Dietary Fiber Effects on the Microbiome and Satiety

  • STATUS
    Recruiting
  • End date
    Aug 1, 2025
  • participants needed
    88
  • sponsor
    University of Missouri-Columbia
Updated on 24 October 2021

Summary

Strong evidence supports the association between high fiber (HiFi) diets (e.g. legumes, nuts, vegetables) and a reduced risk for chronic conditions such as cardiovascular disease (CVD), type 2 diabetes and some forms of cancer. However, the current U.S. average consumption of dietary fiber of 17g/day is significantly below the recommendation level of 25g/d for women and 38g/d for men. Furthermore, fiber fermentation to produce short chain fatty acid (SCFA) products and alterations in microbial composition and activity may be mechanisms linking a HiFi diet to improved health. Importantly, much of the data, including findings supporting a beneficial role of SCFA have been derived from animal studies. Human studies are now needed to advance the understanding of the translational significance of rodent studies and the potential benefit of fiber on microbial metabolites and cardiometabolic health, glucose regulation, appetite and satiety. The central hypothesis is that that the mechanisms by which dietary fiber provides metabolic benefit include direct physical effects in the upper gastrointestinal tract to slow nutrient absorption, and indirect effects to reduce food intake mediated by SCFA-induced secretion of intestinal hormones resulting in increased satiety. Design: Using fiber derived from peas, Aim 1 will test the effect of a HiFi diet on appetite, satiety, and cardiometabolic health and whether elevated SCFA concentration mediates improved satiety in 44 overweight/obese subjects randomly assigned to receive either a high fiber or a low fiber dietary intervention for four weeks in a parallel arm-repeated measures design. Aim 2 will quantitate the changes in microbial composition and colonic SCFA production rate during HiFi feeding and whether any changes are potential mediators of observed benefits on satiety and cardiometabolic risk factors in 26 subjects assigned to receive a high fiber intervention for 3 weeks in a repeated measures design. Relevance: These studies will significantly expand the understanding of mechanisms by which dietary fiber improves satiety and cardiometabolic health in humans.

Description

Dietary patterns with high fiber content are linked to a lower risk for the development of cardiovascular disease [1-3], hypertension [4], type 2 diabetes [5] and increased body weight [4]. Potential biological mechanisms that may mediate these beneficial health effects include a slowing of the absorption of meal carbohydrate (CHO) [6-11], reduction in blood lipids [8,12] and an increase in the release of satiety hormones [10,13]. The PI has previously shown that compared to low-fiber (LowFi) meals, high-fiber (HiFi) meals reduced blood glucose concentrations postprandially by 11% [14]. Another potential mechanism is a postulated role for microbial fiber fermentation to improve health through production of the short chain fatty acids (SCFA) acetate, propionate, and butyrate [15-17]. In addition to promoting colon health, butyrate production may stimulate release of the gut hormones, glucagon-like peptide-1 GLP-1 and peptide YY (PYY) [18] resulting in improved appetite regulation [19]. Since the seminal paper of Gordon in 2004 [20], a large body of research has uncovered the critical role that gut microbes play in health. Importantly, much of these data, including findings supporting a beneficial role of SCFA [21-23] have been derived from animal studies. Human studies are now needed to advance the translational significance of rodent studies and the potential benefit of fiber on microbial metabolites and cardiometabolic health, glucose regulation, appetite and satiety. The current study will determine the effects of dietary fiber intake on appetite, intestinal metabolism, and the microbiome. We hypothesize that the mechanisms by which dietary fiber provides metabolic benefit include direct physical effects in the upper gastrointestinal (GI) tract to slow nutrient absorption and indirect effects to reduce food intake mediated by SCFA-induced secretion of GI hormones resulting in increased satiety. To test this hypothesis, we will conduct a randomized controlled trial of 4 weeks of HiFi or LowFi diets in 44 subjects (specific aim 1, SA1) and also leverage a screening colonoscopy to standardize baseline microbial populations for a 3-week, pre- and post HiFi intervention study in 26 subjects (SA2) with metabolic syndrome. We will assess the effects of the diets on appetite and satiety, cardiometabolic risk and intestinal metabolism at the beginning and at the end of the feeding interventions. The fiber chosen is derived from peas, as recent data suggest that legumes significantly improve glycemia [6,24-27], diabetes [28,29], heart disease risk [30], and risk for obesity [31]. These methods will be employed to accomplish two specific aims.

SA1a: Test the effect of a HiFi diet on appetite and satiety and whether SCFA production mediates improved satiety in HiFi feeding. Hypothesis (H) 1a: In adult men and women, the HiFi (n=22) compared to the LowFi (n=22) diet will significantly improve markers of satiety (GLP-1, PYY, subjective appetite ratings) and lower activation in brain regions that control food intake/reward/appetite while increasing activation in executive control regions during functional magnetic resonance imaging (fMRI) visual food cues. These changes will be related to higher postprandial SCFA concentrations and altered microbial populations as evidenced by greater bifidobacteria levels and low Firmicutes to Bacteroidetes ratio.

