<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition"^^ . "Having reached an epidemic magnitude, obesity has experienced a drastic increase in prevalence over the \r\npast decades. Together with obesity, associated pathologies, including metabolic syndrome, became \r\nmore common, which further increase the risk of long-term complications. As such, chronic manifestation \r\nof these conditions frequently leads to metabolic dysfunction-associated steatohepatitis (MASH). MASH \r\nhas gained significantly in importance due to the lack of treatment options and the progression towards \r\nfibrosis and hepatocellular carcinoma (HCC), making it the fastest-growing cause of primary liver cancer. \r\nThe intestinal microbiota is known to be influenced by a variety of metabolic diseases and to actively \r\ncontribute to inflammatory events. Indications for a role of the microbiota in chronic liver diseases exist, \r\nbut if and how intestinal bacteria drive the progression of MASH towards HCC remains uncertain.\r\nTo investigate the role of the microbiota in choline-deficient high fat diet (CD-HFD)-induced MASH and \r\nHCC I depleted intestinal bacteria using a broad-spectrum antibiotics (ABx) cocktail. To decipher the effect \r\nof microbiota depletion on different stages of pathogenesis, I performed ABx treatment either \r\nprophylactically or therapeutically after disease onset. I analyzed the effect of microbiota depletion on \r\nMASH and HCC pathogenesis by characterizing immunological, transcriptional and metabolic signatures \r\nin the mice. To evaluate the effects of CD-HFD feeding and the ABx treatment on intestinal bacteria, I \r\ndetermined the microbiota composition by shotgun metagenomic sequencing.\r\nMy data confirmed that the CD-HFD MASH model can recapitulate previously described mechanisms \r\ninvolving the gut-liver axis and that ABx-mediated microbiota depletion reduces MASH development. \r\nMoreover, I was able to show that ABx treatment limits MASH-to-HCC transition in CD-HFD mice by \r\npreventing fibrosis development, which resulted in a lower liver tumor incidence. In addition, prophylactic \r\nABx treatment modified certain tumor characteristics, which were possibly linked to an increased tumor \r\nsize observed in these mice. Therapeutic ABx treatment reversed this effect, indicating an ambivalent role \r\nof microbial presence at different stages of the pathogenesis. Furthermore, I found diminished IgA-dependent activation of FCGR1-expressing myeloid cells as the likely cause of ABx-mediated reduced \r\nfibrogenesis, which was presumably supported by a variety of metabolic and transcriptional changes upon \r\nABx treatment with additional beneficial effects on MASH-to-HCC transition.\r\nAlthough further research is needed to understand the spectrum of underlying mechanisms, my study \r\nconfirms the detrimental contributions of intestinal bacteria to the MASH-to-HCC transition and suggests \r\nan ambivalent role of bacteria depending on the disease stage."^^ . "2025" . . . . . . . "Svenja"^^ . "Schühle"^^ . "Svenja Schühle"^^ . . . . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (PDF)"^^ . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (Other)"^^ . . . . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (Other)"^^ . . . . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (Other)"^^ . . . . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (Other)"^^ . . . . . . "Deciphering the role of the gut microbiota in\r\nmurine MASH and MASH-to-HCC transition (Other)"^^ . . . . . "HTML Summary of #34638 \n\nDeciphering the role of the gut microbiota in \nmurine MASH and MASH-to-HCC transition\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .