Bismuth Subsalicylate for Gut Health in Healthy Adults

Overseen By Suchitra K Hourigan, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Antibiotics, Salicylates, Anticoagulants, others

Disqualifiers: Pregnancy, GI ulcers, Bleeding disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how bismuth subsalicylate, an ingredient in products like Pepto-Bismol, affects the beneficial bacteria in the gut. The aim is to understand its impact on gut health in healthy individuals. Participants will take bismuth subsalicylate orally for two days and provide stool samples to monitor changes in gut bacteria. Individuals in generally good health who haven't recently used antibiotics or bismuth subsalicylate may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to foundational scientific knowledge.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as antibiotics, BSS, salicylates (like aspirin), and anticoagulants, before participating. If you are on any of these, you may need to stop them to join the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that bismuth subsalicylate (BSS), found in products like Pepto-Bismol, is generally safe for short-term use. It commonly treats mild issues like diarrhea and stomach pain. Studies indicate that BSS can be safely used for a few days to a few weeks for these problems. However, in rare cases, it may cause serious issues like nerve damage. Most people tolerate it well, but following the dosage instructions is important. Using BSS for more than a couple of days without medical advice is not recommended. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bismuth Subsalicylate is unique because it uses bismuth to target gut health in a way that current options don't. Most treatments for gut issues focus on altering gut flora or easing symptoms like diarrhea, but bismuth works by forming a protective layer on the stomach lining and has antimicrobial properties. Researchers are excited because it could offer fast relief and protection without the need for antibiotics, potentially reducing the risk of antibiotic resistance.

What evidence suggests that Bismuth Subsalicylate might be an effective treatment for gut health?

Research has shown that bismuth subsalicylate (BSS) often helps with stomach issues like mild diarrhea and stomach pain. Studies have found that BSS effectively manages traveler's diarrhea and reduces the need for antibiotics in sudden diarrhea cases. It also helps prevent traveler's diarrhea, with users being 3.5 times more likely to avoid it. Although BSS is widely used for these conditions, its exact effects on gut bacteria remain unclear. Therefore, more research, including this trial, aims to explore its impact on gut health in healthy adults. ^{1 6 7 8 9}

Who Is on the Research Team?

Suchitra K Hourigan, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Healthy adults aged 18 to 50 who can consent and agree to use contraception if applicable. Excluded are those pregnant, breastfeeding, with recent diarrhea or bloody stools, poor English skills, on certain medications like antibiotics or anticoagulants within the last three months, using BSS recently, allergic to salicylates including aspirin, with bleeding disorders or GI ulcers.

Inclusion Criteria

Able to provide informed consent

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 baseline (as early as week -6) until the final study visit. Acceptable methods of contraception include external or internal condom with spermicide, diaphragm or cervical cap with a spermicide, hormonal contraception, intrauterine device.

In generally good health

Exclusion Criteria

I am currently taking aspirin or similar medications.

Not proficient in written English

Currently participating in another clinical trial that may affect current study procedures, per investigator's discretion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants provide baseline stool and optional blood, saliva, urine, and intestinal biopsy samples

1 week

1 visit (in-person or remote)

Treatment

Participants take BSS 4 times a day for 2 days

2 days

No additional visits required

Follow-up

Participants are monitored for changes in gut microbiome and host response with stool and optional blood, saliva, urine, and intestinal biopsy samples collected at specified intervals

4 weeks

5 visits (in-person or remote)

What Are the Treatments Tested in This Trial?

Interventions

• Bismuth Subsalicylate

Trial Overview The trial tests how Bismuth subsalicylate (BSS), found in over-the-counter treatments for stomach issues like Pepto-Bismol affects gut bacteria. Participants take BSS four times daily for two days and provide stool samples at each visit over up to 16 weeks. Optional blood, saliva, urine samples and colonoscopies may be involved.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a 21-day double-blind, randomized, placebo-controlled trial involving 128 young healthy adults, subsalicylate bismuth significantly reduced the incidence of diarrhea, with only 23% of participants experiencing diarrhea compared to 61% in the placebo group.

Participants taking subsalicylate bismuth not only had fewer cases of diarrhea but also experienced fewer intestinal complaints and a lower rate of enteropathogens in their stools, indicating its efficacy in preventing gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of traveler's diarrhea (emporiatric enteritis). Prophylactic administration of subsalicylate bismuth). DuPont, HL., Sullivan, P., Evans, DG., et al.[2022]

Pepto-Bismol, containing bismuth subsalicylate (BSS), is safe for use in treating gastrointestinal issues, with studies showing that even extended use for up to 6 weeks results in bismuth levels in the blood that are far below those associated with neurotoxicity.

The active ingredient, salicylic acid, is absorbed effectively, but the risk of toxicity remains low, as the peak plasma concentrations from the maximum daily dose are well below toxic levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bismuth subsalicylate: history, chemistry, and safety. Bierer, DW.[2019]

Bismuth subsalicylate (BSS), found in Pepto-Bismol, can interact with dietary components to form water-soluble products that are effective against Clostridium difficile, a harmful bacteria that can cause severe gastrointestinal issues.

This study utilized mass spectrometry and the agar dilution method to demonstrate the potential of BSS in treating infections, highlighting its mechanism of action through the transformation of insoluble compounds into soluble, active forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction of bismuth subsalicylate with fruit juices, ascorbic acid, and thiol-containing substrates to produce soluble bismuth products active against Clostridium difficile. Mahony, DE., Woods, A., Eelman, MD., et al.[2022]

All three bismuth compounds (De-Noltabs, Pepto-Bismol, and Roter) significantly reduced intragastric urease activity in Helicobacter pylori-positive patients after just one day of dosing, indicating their efficacy in suppressing H. pylori.

The study found no significant difference in effectiveness among the three compounds, suggesting that their action occurs locally in the stomach rather than requiring systemic absorption of bismuth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of one-day oral dosing with three bismuth compounds for the suppression of Helicobacter pylori assessed by the 13C-urea breath test. Prewett, EJ., Luk, YW., Fraser, AG., et al.[2019]

The NSAID BFMeT induced ileal ulcers in rats, but this effect was completely prevented in rats treated with antibiotics or those that were germ-free, indicating that intestinal bacteria play a crucial role in ulcer formation.

Specific beneficial bacteria, such as Bifidobacterium and Lactobacillus, were found to inhibit ulcer formation by suppressing the growth of harmful Gram-negative bacteria associated with ulcers, suggesting a protective mechanism against NSAID-induced damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug. Uejima, M., Kinouchi, T., Kataoka, K., et al.[2019]

In a study evaluating treatments for Helicobacter pylori infection, both clindamycin combined with bismuth subsalicylate and bismuth alone improved clinical symptoms like abdominal pain and heartburn, but microbiological cure rates were very low, with only 1 out of 11 patients achieving success with bismuth alone.

The results suggest that treating H. pylori may require a combination of multiple antibiotics or additional medications to enhance effectiveness, as neither treatment group achieved significant eradication of the bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind randomized trial of bismuth subsalicylate and clindamycin for treatment of Helicobacter pylori infection. Westblom, TU., Madan, E., Subik, MA., et al.[2019]

Bifidobacterium animalis ssp. lactis 420 significantly reduced the increase in stomach permeability caused by the NSAID indomethacin in a study involving 120 male Wistar rats.

While the probiotic did not significantly protect against visual mucosal damage, it did lower the incidence of severe NSAID-induced lesions from 50% to 33%, suggesting a potential benefit in reducing serious gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifidobacterium animalis ssp. lactis 420 Protects against Indomethacin-Induced Gastric Permeability in Rats. Lyra, A., Saarinen, M., Putaala, H., et al.[2021]

The study found that non-digestible fractions of spent coffee grounds (hgf-NDSCG) can induce apoptosis in human colon cancer cells (HT-29) through mechanisms involving oxidative stress reduction, particularly influenced by the source of gut microbiota (lean vs. overweight).

Lean microbiota showed a lower lethal concentration (LC50) for hgf-NDSCG, indicating that the gut flora composition can significantly affect the chemopreventive efficacy of hgf-NDSCG against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota source impact in vitro metabolite colonic production and anti-proliferative effect of spent coffee grounds on human colon cancer cells (HT-29). Hernández-Arriaga, AM., Dave Oomah, B., Campos-Vega, R.[2019]

Bismuth preparations, such as tripotassium dicitrato bismuthate and bismuth subsalicylate, are safe for treating gastrointestinal disorders, with adverse reactions being mild and infrequent due to less than 1% systemic absorption of bismuth.

