Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study
Condition: Non-Alcoholic Fatty Liver Disease; Obesity
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional

Summary: 
      Non alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function
      tests in the U.S. (Browning, et al., 2004), ranging from steatosis to end-stage liver
      disease. Fructose ingestion by the American public has steadily increased since the 1980's,
      and with it increases in NAFLD, fatty liver hepatitis (NASH), diabetes, obesity, and
      cardiovascular disease. Foods and beverage in the U.S. are typically sweetened with sucrose
      (50% glucose and 50% fructose) or high fructose corn syrup (45-58% glucose and 42-55%
      fructose) (Stanhope, et al., 2009). Research into the role that added fructose plays in the
      emerging chronic health issues is necessary to affect public policy and provide the
      connection between fructose and the increasing incidence of these co-morbidities.

      There is evidence that gut bacteria contribute to a range of human diseases including those
      of the liver and gastrointestinal tract. Dietary fructose has been suggested to play a role
      in the development of these diseases and has been shown to alter gut microbes in animals. If
      the investigators find that dietary fructose alters bacteria in the human gut, this would
      suggest a potential targetable link between high fructose diet and disease.
    

Detailed description: 
      Non- alcoholic fatty liver disease (NAFLD) occurs in 30% of the adult US population (Luther,
      J., et al., 2015). Eating large amounts of fructose (a dietary sugar) increases liver fat
      accumulation and worsens NAFLD. In addition, fructose consumption has been shown to greatly
      increase triglycerides(fat) in the blood after meals, increasing the risk of heart
      disease,(Stanhope,et al., 2009) insulin resistance and diabetes. Current theories on liver
      disease caused by consuming fructose focuses on changes in the breakdown of fat by the liver.
      In experimental animals, fructose feeding changes the bacteria population (microbiota) in the
      gut, causes NAFLD and NASH, and increases leaking of toxins from the intestine (intestinal
      permeability) to the blood stream resulting in inflammation.

      In humans, fructose consumption rapidly increases liver fat. However, changes in gut
      microbiota have not been studied. The proposed study will compare the addition of fructose or
      glucose to the study subjects' usual diet in a crossover design. They will not know which
      sugar they are receiving.

      The Investigators plan to study postmenopausal, moderately obese but healthy women, and
      moderately obese but healthy men (age 45-70 years) to find out the effect of fructose verses
      glucose on the bacteria in their stool and inflammation in the bowel. The Investigators
      hypothesize that adding fructose to the participant's usual diet, compared to glucose, will
      change stool bacteria composition and the products that the bacteria produce, which may
      increase intestinal leakage, and increase markers of inflammation in the stool and blood due
      to this leakage. These changes may contribute to fructose -induced liver disease.
    

Intervention name(s): Fructose Solution (75 Grams); Glucose Solution (75 grams)
Intervention type(s): Other; Other
Intervention description(s): Fructose given in divided doses at breakfast and dinner.; Glucose given in divided doses at breakfast and dinner.
Other intervention name(s): Dextrose
Intervention MeSH terms: Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: obesity; fructose; glucose; fecal microbiota; intestinal permiability; fecal metabolites