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

An Exploratory Study of The Effect of Bismuth Subsalicylate on The Gut Microbiome and Host Response in Healthy Adults

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: Bismuth subsalicylate

Detailed Description

Study Description:

This is a single-site, single-arm, open-label study to evaluate the effect of bismuth subsalicylate (BSS) on the human gut microbiome and host immune response. Upon confirmation of eligibility, healthy adult volunteers will provide stool and optional blood, saliva, urine, and intestinal biopsy samples for a baseline assessment of gut microbiome and host immune response. Up to 18 weeks later, participants will undergo a 2-day/8-dose regimen of oral BSS. Stool will be collected at baseline, days 2 (+3), 8 (+/-3), 14 (-3/+7) and 28 (+/-7). Blood, saliva, and urine are also optional at these time points. Participants may also undergo a second optional colonoscopy at day 8 (+/-3) to provide colon biopsies for research analysis.

Primary Objective:

To evaluate the effect of BSS on the human gut microbiome.

Secondary Objective:

To evaluate the effect of BSS on the human gut metabolome.

Tertiary/Exploratory Objective:

To evaluate the effect of BSS on the systemic and intestinal host response (immune and inflammatory responses).

Primary Endpoint:

Differences in the relative abundance of taxa in stool samples pre-BSS and approximately 1 month post-BSS. Differences in microbiome metrics of alpha diversity and beta diversity will also be assessed.

Secondary Endpoint:

Differences in the stool metabolome (including short chain fatty acids, bile acids, and untargeted metabolomics) pre-BSS and approximately 1 month post-BSS.

Tertiary/Exploratory Endpoint:

Differences in systemic host immune and inflammatory responses, such as cytokines and immune cells, and host intestinal immune responses, such as specific T-cell populations in intestinal biopsies pre-BSS and approximately 1 month post-BSS.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.
• Any condition that, in the opinion of the study team, contraindicates participation in this study.

Co-enrollment in other studies is restricted. Consideration for co-enrollment in clinical trials evaluating the use of a licensed medication will require the approval of the principal investigator. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate the Effect of BSS on the Human Gut Metabolome.	In the context of stool metabolome analysis, the number of differentially abundant metabolites refers to the count of metabolites whose levels significantly differ between baseline and 28 days post-BSS. To determine this, we performed broad targeted metabolomic profiling of stool samples collected at both timepoints. Metabolites were identified and quantified, and significant changes in abundance were calculated. The total number of differentially abundant metabolites provides a measure of the metabolic shifts in the gut environment following BSS administration.	Through Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 2 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 2
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 2 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 2 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 2
To Evaluate the Effect of BSS on the Human Gut Microbiome.	Beta diversity refers to the variation in bacterial composition among samples, which we measured utilizing the Bray-Curtis dissimilarity Index. Bray-Curtis is used 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. Bray-Curtis was then calculated using read counts per species per sample to quantify the differences in community composition between samples at baseline and 2 days post-BSS administration. Bray-Curtis dissimilarities were calculated between samples and visualized using principal coordinates analysis (PCoA); values along the second ordination axis (PCoA2) used for downstream analysis.	Through Day 2.
To Evaluate the Effect of BSS on the Human Gut Metabolome.	In the context of stool metabolome analysis, the number of differentially abundant metabolites refers to the count of metabolites whose levels significantly differ between baseline and 2 days post-BSS. To determine this, we performed broad targeted metabolomic profiling of stool samples collected at both timepoints. Metabolites were identified and quantified, and significant changes in abundance were calculated. The total number of differentially abundant metabolites provides a measure of the metabolic shifts in the gut environment following BSS administration.	Through Day 2

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Suchitra K Hourigan, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2023
• Primary Completion (Actual): December 15, 2024
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: July 1, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Microbiota; Metabolites; Intestine; Gut
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Antidiarrheals; bismuth subsalicylate
• Other Study ID Numbers: 10001631; 001631-I

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