as well as the long-term effect of a dysbiotic gut microbiota on the health of patients with the disorder, remains to be elucidated, the current study transplanted feces from healthy controls or individuals with PBC into mice.
Read more about PBC therapies
To begin, the fecal microbiota from four patients with PBC (PBC-FMT) or from three healthy controls (HC-FMT) was transplanted into pseudo germ-free mice or into 2-octynoic acid–bovine serum albumin (2OA-BSA)-induced models of PBC. Analyses were performed on the functions, histology, and transcriptome of the liver, as well as on the microbiota and metabolome of the feces.
In a second analysis, the liver transcriptomes of seven patients with PBC and seven normal individuals were compared. In a third analysis, the liver transcriptomes of patients with other hepatic disorders were obtained from online databases, and then compared with the data derived from humans and mice.
Gut microbiota may be key in improving PBC outcomes
Results of the study showed that PBC-FMT increased serum alkaline phosphatase levels, total bile acid content, hepatic injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice. In addition, PBC-FMT increased the serum glycylproline dipeptidyl aminopeptidase concentration and hepatic damage in a 2OA-BSA–generated PBC mouse model.
The authors reported the gut microbiota and metabolome differed between PBC-FMT and HC-FMT, mirroring those of their donors. In fact, following FMT, the gut microbiota of mice reflected key differentially abundant bacteria between human fecal donors. PBC-FMT had a tendency to upregulate liver immune and signal transduction pathways, but to downregulate metabolic pathways, as observed in some individuals with PBC.
The hematopoietic cell lineage, Toll-like receptor, and peroxisome proliferator–activated receptor signaling pathway were not impacted in individuals with alcoholic hepatitis, hepatitis B virus, hepatic C virus (HCV), HCV cirrhosis, or nonalcoholic steatohepatitis, thus revealing their potential roles in the gut microbiota that affect PBC.
“The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment,” the authors concluded.
