Blood Lipopolysaccharide (LPS) Rifaximin Study

Metabolic syndrome is a condition involving elevated levels of fat in the blood, a tendency towards diabetes, hypertension, and too much fat around the abdomen (an increased waistline). Individuals with metabolic syndrome often have impaired glucose tolerance, which is a condition where blood sugar is normal when fasting (before eating), but is too high after drinking a sugary drink. This is due to an abnormality in the body's sensitivity to insulin (insulin resistance), which is due in part to an inability of the muscle to take up glucose.

People with metabolic syndrome have inflammation in their fat tissue and in their blood stream, and the changes in the level of inflammatory chemicals produced by cells in your fat tissues will be studied. One possible source of the inflammation may be the bacteria in the intestine. When individuals eat fatty foods, some of the bacterial products become attached to the fat in their blood and then get directed to fat tissue. The investigators wish to determine whether individuals have an excessive amount of inflammation in their fat tissues, and whether this inflammation comes from the bacteria in their intestines. To determine this, the investigators wish to treat individuals with an antibiotic that reduces the bacteria in their intestines and in their blood, and determine whether this reduces their overall level of inflammation.

This is a randomized, placebo-controlled proof of concept study that will examine the investigational drug Rifaximin Soluble Solid Dispersion (SSD) ability to reduce gut microbiota and thereby reduce adipose inflammation and improve insulin resistance.

Each subject enrolled will undergo a fat tolerance test with a high-fat meal, an oral glucose tolerance test, a fat biopsy, and a euglycemic clamp. Following their successful completion of those procedures subjects will be randomized to study treatment. That treatment will involve receiving the investigational drug,80 mg per day of rifaximin-soluble solid dispersion (SDD), or placebo for 12 weeks. All procedures will be performed on the Clinical Services Core of the CCTS. The initial visit will involve informed consent, and routine labs (comprehensive metabolic panel, lipid panel, TSH, CBC with platelets). These routine labs are for safety purposes and to rule out exclusionary disorders. A stool sample will also be collected and frozen for possible future analysis of bacterial microflora.

Subjects will be asked to allow the principal investigator to bank blood and tissue samples collected during this study that are not used for other study-related tests. No additional blood or tissue samples will be collected. If the subject agrees to the banking of their blood and tissue samples they will be stored in the Principal Investigator's laboratory at the University of Kentucky for an indefinite period of time or until they are used up. Stored samples will be used for future research testing to learn about how to prevent, detect, or treat insulin resistance, metabolic syndrome, diabetes or other health problems.

Each subject will undergo total body composition testing using a total body dual-energy x-ray absorptiometry (DXA) scan. The DXA scan measures the subject's bond density and body fat.

Eligibility Criteria:
Inclusion Criteria:

* Obese
* Insulin resistance or metabolic syndrome
* Body Mass Index between 27 and 45
* Waist circumference \>40" (M) or \>35" (F)
* Impaired glucose tolerance (IGT)
* Normal glucose tolerance (NGT) with at least three features of MetS
* A1C \<6.5
* Blood pressure 130/85

Exclusion Criteria:

* Pregnant or breastfeeding
* Recent or unstable cardiovascular disease
* cancer,
* Renal insufficiency (GFR\<30)
* Steroid use
* chronic inflammatory conditions
* Anticoagulant use
* Lipodystrophy
* Irritable Bowel Syndrome
* Allergy to local anesthetic
* Lactose intolerance