Healthy Adults
Conditions
Keywords
Intestine, Gut, Metabolites, Microbiota
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.
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.
Interventions
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Effect of BSS on the Human Gut Microbiome. | Through Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Effect of BSS on the Human Gut Metabolome. | Through Day 28 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSuchitra K Hourigan, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Participant flow
Recruitment details
Participants were recruited from June 2023 through October 2024. All recruitment took place at the National Institute of Allergy and Infectious Disease.
Pre-assignment details
Baseline visits were completed after confirmation of eligibility. The overlap between the screening and baseline windows accounted for the required 30-day interval between the optional colonoscopies at baseline and day 8. Participants who did not undergo colonoscopy may have a shorter interval between screening, baseline, and day 0 once eligibility is confirmed. Some participants did not meet criteria to continue based on medication use, scheduling issues, and enrollment in other trials.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Baseline Colonoscopy Baseline Colonoscopy Complete | 13 Participants |
| Baseline Colonoscopy Baseline Colonoscopy Incomplete | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 20 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
None listed