The Role of Dietary Titanium Dioxide on the Human Gut Microbiome and Health

NCT05864352 | Completed

• 1 other identifier: 21-122-MAN-XPD
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal will quantify dietary exposure of a nano- food additive in the U.S. food supply, and determine its impact on the human gut microbiome, gut inflammation, permeability and oxidative stress. Titanium dioxide (TiO2, or E171 food grade additive) is used in processed foods, with thousands of tons produced annually and an expected increase \>8.9% from 2016 to 2025. Preclinical models demonstrate \>99% of consumed TiO2 is retained within the intestinal lumen and excreted in the feces. In animal models, dietary TiO2 causes shifts in the gut microbiome, decreases acetate production, increases biofilm formation, and causes profound disruption of gut homeostasis and intestinal tight junctions, due to the production of reactive oxygen species and increased inflammation. However, the relation between chronic TiO2 intake and human gut homeostasis has yet to be elucidated. France issued an executive order to ban food grade TiO2 use after January 1st 2020, over serious safety concerns. Since then, multiple European civil societies have jointly called for an executive order to ban TiO2 across the EU. Typical TiO2 intake among U.S. adults remains to be documented, and there are no known studies that estimate dietary exposure of TiO2 using a whole foods approach. Therefore, the overarching goals of this project are to: 1) measure dietary TiO2 exposure in a sample of U.S. adults, using dietary recalls and fecal TiO2 content; 2) determine how fecal TiO2 content is related to gut dysbiosis, metatranscriptomics, intestinal inflammation, permeability and oxidative stress.

Conditions

Inflammation; Microbiota; Gastrointestinal Irritation

Outcome Measures

Primary Outcomes (1)

• Gut microbiota taxonomy and expressed pathways

  To evaluate the phylogeny and taxonomy of the gut microbiota in each of the three fecal samples per participant, fecal DNA and RNA will be isolated and purified and subject to Illumina-tag PCT to amplify 16S rRNA genes. Samples will be subject to metatranscriptomics sequencing to compare microbial community level expression signatures associated with fecal TiO2.

  During the study week, three consecutive day period.

Secondary Outcomes (3)

• Concentration of Intestinal Inflammation Biomarkers in Feces

  During the study week, three consecutive day period.

• Concentration of Intestinal Homeostasis and Permeability Biomarkers in Feces

  During the study week, three consecutive day period.

• Concentration of Intestinal Oxidative Stress Biomarkers in Feces

  During the study week, three consecutive day period.

Study Arms (2)

High TiO2 Consumer

Participants with an estimated TiO2 stool content greater than the cohort median content, μg/mg dry stool.

Low TiO2 Consumer

Participants with an estimated TiO2 stool content less than the cohort median content, μg/mg dry stool.

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from the greater Lowell area, Massachusetts.

You may qualify if:

• Healthy persons between the ages of 18 to 30 y.

You may not qualify if:

• \<18 years and \>30 years
• antibiotic use in the past 6 months
• laxative use in the past 30 days
• self-reported fever, cancer, or gastrointestinal disease (e.g., inflammatory bowel diseases, C. difficile infection
• use of selective serotonin reuptake inhibitors (SSRI's)
• use of non-steroidal anti-inflammatory drugs (NSAIDs) within 10 days
• daily use of proton pump inhibitors
• history of gastrointestinal alteration (e.g., appendectomy, gastric bypass surgery)
• pregnancy.

Sponsors & Collaborators

• University of Massachusetts, Lowell: lead
• United States Department of Agriculture (USDA): collaborator
• Wright Labs: collaborator

Study Sites (1)

University of Massachusetts

Lowell, Massachusetts, 01854, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Three consecutive fecal samples frozen at -80 degrees C

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kelsey M Mangano, PhD

  University of Massachusetts, Lowell

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: May 18, 2023
• Study Start: September 22, 2021
• Primary Completion: November 18, 2022
• Study Completion: November 28, 2022
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)