Variability in Microbial Response to Dietary Fiber (TRIUMPH)

The goal of this clinical trial is to understand varying in responses to different dietary patterns in healthy people who are getting a health screening colonoscopy.

The main questions it aims to answer are:

• What is the variability in the change of the microbes in the gut of (1) a provided diet that is high in fiber vs (2) a diet of the participant's choice.
• What is the magnitude of fasting changes in glucose and lipids following the short-term, high-fiber feeding period and identify candidate predictive factors (short-chain fatty acids, BMI, sex, starting glucose level) for these changes

Participants will be in one of two groups:

1. High-fiber diet group: These participants will have a series of measurements that include: blood biochemistries, body composition measured via DEXA, anthropometrics, surveys and questionnaires, and collection of fecal samples.
2. Normal diet group: These participants will eat a diet that is of their choosing (ad libitum) and will have a series of measurements that include: fecal samples, and questionnaires/surveys including food records.

Study Overview

• Status: Completed
• Conditions: Microbial Colonization
• Intervention / Treatment: Dietary supplement: High fiber

Detailed Description

Fiber fermentation in the colon produces short chain fatty acids (SCFA) and alters the microbial composition and activity. These effects may be mechanisms linking a high-fiber diet to improved health. However, different people may respond to dietary fiber differently and the variability in early, dietary-induced SCFA concentration changes has not been established. This lack of basic understanding in individual patterns of microbial SCFA production significantly limits efforts in the field of Precision Nutrition designed to target dietary strategies to improve health and advance lifestyle treatments in healthcare in the future. In this project, the central hypothesis is that the mechanisms by which dietary fiber provide metabolic benefits include a direct physical effect to improve fasting glucose and lipids and an effect related to increasing SCFA concentration. These are the ideas being tested in this study.

Using fiber derived from peas in a two-week human feeding intervention, Aim 1 will quantitate the variability in high-fiber-induced change in microbial composition and SCFA production by specifically testing the hypothesis that Following successful colonoscopy bowel prep, variability in the reduction in microbial species will be very small, while repopulation after a standardized high-fiber diet will be characterized by larger differences between individuals with regard to the quantity of bifidobacterial and the Firmicutes/ Bacteroidetes ratio.

Aim 2 will quantitate the magnitude of fasting changes in glucose and lipids following the short-term, high-fiber feeding period and identify candidate predictive factors (SCFA, BMI, sex, starting glucose level) for these changes by testing the hypothesis that a two-week, high-fiber diet will result in lower plasma glycemia and triglycerides. Participants (n=30) who have undergone a health-screening colonoscopy (HSC) are fed a high-fiber diet for 14 days. Fecal samples are collected before the colonoscopy and on days 1, 7 and 14 after the colonoscopy during high-fiber feeding. On day 1 and 14, the subject visits the clinical unit for a fasting blood draw (for measurement of glucose, lipids, and plasma SCFA), surveys and questionnaires.

A control arm will also be included as part of this study. The purpose of the control arm is to quantitate the variability in microbial composition and SCFA production from an ad libitum diet of participants. Instead of providing a high-fiber diet, the repopulation of the gut microbiome will be observed when participants eat a diet that is of their choosing. A series of food records and fecal samples pre- and post-procedure will be collected. Figure 2 shows the protocol of this arm. Food records will be collected: pre-procedure, days 0 (procedure day), 1, 2, 4, 7, 10, 13. Fecal collection will be collected: pre-procedure, 3, 5, 8, 11, 14. This arm will not include the blood collection or DEXA scan.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Intervention Arm

Inclusion Criteria:

• Men and women
• Age 45-65y: the average age of people referred for a screening colonoscopy
• BMI ≥20.0 or ≤40.0 kg/m2
• Weight stable: no fluctuations in body weight of greater than 4 kg in the last 3 months
• Scheduled for a health-screening colonoscopy
• Willingness to consume a high-fiber diet
• Willing to provide blood and fecal samples

• Healthy or have one or more characteristics of the metabolic syndrome (but not diabetic) Metabolic syndrome criteria

  1. A large waistline: 35 inches or more for women 40 inches or more for men
  2. High triglycerides: 150 mg/dL or higher
  3. Low HDLc level: <50 mg/dL for women <40 mg/dL for men
  4. High blood pressure ≥130/85 mmHg
  5. Fasting blood sugar ≥100 mg/dL - Pre-diabetes acceptable (glucose <125 mg/dL or HbA1c <6.5%)
• Subjects are also eligible if they are stably treated with statin drugs, anti-hypertensive medications, and anti-depressants. These are eligible as long as the drug category does not alter appetite, body weight, or the microbiome (if known).

