Liver_Microbiome_Intervention

Non-alcoholic fatty liver disease (NAFLD) has been largely assessed within the context of overnutrition. Undernutrition, however, may also trigger hepatic steatosis and shape metabolomic health trajectories. Undernutrition remains a major health concern and is affected by fecal contamination. We report that the MBG model, which combines protein/fat-deficient diet and early-life fecal microbial exposures, exhibits NAFLD-like pathology. To examine the influence of diet and gut microbes on NAFLD we conducted a set of dietary reversals and profiled the microbiome in the following conditions: CON = healthy model, MBG = malnutrition model, C-MBG = adult-onset malnutrition, and MBG-R = malnourished model reversed on a healthy diet. In contrast to MBG mice, C-MBG mice do not display fatty liver features suggesting a critical developmental window where diet and microbes shape liver function. Moreover, this work demonstrated that dietary intervention largely reverses aberrant fatty liver features and microbiome shifts reported in early-life malnutrition models.