Work

Excess dietary fructose does not alter gut microbiota or permeability in humans: A pilot randomized controlled study

Year: 2021

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: ABSTRACT Background and Aims Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD due in part to a consequence of impaired hepatic fructose metabolism. Pre-clinical data have emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to explore the relevance of these pre-clinical studies to observations in humans. Methods We performed a classical double-blind metabolic unit study in 10 obese subjects (BMI 30-40 mg/kg/m 2 ) providing 75gms. of either fructose or glucose in their individual diets substituted isocalorically for complex carbohydrates in a cross-over study. Excess fructose intake was provided in the fructose arm of the study and totaled a mean of 22.7% of calories. Results Routine blood, uric acid, liver function and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia ), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation and plasma metabolites were essentially unchanged by either intervention. Conclusions Although pre-clinical rodent studies have shown that excess fructose causes pronounced changes in the gut microbiome, metabolome, and permeability as well as endotoxemia, this did not occur in obese individuals fed fructose in amounts known to enhance NAFLD. Therapeutic efforts to improve NAFLD through changes in the gut microbiome and gut homeostasis may not be beneficial.

Source: Journal of Clinical and Translational Science

DOI: 10.1017/cts.2021.801