The influence of perilipin 5 deficiency on gut microbiome profiles in murine metabolic dysfunction-associated fatty liver disease (MAFLD) and MAFLD-hepatocellular carcinoma.

Abstract

INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency inreduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer. METHODS: Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and-deficient () mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples. RESULTS: Notably, we discovered that the absence ofalone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly,animals exhibited an enrichment of the beneficial taxain both animal models. DISCUSSION: Our findings identifyas a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC.