Analysis of MicroBial Metabolites After Eating Refined Food

NCT04308473 | Active Not Recruiting

• 1 other identifier: 19-1623
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn more about what happens in the human body after consuming a meal that contains ultra-processed foods like hamburgers, and if this is different to what happens after consuming a meal that contains lots of whole foods, like fresh vegetables, instead.

Conditions

Dietary Habits

Keywords

Gastrointestinal Microbiome; Ultra-processed Food

Outcome Measures

Primary Outcomes (2)

• Serial changes in plasma and urine metabolites and biomarkers

  Serial changes in plasma and urine metabolites and biomarkers

  Pre-meal (baseline) & post-meal at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours

• Serial changes in plasma and urine TMAO

  Serial changes in plasma and urine TMAO (trimethylamine N-oxide)

  Pre-meal (baseline) & post-meal at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours

Study Arms (4)

Arm 1: Ultra-processed Meal + Antibiotics to supress gut flora

EXPERIMENTAL

Subjects in Arm 1 will take antibiotics for 3 days before the meal challenge to suppress the gut flora. The antibiotics to be used are: vancomycin, 125 mg three times daily; metronidazole, 500 mg twice daily; ciprofloxacin, 500 mg twice daily; and neomycin, 1 gram three times daily. These subjects will then consume a challenge meal of ultra-processed foods.

Other: Ultra-processed Food Meal

Arm 2: Ultra-processed Meal + No Antibiotics

EXPERIMENTAL

Subjects in Arm 2 will not take any antibiotics prior to the meal challenge. They will consume a challenge meal of ultra-processed foods.

Other: Ultra-processed Food Meal

Arm 3: Whole Food Meal + Antibiotics to supress gut flora

EXPERIMENTAL

Subjects in Arm 3 will take antibiotics for 3 days before the meal challenge to suppress the gut flora. The antibiotics to be used are: vancomycin, 125 mg three times daily; metronidazole, 500 mg twice daily; ciprofloxacin, 500 mg twice daily; and neomycin, 1 gram three times daily. These subjects will then consume a challenge meal of whole, unprocessed foods.

Other: Whole Food Meal

Arm 4: Whole Food Meal + No Antibiotics

EXPERIMENTAL

Subjects in Arm 4 will not take any antibiotics prior to the meal challenge. They will consume a challenge meal of whole, unprocessed foods.

Other: Whole Food Meal

Interventions

Ultra-processed Food Meal OTHER

An ultra-processed diet challenge test utilizing 1) potatoes fried in highly refined and processed vegetable oil, including corn, soybean, or canola oil, with wheat and milk derivatives; 2) a beef patty sandwich containing processed American cheese, enriched refined flour, mold inhibitor, preservatives and oxidation/reduction additives such as ascorbic acid, potassium/calcium iodate, alpha-amylase, and azodicarbonamide; and 3) a beverage composed of carbonated water, high fructose corn syrup and caramel coloring. The ultra-processed challenge meal will be obtained from a local restaurant on the day of the challenge test.

Arm 1: Ultra-processed Meal + Antibiotics to supress gut flora; Arm 2: Ultra-processed Meal + No Antibiotics

Whole Food Meal OTHER

A whole food diet challenge test utilizing 1) a side salad comprised of fresh leafy vegetables, and typical whole food toppings including fresh onion, fresh tomato, fresh carrots, and raw walnuts with a pure unrefined olive oil salad dressing; 2) a legume-based main dish including chickpeas, lentils and whole grain quinoa; 3) a fresh berry-rich smoothie beverage consisting of organic blueberries, raspberries, strawberries, bananas, and fresh orange juice. The whole food challenge meal will be made by the study team from readily available commercial foods bought from local grocery stores.

Arm 3: Whole Food Meal + Antibiotics to supress gut flora; Arm 4: Whole Food Meal + No Antibiotics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women age 18 years or above.
• Able to provide informed consent and comply with study protocol
• Able to remain on a stable aspirin regimen (either on or off aspirin or aspirin products) for 1 week prior to starting study until the end of the study period.

You may not qualify if:

• Significant chronic illness or end-organ dysfunction, including known history of uncompensated heart failure, renal failure, pulmonary disease, hematologic diseases.
• Active infection or received antibiotics within 6 months of study enrollment.
• Use of over-the-counter probiotic within past month.
• Chronic gastrointestinal disorders.
• Intolerance to probiotic therapy.
• Allergy to vancomycin, ciprofloxacin, neomycin, metronidazole, or lactose.
• Allergy to any of the food components of the challenge meals.
• Having undergone bariatric procedures or surgeries such as gastric banding or bypass.
• Pregnancy.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

Related Publications (7)

• Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.

  PMID: 23614584 BACKGROUND

• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

  PMID: 21475195 BACKGROUND

• Schugar RC, Shih DM, Warrier M, Helsley RN, Burrows A, Ferguson D, Brown AL, Gromovsky AD, Heine M, Chatterjee A, Li L, Li XS, Wang Z, Willard B, Meng Y, Kim H, Che N, Pan C, Lee RG, Crooke RM, Graham MJ, Morton RE, Langefeld CD, Das SK, Rudel LL, Zein N, McCullough AJ, Dasarathy S, Tang WHW, Erokwu BO, Flask CA, Laakso M, Civelek M, Naga Prasad SV, Heeren J, Lusis AJ, Hazen SL, Brown JM. The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue. Cell Rep. 2017 Jun 20;19(12):2451-2461. doi: 10.1016/j.celrep.2017.05.077.

  PMID: 28636934 BACKGROUND

• Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016 Jun 2;165(6):1332-1345. doi: 10.1016/j.cell.2016.05.041.

  PMID: 27259147 BACKGROUND

• Srour B, Fezeu LK, Kesse-Guyot E, Alles B, Mejean C, Andrianasolo RM, Chazelas E, Deschasaux M, Hercberg S, Galan P, Monteiro CA, Julia C, Touvier M. Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Sante). BMJ. 2019 May 29;365:l1451. doi: 10.1136/bmj.l1451.

  PMID: 31142457 BACKGROUND

• Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, Chung ST, Costa E, Courville A, Darcey V, Fletcher LA, Forde CG, Gharib AM, Guo J, Howard R, Joseph PV, McGehee S, Ouwerkerk R, Raisinger K, Rozga I, Stagliano M, Walter M, Walter PJ, Yang S, Zhou M. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019 Jul 2;30(1):67-77.e3. doi: 10.1016/j.cmet.2019.05.008. Epub 2019 May 16.

  PMID: 31105044 BACKGROUND

• Tang ZZ, Chen G, Hong Q, Huang S, Smith HM, Shah RD, Scholz M, Ferguson JF. Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites. Front Genet. 2019 May 17;10:454. doi: 10.3389/fgene.2019.00454. eCollection 2019.

  PMID: 31164901 BACKGROUND

MeSH Terms

Conditions

Feeding Behavior

Condition Hierarchy (Ancestors)

Behavior, Animal; Behavior

Study Officials

• W. H. Wilson Tang, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Model Details: Group 1 = Ultra-Processed Food Meal + Antibiotics to suppress gut flora; Group 2 = Ultra-Processed Food Meal with No Antibiotics; Group 3 = Whole Food Meal + Antibiotics to suppress gut flora; Group 4 = Whole Food Meal with No Antibiotics

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 16, 2020
• Study Start: September 1, 2020
• Primary Completion: February 28, 2023
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)