Enteral Nutrition Tolerance and the Gut Microbiome Study

Malnutrition remains highly prevalent in both acute and chronic diseases, leading to longer
hospital length of stay, greater risk of hospital readmission, and overall increase in
morbidity and mortality. Over the last few decades, studies have continued to reveal
significant clinical benefit from nutrition support, including reduction in complications and
length of stay, maintenance of gastrointestinal integrity, and overall improvement in
clinical outcomes and mortality. Despite high prevalence of Home Enteral Nutrition(HEN),
patients continue to struggle with intolerance of tube feeds leading to chronic underfeeding
and weight loss. Current guidelines recommend using standard polymeric formula or
high-protein standard formula in the hospitalized patient requiring EN and also recommend
against routine use of formulas designed to be immune-modulatory, elemental/semi-elemental,
disease-specific (diabetes), and organ-specific (hepatic, renal, pulmonary).

Blenderized Tube Feeding(BTF) offers a number of advantages to standard polymeric formula
including being able to modify the macro-nutrient and fiber content based on patient
preference. BTF use has also been increasing significantly in the past few years.

The gut microbiome, or gut host environment, consists of approximately 10 thousand cells and
has been the subject of much interest as it relates to gastrointestinal homeostasis. Our aim
therefore is to (1) characterize the structure and dynamics of complex microbial communities
using 16S rRNA- encoding gene sequences; (2) determine how they change with EN and; (3) how
they may be correlated with tolerance of EN.

A total of fifty subjects who are willing to participate in current trial and who meet
eligibility will be recruited from the Mayo Clinic HEN program. Suitable subjects will be
identified when they present at the initial HEN visit prior to undergoing enteral tube
placement.

Written informed consent will be obtained from all individuals who participate in the study.
The principal investigator or member of study team meet with each participant, review the
consent form in detail and confirm the subject's understanding of the study. The study team
will answer all questions posed by the participants and when convinced that the subject
verbally demonstrates understanding of the protocol, they will obtain a signed consent. Only
designated staff members are authorized to obtain informed consent.

At the pre-enteral tube visit, subjects will complete a gastrointestinal quality of life
(QoL) questionnaire which will form the baseline assessment for symptoms and functional
status. Body composition will be measured using Bio-impedance analysis (BIA; InBody™). A
stool specimen will be obtained for analysis of the gut microbiome at baseline. Baseline
clinical data such as current medical problems will be recorded.

Inclusion Criteria:

1. All subjects who are above 18 years of age, who present to Mayo Clinic HEN program for
initial evaluation prior to enteral tube placement

2. Require enteral nutrition support for at least 4-6 weeks from enrollment

Exclusion Criteria:

1. Patients with type 1 or 2 diabetes will be excluded due to the known pre-existing
changes in the gut microbiome in this population.

2. Patients who have had exposure to probiotics, prebiotics or antibiotics in the
preceding 4 weeks will be excluded.

3. Known allergy or intolerance to study products will be excluded.

4. Patients on parenteral nutrition will be excluded.

5. If oral feeding accounts for >25% of daily caloric intake.

6. Presence of entero-cutaneous fistula

7. Patients with short bowel syndrome will be excluded.

8. Patients who have had bariatric surgery or other alteration of GI tract will be
excluded.

9. Hematologic malignancy with absolute neutrophil count < 500/mm3

10. History of renal or liver transplant or on transplant list.