Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies

Abstract

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.

Comorbidities and Malignancy among NAFLD Patients Compared to the General Population, A Nation-Based Study

“…In the last few years, increased interest and knowledge regarding the pathophysiology of NAFLD, the role of the microbiome, and NAFLD-associated diseases such as diabetes mellitus have come to light. Multiple factors (environmental, genetic, and comorbidities) have been shown to modify the gut microbiota [ 24 , 25 , 26 ]. Other studies have demonstrated a correlation between a specific microbial signature and the severity of NAFLD and the prediction of NAFLD-related cirrhosis [ 27 , 28 , 29 ].…”

Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment

“…Clinical investigations have included a wide range of novel therapeutic targets and prospective medications for the treatment of obesity and MAFLD; however, the results and efficacy have not yet been validated. [207][208][209][210] Glucagon-like peptide-1 (GLP-1)is an incretin hormone that originates from the gut. Additionally, it reduces caloric intake and stomach emptying while increasing insulin release through beta cells.…”

Effect of Nut Consumption on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

“…Nonalcoholic fatty liver disease (NAFLD) is a significant public health concern and is the primary cause of chronic liver disease. NAFLD is a liver manifestation of metabolic syndrome and is prevalent in obese and diabetic patients [ 1 ]. With the rising incidence of obesity and diabetes worldwide, NAFLD is becoming increasingly prevalent.…”