SA1b: Determine whether a HiFi diet improves cardiometabolic health. H1b: A HiFi diet will result in lower glycemia, blood lipids, blood pressure, and waist circumference compared to a LowFi diet.

SA2: Quantitate the changes in microbial composition and colonic SCFA production rate (using stable isotopic infusion techniques) on HiFi diet feeding (n=26) and whether any changes are potential mediators of observed benefits on satiety and cardiometabolic risk factors. H2: A significant microbial species reduction will follow colonoscopy bowel prep, and repopulation after HiFi will be characterized by greater bifidobacterial and low Firmicutes/Bacteroidetes ratio. An increase in SCFA flux following HiFi will be associated with improvements in microbial composition and postprandial markers of satiety and blood triglycerides and glucose excursions.

Sample size Based on our own published [14] and unpublished data, and that from others [32-35], a power analysis revealed that a sample size of between 10 to 20 subjects/group is needed to detect significant differences in key variables (alpha 0.05) and a power of 90% (15 to 18 subjects/group with 80% power). For specific aim 1, we will add 2 subjects/group to account for a 10% subject dropout and for specific aim 2, we will add an additional 6 subjects to account for 30% dropout. Thus, for specific aim 1 44 subjects (22/group) and for specific aim 2, 26 subjects are analyzed in a repeated-measures design. We believe any dietary fiber effect smaller than past, published treatments will be balanced by the relative 'clean' starting point of the colon after colonoscopy (specific aim 2) and also by the fact that we are providing all study meals and hence fully controlling the subject's intake

Data analysis:

Statistical analysis will be performed with SPSS software (version 25). Graphical methods are used to assess the appropriateness of assuming linear relationships and histograms and probability plots used to assess the normality of residuals. Transformation or non-parametric methods will be, employed as needed. Fasting glucose and hormones concentrations will be, obtained serially - both acutely after meals and in the fasting state before and after the diets. Changes over time (treated as a nominal factor so as not to assume a linear trend) and by diet in the composition of the microbiome will be assessed by grouping into the dominant bacterial phyla (i.e. Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes) and genus. For SA1, a two-factor ANOVA will be used for each outcome, with the factors being Group, Time and the Group by Time interaction. The groups are constructed via matched-sample randomization, so we expect comparability at baseline. For SA2, a paired sample t-test will be used to compare outcomes of interest. Results will be reported as group means or medians, as most appropriate for the data along with 95% confidence intervals for the summary statistics. Analyses of the fMRI data during visual stimulation are performed using Statistical Parametric Mapping 12 software (www.fil.ion.ucl.ac.uk/spm). Data are preprocessed, beginning with slice timing and realignment of the images to the mean image. The anatomical T1-weighted image is co-registered to the mean functional image. Normalization into Montreal Neurological Institute (MNI) space and Gaussian spatial smoothing is then performed. For each participant (first-level analyses), a general linear model is applied for the high- and low-caloric food and non-food image conditions. For each condition, a separate regressor is modeled by using a canonical hemodynamic response function that includes time derivatives. Movement parameters are, modeled as confounders. For second level analysis, a mixed model ANOVA is used, with the within-factor, image condition (high calorie food, low calorie food, non-food|) and the between-factor group (HiFi vs LowFi). A priori regions-of-interest (ROIs) such as, insula, orbitofrontal cortex, amygdala, and prefrontal cortex are examined for potential group-by-food image interactions (the effect of most interest). Whole-brain analyses are also conducted (corrected for multiple comparisons) to identify other potential ROIs.

Details
Condition Dietary Fiber
Treatment Dietary fiber: 10-25g, Dietary fiber: 5g
Clinical Study IdentifierNCT04611217
SponsorUniversity of Missouri-Columbia
Last Modified on24 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Men and women (premenopausal only)
Age 20-55y (Aim 1); 45-55y (Aim 2)
BMI 25 or 35 kg/m2 (Aim 1); 25 or 40 (Aim 2)
Weight stable (no fluctuations in body weight of greater than 4 kg in the last 3 months)
Willing to consume a research diet
Willing to provide blood and fecal samples
At least one characteristic of the metabolic syndrome (but not diabetic)
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%)
Stably treated with statin drugs, anti-hypertensives, and anti-depressants. These are acceptable as long as the drug category does not alter appetite, body weight, or the microbiome (if known)

Exclusion Criteria

Pregnant or lactating
Postmenopausal (evidence suggests an interplay between the gut microbiome)
BMI of <25 or >35 kg/m2 (Aim 1); <25 or >40 kg/m2 (Aim 2)
Use of medications that affect the gut microbiome (e.g. antibiotics)
Taking medications known to affect appetite (e.g., phentermine) or gastrointestinal function (e.g., metformin)
On a special diet or undergoing weight loss, vegetarian, or other restricted dietary patterns
Ad libitum intake of fiber above 25g/day (mean intake in the US population is 17g/day) and < 10g/d
Ad libitum alcohol intake of greater than 1 drink/d for women and 2 drinks/d for men
History of disease (example colon cancer, HIV, cardiovascular disease, psychiatric disorders, etc.)
Use of tobacco products
Having metal or implants in the body that are not MRI compatible (Aim 1 only)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note