In clinical studies, even after repeated dosing, plasma bismuth concentrations remained well below toxic levels, indicating that these medications can be used effectively without significant risk of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: safety of bismuth in the treatment of gastrointestinal diseases. Tillman, LA., Drake, FM., Dixon, JS., et al.[2019]

The addition of bismuth subsalicylate to standard triple therapy for Helicobacter pylori infection resulted in a higher eradication rate of 89.7% compared to 80% in the placebo group, indicating its efficacy in treatment.

Patients receiving bismuth subsalicylate experienced fewer adverse effects, such as abdominal pain (20.7% vs. 52% in the placebo group) and no cases of dark feces in the placebo group, suggesting a safety advantage in using bismuth subsalicylate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Addition of bismuth subsalicylate to triple eradication therapy for Helicobacter pylori infection: efficiency and adverse events]. Hinostroza Morales, D., Díaz Ferrer, J.[2016]

Healthy women exhibit lower intestinal permeability and greater microbial diversity compared to men, indicating potential sex-based differences in gut health.

Both sexes experience increased intestinal permeability after taking indomethacin, but only women show a significant decrease in fecal microbial diversity, suggesting that women's gut microbiota may be more sensitive to disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota. Edogawa, S., Peters, SA., Jenkins, GD., et al.[2023]

In a study involving mice, the combination of high-fat diet (HFD) and altered colonic health from intrarectal capsazepine administration led to significant damage to the colonic mucosal lining and increased intestinal permeability over 8 weeks.

This damage prevented the protective effects of the prebiotic isomaltooligosaccharides, highlighting that the health of the colonic mucosa is crucial for the effectiveness of dietary interventions like prebiotics in mitigating HFD-induced harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capsazepine-Induced Altered Colonic Mucosal Health Limits Isomalto-oligosaccharide Action in High-Fat Diet-Fed C57BL/6J Mice. Kumar, V., Kumar, V., Kondepudi, KK., et al.[2023]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK560697/

Bismuth Subsalicylate - StatPearls - NCBI Bookshelf This educational activity focuses on bismuth subsalicylate's applications in managing gastrointestinal discomfort and traveler's diarrhea.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05930197

Effect of Bismuth Subsalicylate on the Gut Microbiome and ... 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 ...

3. gastrojournal.org gastrojournal.org/article/0016-5085(90)90983-8/fulltext

Bismuth therapy in gastrointestinal diseases Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8236042/

Systematic Review and Meta-Analyses Assessment of the ... The results show that subjects treated with bismuth subsalicylate for up to 21 days have 3.5 times greater odds of preventing travelers' ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2748049

Effect of Bismuth Subsalicylate vs Placebo on Use ... This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea.

6. mayoclinic.org mayoclinic.org/drugs-supplements/bismuth-subsalicylate-oral-route/description/drg-20068521

Bismuth subsalicylate (oral route) - Side effects & dosage Bismuth subsalicylate is used to treat diarrhea in adults and teenagers. It is also used to relieve the symptoms of an upset stomach, such as heartburn, ...

7. webmd.com webmd.com/drugs/2/drug-3596/bismuth-subsalicylate-oral/details

Bismuth subsalicylate (Kaopectate, Pepto-Bismol, and ... Bismuth subsalicylate is used to treat diarrhea and symptoms of an upset stomach, such as heartburn, indigestion, nausea, gas, burping, or fullness.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/2406853/

Bismuth subsalicylate: history, chemistry, and safety Neurotoxicity studies in animals and human safety data indicate that Pepto-Bismol can be used safely for its acute indications and for up to 3-4 weeks of ...

9. goodrx.com goodrx.com/bismuth-subsalicylate/what-is?srsltid=AfmBOoqF0-uiAuNQEUFUFtUVWx782DOruwWVQaeosfDlQaw_15tp3CKB

Bismuth Subsalicylate (Pepto-Bismol): Uses, Side Effects ... You shouldn't take bismuth subsalicylate (Pepto-Bismol) for more than 2 days. If you still have diarrhea or stomach problems after 2 days of taking the ...