Exclusion Criteria:

• Pregnant or lactating, or planning to become pregnant
• BMI of <20.0 or >40.0 kg/m2
• Use of tobacco products
• Uncontrolled hypertension and blood pressure ≥ 180/110
• Use of medications that affect the gut microbiome (e.g., antibiotics)
• Taking medications known to affect appetite (phentermine) or gastrointestinal function (e.g. metformin)
• On a special diet vegetarian, or other restricted dietary patterns
• Undergoing weight loss
• Ad libitum intake of fiber above 25 g/day (mean intake in the US population is 17 g/day) and also an intake of fiber <10 g/d
• Ad libitum alcohol intake of greater than 7 drinks/week for women and 14 drinks/week for men
• History of disease (example colon cancer, etc.)
• Live more than 45 miles away from the University because participants will need to come into the Lab every 3 days or so to pick up meals.

Control Arm Inclusion criteria

• Men and women
• Age 45-65y: the average age of people referred for a screening colonoscopy
• Scheduled for a health-screening colonoscopy
• Willing to provide fecal samples
• Subjects are also eligible if they are stably treated with statin drugs, anti-hypertensive medications, and anti-depressants. These are eligible as long as the drug category does not alter appetite, body weight, or the microbiome (if known).

Exclusion criteria

• Pregnant or lactating, or planning to become pregnant
• Use of medications that affect the gut microbiome (e.g., antibiotics within the past 30 days)
• History of disease (example colon cancer, active GI bleeding, inflammatory bowel disease, etc.)
• Live more than 45 miles away from the University because participants will need to come into the Lab every 3 days or so to deliver fecal samples.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Fiber; Subjects are provided a high-fiber diet for 2 weeks. Tests include: blood biochemistries, body composition measured via DEXA, fecal sample collection, and anthropometrics measured	Dietary supplement: High fiber; A pea fiber supplement is added to a diet of regular foods. Participants receive 25g fiber daily.
No Intervention: Control; Subjects are not provided any diet, instead they eat what they choose for two weeks while they participate in a series of tests including: fecal sampling, food records, questionnaires/surveys, and anthropometrics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in microbial composition as measured by 'alpha diversity'	Measured via fecal sample. Intervention group - measured once before scheduled health screening colonoscopy and 2 times over 2 weeks post-colonoscopy (day 1, 7, 14). Control group - measured once before scheduled health screening colonoscopy and 5 days over 2 weeks post-colonoscopy (day 3, 5, 8, 11, 14). Variability in microbial composition refers to how many different kinds of microbes are present in the fecal sample. We are testing the possibility that the more kinds of microbes, the healthier the person. The higher the measure the alpha diversity, the greater the number of different microbes.	2 weeks
Concentration of SCFA	Measured via fecal sample. Intervention group - measured once before scheduled health screening colonoscopy and 2 times over 2 weeks post-colonoscopy (day 1, 7, 14). Control group - measured once before scheduled health screening colonoscopy and 5 days over 2 weeks post-colonoscopy (day 3, 5, 8, 11, 14).	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose concentration (mg/dL)	Measure changes in fasting blood glucose concentration following the short-term, high-fiber feeding period. Blood taken at screening, baseline, and follow up.	2 weeks
Blood lipid concentation (total cholesterol, LDLc, HDLc) (mg/dL)	Measure changes in fasting blood lipid concentration (mg/dL) following the short-term, high-fiber feeding period. Blood taken at screening, baseline, and follow up.	2 weeks

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: Elizabeth Parks, University of Missouri-Columbia; Principal Investigator: Yezaz Ghouri, MD, University of Missouri-Columbia; Principal Investigator: Katherene Anguah, PhD, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: August 28, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: colonoscopy; fiber
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 2053546

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No