Journal
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume 47, Issue 2, Pages 192-202Publisher
WILEY
DOI: 10.1111/apt.14397
Keywords
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Funding
- Norgine
- Wellcome Trust Grant
- National Institute for Health Research [PB-PG-0215-36070] Funding Source: researchfish
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Background: Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. Aim: To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. Methods: We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Results: Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Conclusions: Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of healthy bacteria may ameliorate the dysbiosis and alter prognosis.
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