Probiotic Lactobacillus rhamnosus mitigates PBC-like features in Mcpip1-deficient mice via modulation of gut-liver crosstalk.
Publisher DOI
PubMed ID
41846103
Abstract
Background
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive biliary destruction and cholestasis. Current therapies, including ursodeoxycholic acid (UDCA), exhibit limited efficacy in advanced disease. In this study, we investigate the therapeutic potential of microbial intervention using Lactobacillus rhamnosus (Lbr) in the Mcpip1fl/flAlbCre knockout mouse model of PBC, which we described previously. Knockout mice develop human PBC-like features such as bile acid dysregulation, autoantibodies, cholangiocyte hyperplasia and fibrosis.
Methods
Six-week-old Mcpip1fl/fl (wild-type) and Mcpip1fl/flAlbCre (knockout) mice were treated with Lactobacillus rhamnosus supplementation, UDCA (15 mg/kg/day), UDCA + Lbr, and UDCA + OCA (obeticholic acid, 10 mg/kg/day) for six weeks. Treatment response was characterized by liver and gut pathology, serum biomarkers, transcriptomic profiles, and microbiome composition.
Results
Treatment of Mcpip1fl/flAlbCre animals with Lbr decreased serum bile acids and reduced pathological cholangiocyte dysplasia in the liver, decreased leukocyte infiltration and fibrosis. RNAseq of liver tissue revealed enrichment of humoral immune responses and T cell activation pathways in knockouts, all of which were significantly attenuated by Lbr monotherapy. Gut pathology marked by increased intraepithelial lymphocyte infiltration and mucosal hypertrophy, was also normalized upon Lbr administration. Finally, probiotic treatment modulated the microbiome by increasing the Firmicutes/Bacteroidetes ratio and enriching butyrate-producing Lachnospiraceae. Administration of UDCA and UDCA+OCA had less pronounced effects: only decreased serum bile acids was detected in both groups.
Conclusions
Probiotic intervention with Lbr represents a feasible strategy to attenuate fibrotic progression in a mouse model of autoimmune cholestatic disease by modulation of the gut-microbiome-immune crosstalk.
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive biliary destruction and cholestasis. Current therapies, including ursodeoxycholic acid (UDCA), exhibit limited efficacy in advanced disease. In this study, we investigate the therapeutic potential of microbial intervention using Lactobacillus rhamnosus (Lbr) in the Mcpip1fl/flAlbCre knockout mouse model of PBC, which we described previously. Knockout mice develop human PBC-like features such as bile acid dysregulation, autoantibodies, cholangiocyte hyperplasia and fibrosis.
Methods
Six-week-old Mcpip1fl/fl (wild-type) and Mcpip1fl/flAlbCre (knockout) mice were treated with Lactobacillus rhamnosus supplementation, UDCA (15 mg/kg/day), UDCA + Lbr, and UDCA + OCA (obeticholic acid, 10 mg/kg/day) for six weeks. Treatment response was characterized by liver and gut pathology, serum biomarkers, transcriptomic profiles, and microbiome composition.
Results
Treatment of Mcpip1fl/flAlbCre animals with Lbr decreased serum bile acids and reduced pathological cholangiocyte dysplasia in the liver, decreased leukocyte infiltration and fibrosis. RNAseq of liver tissue revealed enrichment of humoral immune responses and T cell activation pathways in knockouts, all of which were significantly attenuated by Lbr monotherapy. Gut pathology marked by increased intraepithelial lymphocyte infiltration and mucosal hypertrophy, was also normalized upon Lbr administration. Finally, probiotic treatment modulated the microbiome by increasing the Firmicutes/Bacteroidetes ratio and enriching butyrate-producing Lachnospiraceae. Administration of UDCA and UDCA+OCA had less pronounced effects: only decreased serum bile acids was detected in both groups.
Conclusions
Probiotic intervention with Lbr represents a feasible strategy to attenuate fibrotic progression in a mouse model of autoimmune cholestatic disease by modulation of the gut-microbiome-immune crosstalk.
Date Issued
2026-06
Publication Type
Article
Subject(s)
Subjects
Gut-liver axis
•
Lactobacillus rhamnosus
•
Liver
•
Mcpip1 knockout
•
Microbiome
•
Primary biliary cholangitis
Language(s)
en
Author(s)
Trzos, Katarzyna | |
Hutsch, Tomasz | |
Koval, Anastasiia | |
Śmierciak, Danuta | |
Machaj, Gabriela | |
Molano, Leidy-Alejandra G | |
Rehner, Jacqueline | |
Rahman, Md Mobashir | |
Förster, Maximilian Olaf | |
Bednarek, Marcin | |
Pilarczyk-Zurek, Magdalena | |
Surma, Szymon | |
Koziel, Joanna | |
Krawczyk, Marcin | |
Becker, Soeren L | |
Ylla, Guillem | |
Jura, Jolanta | |
Kotlinowski, Jerzy |
Journal
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier
ISSN
1879-260X
0925-4439
Access(Rights)
open.access