Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury
Kai Markus Schneider, Carsten Elfers, Ahmed Ghallab, Carolin V. Schneider, Eric J. C. Gálvez, Antje Mohs, Wenfang Gui, Lena Susanna Candels, Theresa H. Wirtz, Sebastian Zuehlke, Michael Spiteller, Maiju Myllys, Alain Roulet, Amirouche Ouzerdine, Benjamin Lelouvier, Konrad Kilic, Lijun Liao, Anika Nier, Eicke Latz, Ina Bergheim, Christoph A. Thaiss, Jan G. Hengstler, Till Strowig, Christian Trautwein
Abstract
BACKGROUND & AIMS: Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF. METHODS: mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF. RESULTS: inflammatory phenotype, suggesting a critical function of these cells as sensors of gut-derived signals orchestrating the inflammatory response. CONCLUSIONS: Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF.