Gut barrier dysfunctions and alcohol-associated liver disease in humans : old partners in crime
(2022)
Files
LucaMaccioniPhDThesisFINAL.pdf
Open Access - Adobe PDF
- 94.27 MB
Details
- Authors
- Supervisors
- Starkel, Peter
- Abstract
- Chronic alcohol consumption is one of the leading causes of chronic liver disease and liver-related deaths worldwide. Only up to 20% of patients with an alcohol use disorder (AUD) progress to advanced stages of alcohol-associated liver disease (ALD) from the benign form of the disease, namely simple steatosis. This process is usually silent at early disease stages and the mechanisms underlying disease progression are yet incompletely understood. Recent reports have highlighted the role of the gut-liver axis in ALD. However, data in early human ALD were scarce. Therefore, this PhD work aimed at investigating dysfunctions of the intestinal barrier in AUD patients and their relationship with activation of immune responses contributing to ALD progression. We here revealed a specific diminution of effector immune cells in the duodenal mucosa and the presence of a tolerogenic immune status associated with changes in the gut microbiota and elevated translocation of microbial products in patients with progressive ALD. These microbial products activated circulating monocytes and liver inflammatory responses, thus contributing to systemic inflammation and ALD progression. The results of this PhD thesis support the contribution of gut barrier dysfunctions in human ALD pathogenesis.
- Affiliations
Citations
Maccioni, L. (2022). Gut barrier dysfunctions and alcohol-associated liver disease in humans : old partners in crime. https://hdl.handle.net/2078.5/104880