Manipulating the Gut Microbiome to Alleviate Steatotic Liver Disease: Current Progress and Challenges
Ernesto Saenz,
Nathally Espinosa Montagut,
Baohong Wang,
Christoph Stein-Thöringer,
Kaicen Wang,
Honglei Weng,
Matthias Ebert,
Kai Markus Schneider,
Lanjuan Li,
Andreas Teufel
Affiliations
Ernesto Saenz
Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany; Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany
Nathally Espinosa Montagut
School of Medicine, Universidad de Los Andes, Bogotá 111711, Colombia
Baohong Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Christoph Stein-Thöringer
Internal Medicine I, University Clinic Tuebingen & CoE CMFI (Controlling Microbes to Fight Infections), Tuebingen 72074, Germany
Kaicen Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Honglei Weng
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany
Matthias Ebert
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany; DKFZ Hector Cancer Institute at the University Medical Center, Mannheim 69120, Germany; Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany
Kai Markus Schneider
Department of Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
Lanjuan Li
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Andreas Teufel
Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany; Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany; Corresponding author.
The prevalence of metabolic-dysfunction-associated steatotic liver disease (MASLD) is alarmingly high; it is estimated to affect up to a quarter of the global population, making it the most common liver disorder worldwide. MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity, dyslipidemia, and insulin resistance; however, it can also manifest in lean individuals. Therefore, it is crucial to develop effective therapies for this complex condition. Currently, there are no approved medications for MASLD treatment, so there is a pressing need to investigate alternative approaches. Extensive research has characterized MASLD as a multifaceted disease, frequently linked to metabolic disorders that stem from dietary habits. Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma (HCC). In this review, we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolic-dysfunction-associated steatohepatitis (MASH), including interventions such as fecal microbiota transplantation (FMT), probiotics, prebiotics, short-chain fatty acids, antibiotics, metabolic pathway targeting, and immune checkpoint kinase blockade.
