Fermented and Fiber-rich Food (FeFiFo) Study

Microbiota-targeted Dietary Strategies to Reduce Inflammatory Markers of Americans: High Fiber vs Fermented Food

The primary objective is to contrast the degree to which increased consumption of dietary fiber vs. fermented food can decrease inflammation, increase microbiota diversity and can impact microbiota production of short-chain fatty acids (SCFA), potential normalizers of metabolic and immune dysfunction, in obese and non-obese adults.

Study Overview

• Status: Completed
• Conditions: Inflammation; Metabolic Syndrome; Microbiome; Immune Function
• Intervention / Treatment: Behavioral: Dietary Fiber; Behavioral: Fermented Foods

Detailed Description

The gut microbiota is central to human health, and the modern, industrialized gut microbiota has been linked to numerous chronic diseases that are driven by inflammation. It is likely dietary changes in the last half-century consistent with adoption of the Western diet have had an adverse impact on the gut microbiota. A critically important next step in this field of research is to identify how different dietary interventions can potentially restore healthy features of the gut microbiota in alignment with the optimization of human health. Dietary interventions that target the microbiota and reduce inflammation may reverse or prevent chronic diseases including obesity, metabolic syndrome, and inflammatory bowel disease. This study is designed to elicit and contrast inflammatory markers in blood with the amount of increase in microbiota diversity and related metabolic output achievable by two dietary approaches commonly available to the general population. The results could contribute to dietary recommendations for reversing the chronic disease epidemics of Westernization.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 and older, both genders, all ethnic backgrounds
• Healthy subjects willing and able to provide blood, as well as stool specimens
• Able to provide signed and dated informed consent.

Exclusion Criteria:

• Body Mass Index higher than 40.
• Vital signs outside of acceptable range at Screening Visit, i.e., blood pressure greater than 160/100, oral temperature greater than 100 degrees F, pulse greater than 100.

• Use of any of the following drugs within the last 6 months:

  1. systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral);
  2. oral, intravenous, intramuscular, nasal or inhaled corticosteroids;
  3. cytokines;
  4. methotrexate or immunosuppressive cytotoxic agents;
  5. large doses of commercial probiotics consumed (greater than or equal to 10e8 cfu or organisms per day) - includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component.
  6. consumption of > 20 g fiber/day and > 7 servings of fermented foods per week.
• Acute disease at the time of enrollment (defer sampling until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.
• Chronic, clinically significant (unresolved, requiring on-going medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality, as determined by medical history or physical examination.
• History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
• Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
• Recent history of chronic alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day.
• Positive test for HIV, HBV or HCV.
• Any confirmed or suspected condition/state of immunosuppression or immunodeficiency ( primary or acquired) including HIV infection.
• Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.

• History of active uncontrolled gastrointestinal disorders or diseases including:

  1. inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis;
  2. irritable bowel syndrome (IBS) (moderate-severe);
  3. persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated);
  4. chronic constipation.

Female who is pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fiber Group; Participants are asked to increase their usual dietary fiber intake by 20 grams/day.	Behavioral: Dietary Fiber
Experimental: Fermented Foods Group; Participants are asked to consume 6 servings of fermented foods per day.	Behavioral: Fermented Foods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune profile: Cytokine Response Score (CRS)	Change from baseline in CRS at 10 weeks	Baseline and 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota metabolites: short-chain fatty acids (SCFA)	Change from baseline in short-chain fatty acids (SCFA) at 10 weeks.	Baseline and 10 weeks
Microbiota composition	Change from baseline in 16S rRNA enumeration at 10 weeks, determined using Illumina-based sequencing.	Baseline and 10 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Christopher D Gardner, PhD, Stanford University; Principal Investigator: Justin L Sonnenburg, PhD, Stanford University

Publications and helpful links

General Publications

• Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 Aug 5;184(16):4137-4153.e14. doi: 10.1016/j.cell.2021.06.019. Epub 2021 Jul 12.

Helpful Links

• Study description and results summary

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2016
• Primary Completion (Actual): June 2, 2017
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: September 6, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Inflammation; Metabolic Syndrome
• Other Study ID Numbers: 36643

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