College of Public Health and Human Sciences

• Excess dietary energy provokes gut dysbiosis leading to increased inflammation.
• Impairments in gut function contribute to metabolic endotoxemia.
• Endotoxemia depletes vitamin C, which in turn impairs vitamin E trafficking.
• Higher vitamin C intake can restore gut-liver functions and antioxidant status

Metabolic syndrome (MetS) is a constellation of cardiometabolic risk factors, which together predict increased risk of more serious chronic diseases. We propose that one consequence of dietary overnutrition is increased abundance of Gram-negative bacteria in the gut that cause increased inflammation, impaired gut function, and endotoxemia that further dysregulate the already compromised antioxidant vitamin status in MetS. This discussion is timely because “healthy” individuals are no longer the societal norm and specialized dietary requirements are needed for the growing prevalence of MetS. Further, these lines of evidence provide the foundational basis for investigation that poor vitamin C status promotes endotoxemia, leading to metabolic dysfunction that impairs vitamin E trafficking through a mechanism involving the gut-liver axis. This report will establish a critical need for translational research aimed at validating therapeutic approaches to manage endotoxemia—an early, but inflammation-inducing phenomenon, which not only occurs in MetS, but is also prognostic of more advanced metabolic disorders including type 2 diabetes mellitus, as well as the increasing severity of nonalcoholic fatty liver diseases.