Excess Dietary Fructose Does Not Alter Gut Microbiota or Permeability in Humans: A Randomized Controlled Pilot Study

Abstract

Background and AimsNon-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.MethodsWe performed a classical double-blind metabolic unit study in 10 obese subjects (BMI 30-40 mg/kg/m2) 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.ResultsRoutine 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.ConclusionsAlthough 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.

The interaction between the gut microbiota and dietary carbohydrates in nonalcoholic fatty liver disease

“…Diets supplemented with high-fructose corn syrup to induce NAFLD resulted in an increased Firmicutes:Bacteroidetes ratio 124,125 . However, a recent study of 10 obese patients found that fructose did not induce microbial changes 126 . Since this study used a solid form of fructose, it is possible that the small intestine efficiently prevented fructose spillover to the colon.…”

“…However, the human relevance of fructose-induced gut leakiness and microbial dysbiosis is still controversial. A recent clinical study showed that obese participants given a daily dose of 75 g of fructose over a course of a few weeks displayed no gut permeability or endotoxemia 126 . It is possible that the concentration of fructose administered in animal studies is beyond the concentrations received by typical human consumption, causing chronic and systemic changes.…”

Pathophysiological mechanisms of hypertension development induced by fructose consumption

“…Indeed, SCFAs have already been shown to protect against the progression of gut dysbiosis and hypertension. 71 However, it is important to note that median dietary fructose (74 g day −1 ) does not alter gut microbiota or permeability in humans, 72 which may be associated with the unchanged BP. [28][29][30][31][32] Fig.…”