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High prevalence of lower limb atherosclerosis is linked with the gut–liver axis in patients with primary biliary cholangitis |
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| Authors: | Francesca Romana Ponziani Antonio Nesci Camilla Caputo Lucia Salvatore Anna Picca Federica Del Chierico Francesco Paroni Sterbini Emanuele Marzetti Angela Di Giorgio Luca Santoro Lorenza Putignani Antonio Gasbarrini Angelo Santoliquido Maurizio Pompili |
| Institution: | 1. Internal Medicine and Gastroenterology–Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy;2. Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy;3. Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
Department of Medicine and Surgery, LUM University, Casamassima, Italy;4. Phase 1 Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy;5. Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;6. Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital IRCCS, Rome, Italy;7. Phase 1 Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Catholic University, Rome, Italy;8. Department of Cardiovascular Sciences, Angiology and Noninvasive Vascular Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy;9. Internal Medicine and Gastroenterology–Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Department of Cardiovascular Sciences, Angiology and Noninvasive Vascular Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy |
| Abstract: | Background and AimsHypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut–liver axis and systemic inflammation.MethodsThirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota.ResultsPBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p = .01). Factors associated with LEAD at univariate analysis were VCAM-1 (p = .002), ICAM-1 (p = .003), and TNF-alpha (p = .04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0–1.1; p = .04) and TNF-alpha (OR 1.12, 95% CI 0.99–1.26; p = .04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR = 0.0008), Bifidobacterium (FDR = 0.001) and Oscillospira (FDR = 0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women.ConclusionsLEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut–liver axis. |
| Keywords: | atherosclerosis gut microbiota inflammation NAFLD PBC |