IMPORTANCE OF A 2×2 FACTORIAL EXPERIMENTAL DESIGN IN ASSESSING THE INTERACTION OF A HIGH-FAT DIET AND ANTIBIOTIC THERAPY ON THE GUT–LIVER AXIS

Abstract

Fatty liver disease is a complex process accompanied by simultaneous changes in metabolic factors, the gut microbiota, and the immune-inflammatory response. While a high-fat diet promotes triglyceride accumulation in hepatocytes, antibiotics rapidly alter the composition and metabolic activity of the gut microbiota. However, the final direction of the antibiotic effect is not always the same: under some conditions, a reduction in the microbial load may alleviate endotoxemia and steatosis, whereas in other situations, persistent dysbiosis may weaken the epithelial barrier and aggravate hepatic inflammation. Therefore, comparison of intact animals only with a “high-fat diet + antibiotic” group makes it difficult to determine which factor is predominant. An experimental design that separates the effects of diet, antibiotic therapy, and their interaction is necessary for an objective assessment of gut–liver relationships.