Effect of Bismuth Subsalicylate on the Gut Microbiome and Host Response in Healthy Adults

NCT05930197 | Completed Phase 1 Results

• 2 other identifiers: 10001631001631-I
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Many kinds of good or normal bacteria live on your skin and inside your stomach and intestines (gut). These bacteria are important to your health. What you eat, where you live, and what medicines you take can affect the bacteria in your gut. Bismuth subsalicylate (BSS) is an ingredient in common medicines for mild diarrhea and stomach pain. Products that contain BSS include Pepto-Bismol, Kao-Tin, and Pink Bismuth. But how BSS affects the bacteria in a person s gut is not fully understood. Objective: To see how BSS affects gut bacteria in healthy people. Eligibility: Healthy people aged 18 to 50 years. Design: Participants will have 6 clinic visits in up to 18 weeks. Only 1 visit must be at the NIH clinic; others may be either in-person or remote. BSS is a liquid taken by mouth. Participants will take a dose of BSS 4 times a day for 2 days. They will take the same amount of BSS as a person would take to treat diarrhea or related problems. Stool samples will be collected at each study visit. For remote visits, participants will be given a collection kit; they will collect the sample at home and send it in. Participants will take surveys at each visit. They will answer questions about their diet and health. Participants may also provide optional samples of blood, saliva, and urine. Participants may have up to 2 optional colonoscopies. A long tube will be inserted via the rectum to collect tissue samples from the intestine. Participants will be sedated or placed under anesthesia for the procedure.

Conditions

Healthy Adults

Keywords

Intestine; Gut; Metabolites; Microbiota

Outcome Measures

Primary Outcomes (3)

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  In the context of gut microbiome analysis, this measure represents the number of bacterial taxa that are significantly different between the two timepoints (baseline and 28 days post BSS) based on the read counts which represent abundance of taxa. We used shotgun metagenomic sequencing to analyze the gut microbiome. Sequenced reads were mapped to a reference database, and the read count abundance of each taxon was calculated. Statistical analysis was performed to identify the number of taxa that are significantly different between timepoints.

  Through Day 28

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  Difference of alpha diversity stool samples by Shannon index at baseline (before study drug administration) and 28 days after BSS. In the context of gut microbiome analysis, the Shannon Index represents a measure of alpha diversity (measure of diversity of a microbial community). The Shannon Index is a value greater than 0 with lower values indicating lower diversity and higher values indicating higher diversity, generally between 1.5 and 3.5, and usually \< 4.5. To evaluate changes in the gut microbiome, we compared the mean change in the Shannon Index at baseline and 28 days post-BSS. Shotgun metagenomic sequencing was performed, and sequenced reads were mapped to a reference database to identify and enumerate based on read count unique taxa present in each sample. Statistical analysis was then used to determine whether there were significant differences in the Shannon Index between the two timepoints, providing insight into shifts in microbial diversity following BSS administration.

  Through Day 28.

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  Difference of beta diversity stool samples at baseline (before study drug administration) and 28 days after BSS. Beta diversity refers to the variation in bacterial composition among samples, which we measured utilizing the Bray-Curtis dissimilarity Index. The Bray-Curtis is a widely used metric to quantify beta diversity, reflecting the degree of dissimilarity between samples, and its range is from 0 to 1, with 0 meaning no differences and 1 meaning completely dissimilar. This measure is essential for understanding changes in the bacterial composition over time. We used shotgun metagenomic sequencing to analyze the gut microbiome. Sequenced reads were mapped to a reference database, and the abundance of each taxon was calculated. The Bray-Curtis dissimilarity index was then calculated using read counts per species per sample to quantify the differences in community composition between samples at baseline and 28 days post-BSS administration.

  Through Day 28.

Secondary Outcomes (1)

• To Evaluate the Effect of BSS on the Human Gut Metabolome.

  Through Day 28

Other Outcomes (4)

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  Through Day 2

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  Through Day 2

• To Evaluate the Effect of BSS on the Human Gut Microbiome.

  Through Day 2.

Study Arms (1)

Interventional

EXPERIMENTAL

The oral suspension formulation of BSS will be used in this study. It is self administered at 1050mg 4 times per day (1 to 6 hours apart) for 2 days.

Drug: Bismuth subsalicylate

Interventions

Bismuth subsalicylate DRUG

BSS is a commonly used, widely available, OTC medication for a variety of gastrointestinal GI symptoms. It is available in the generic form, but also under the more commonly known brands: Bismatrol; Diotame; Geri-Pectate; Kao-Tin; Peptic Relief; Pepto-Bismol; Pink Bismuth and Stomach Relief. It received approval by the US Food and Drug Administration (FDA) in 1939.

Interventional

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• An individual must meet all the following criteria to be eligible for this study:
• Aged 18 to 50 years.
• In generally good health.
• Able to provide informed consent.
• Willing to allow samples and data to be stored and shared for future research.
• Participants who can become pregnant must agree to use one effective method of contraception when engaging in sexual activities that can result in pregnancy, beginning at the signing of the informed consent form (as early as week -18) until the final study visit. Acceptable methods of contraception include the following:
• External or internal condom with spermicide.
• Diaphragm or cervical cap with a spermicide.
• Hormonal contraception.
• Intrauterine device.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Use of systemic antibiotics in the last 3 months.
• BSS use in the last 3 months.
• Pregnant or breastfeeding.
• Allergy to BSS.
• Allergy to other salicylates (including aspirin).
• Current use of other salicylates (including aspirin).
• Current use of anticoagulant medications.
• History of or active GI ulcers.
• History of or active bleeding disorder.
• Bloody stool within the last 3 months.
• Diarrhea within the last 2 weeks (defined as three or more loose or liquid stools per day).
• Current use of medications that may have a drug interaction with BSS.
• Not proficient in written English.
• Currently participating in another clinical trial that may affect current study procedures, per investigator s discretion.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

bismuth subsalicylate

Limitations and Caveats

The study had several limitations. Only Fecal samples were analyzed, which cannot characterize specific parts of the gut. Fecal sulfides couldn't be measured due to preservation issues. Dietary variations could not be controlled for, and the BSS formulation included food dyes and flavorings, as well as salicylate, which may have influenced results. The study only included healthy adults aged 18-50, and as with all read-based microbiome studies, taxonomic classification may have been suboptimal.

Results Point of Contact

• Title: Suchitra Hourigan
• Organization: National Institute of Allergy and Infectious Disease

suchitra.hourigan@nih.gov

(240) 292-4552

Study Officials

• Suchitra K Hourigan, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2023
• First Posted: July 5, 2023
• Study Start: August 31, 2023
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: March 24, 2026
• Results First Posted: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)