Starch-entrapped Microspheres [Nutrabiotix Fiber] for Gut Health

The long-term objective of our research program is to show that targeted colonic delivery of
natural specific fermentable carbohydrates will maintain and promote gut health by changing
the gut microbiota [prebiotic effect], by increasing "protective and growth promoting"
factors such as butyrate, and enhancing intestinal barrier function. These health-promoting
functions may prevent and treat a wide range of disorders associated with an abnormal
microbiota (dysbiosis) and/or disrupted gut barrier function. Examples of disorders
associated with dysbiosis and disrupted gut barrier (leaky gut) are allergic disorders,
inflammatory bowel disease, diverticular disease, colon polyps and cancer, alcoholic liver
disease, non-alcoholic steatohepatitis (NASH- the most common liver disease in the USA), and
irritable bowel syndrome (IBS, the most common GI illness in the US with a high loss of
productivity and a high rate of utilization of health care resources).

Nutrabiotix fiber is a prebiotic and is able to promote gut health through changes in the
stool microbiota composition favoring saccharolytic bacteria like Bifidobacteria and
diminishing proteolytic bacteria like Clostridia. This change in the intestinal microbiota
composition should result in increases in the products of carbohydrate fermentation [SCFA]
and decreases in the products of protein breakdown [indoles and phenols] in the stool. Also,
the fiber is well tolerated and without side effects and is an effective fiber that increases
stool bulk and regulates bowel movement.

Inclusion Criteria:

- Healthy, asymptomatic 18 to 65 years subjects with BMI 20-30 and self described
unsatisfactory bowel habit

Exclusion Criteria:

1. Abnormalities in CBC (Hgb <12 g/dL, platelet count <100 000, WBC <4000 or >10 000);

2. Abnormal liver function tests (ALT, AST, alkaline phosphatase, or bilirubin >1.5 times
normal range);

3. Abnormal renal function tests (BUN or creatinine >1.5 times normal range);

4. Low serum albumin (<3 g/dL);

5) Abnormal TSH level;

(6) High CRP;

(7) Significant GI symptoms (except for constipation or occasional rectal bleeding due to
hemorrhoids);

(8) Prior intestinal resection;

(9) Patient history of GI diseases [except for hemorrhoids or occasional (<3 times a week)
heartburn];

(10) Antibiotic use within last 12 weeks prior to enrollment;

(11) Lean (BMI <25) or obese (BMI>30) subjects because obesity could be associated with
abnormal microbiota;

(12) Significant cardiac or respiratory diseases (defined by requiring daily medication for
management of their diseases);

(13) Severe hypertension (defined as uncontrolled hypertension in spite of therapy, or
requirement of more than one medication to treat hypertension; well-controlled, mild
hypertension may be included);

(14) Insulin-requiring and/or poorly controlled diabetes (well-controlled diabetics with
HbA1c <6 may be enrolled);

(15) Significant psychological disorders;

(16) Drug and/or alcohol abuse;

(17) Unwillingness to consent to the study;

(18) Plan to have a major change of the dietary habit during the following 5 months;

(19) Subjects younger than 18 or older than 65. Older subjects are excluded in this initial
study because of high co-morbidity in older subjects. Children are excluded for this
initial Phase I study where the safety is not established;

(20) Pregnant and lactating women due to lack of information about safety of the product in
pregnant and lactating women.