A recent scientific paper claims to have solved the decades-old mystery of how Helicobacter pylori causes ulcers and stomach cancer (Echizen et al., 2019; Science Daily 2019). H. pylori infection causes chronic inflammation, leading to proliferation of cells lining the stomach, which promotes gastric tumors. The Japanese scientists were able to identify and block the pathway that drives this inflammation, which prevented tumor formation in mice. Their anti-inflammatory drug approach has implications for both peptic ulcers and gastric cancer, which is the 4th most common cancer worldwide with the second highest mortality rate. All too often, it is chronic inflammation stemming from chronic infections that leads to cancer.

As for remedies, there are many drugs and nutrients that help reduce inflammation in the body. And I do believe that nutrition is the best way to prevent and treat ulcers and other chronic inflammatory conditions. Fish oil, vitamin E complex, ginger, turmeric, and aloe come quickly to mind, and there are many others. But the one drug that rivals these nutrients is bismuth (Bi). I have been studying it since the late 1980s. It is a naturally-occurring mineral in soil, used in a variety of industrial and medicinal processes.

Bismuth-containing drugs have been used for centuries for conditions like peptic ulcers, but only in the last few decades has it been taken seriously as an antimicrobial agent. Pepto-Bismol® (bismuth subsalicylate or BSS) has been shown to inhibit the growth of a wide spectrum of bacteria at doses achievable in the digestive tract. However, the inhibition is only a mild one, as it would not be prudent or healthy to strongly inhibit our friendly gut bacteria. What we discovered, back in the early 1990s, is that bismuth (Bi) has potent anti-slime activity (Domenico et al., 1991). We showed the same thing with salicylate (the active form of aspirin) a couple years earlier (Domenico et al., 1989). Together, they form BSS, and it is this dual anti-slime activity that makes it work so well for gut problems. Bismuth and salicylate were the first agents shown to inhibit slime production, and to work against many pathogens. The combined anti-slime effect of Bi and salicylate in Pepto-Bismol is additive and significant (inhibits >90% of slime) at the highest achievable doses.

Slime (a.k.a., biofilm) is a gooey substance that allows microbes to stick together and to stick to surfaces, such as on your teeth or in the toilet bowl. Slime allows the formation of large bacterial communities and confers resistance to noxious elements, such as antibiotics and immune defenses. Slime also absorbs large amounts of water and, like Jello, protects bacteria from drought. It also traps minerals and nutrients. Bacteria in slime can be dormant for months or years, waiting for an opportunity to infect when our defenses are down. Thus, slime is a camouflage, a cushion, a haven, and a reservoir all at once. No wonder it’s been around for 3.5 billion years and is so abundant in nature (Vidyasagar, 2016). The vast majority of medical device or foreign body infections result from biofilms, including intravenous, urinary and dialysis catheters, orthopedic prosthetic devices, shunts, pacemakers, stents, dentures, dental caries, periodontitis, breast implants, contact lenses, etc. Biofilm infections also include cystic fibrosis, COPD, UTI, endocarditis, otitis media, sinusitis, and diabetic wound infections (Wu et al., 2015). Biofilms enable bacterial persistence and pathogenicity in a variety of ways, and is implicated in the vast majority of bacterial infections, according to the National Institutes for Health (NIH). So, stopping slime is no small feat, and has the potential to solve many major unmet needs in medicine.

As its outermost layer, slime is how bacteria present themselves to their world. And, it is the primary target of host defenses. Once bacteria get into the bloodstream, several proteins attack the invaders, and white blood cells (WBCs) are called in to engulf and kill them. Once slime forms, bacteria grow too large and unappetizing for WBCs to eat. Unable to clear bacteria, the host must produce antibodies that help WBCs clear the infection. These antibodies attach directly to the slime to make bacteria easier targets. However, there are thousands of different types of slimes. Each slime is unique, and requires a unique specific antibody to neutralize it. An example of this is the pneumococcal polysaccharide (slime) vaccine, which contains slime from 23 different strep pathogens. If effective antibodies are generated early enough, tissue damage is minimized. In many instances, however, the elusive bacteria win out, either killing or damaging the patient. Thus, slime promotes infection by interfering with our basic defense mechanisms.

In modern times, doctors have relied heavily on antibiotics to treat infections caused by bacteria. However, slime producers are highly resistant to antibiotics. Anti-slime agents differ from antibiotics because they are more about prevention than about killing. They prevent bacteria (and some fungi) from sticking and waiting for a chance to infect. But removing slime also enables WBCs and antibiotics to kill bacteria by removing their armor. These anti-slime agents are inexpensive, broad spectrum, safe and thoroughly effective, which does not bode well for the profit-driven pharmaceutical industry.

Our group went on to invent a new class of anti-slime agents called bismuth thiols (BTs) that are 100s, if not 1000s, of times more potent than Bi and/or salicylate (Domenico et al., 1997; Domenico, 2015). That’s by virtue of the thiol group (a sulfur molecule with high affinity for metals like Bi), which facilitates Bi entry into bacterial cells. In contrast, Bi or BSS does not readily penetrate cells on its own. At very low and safe doses, BTs have the potential to eradicate most chronic infections (Domenico et al., 2000). They are currently approaching Phase 3 clinical trials for diabetic wound and orthopedic device infections, and are in the early stages of development for cystic fibrosis and other respiratory infections (www.microbioncorp.com).

Surprisingly, at even lower, microscopic doses, BTs have been shown to quell inflammation (Gluck et al., 1998a). We could reduce the mortality of septic mice by 60% with a single tiny intravenous dose of BTs. Since inflammation drives so many chronic diseases, and much of it stems from the gut, the anti-inflammatory properties of BTs (and maybe Pepto-Bismol) could prevent or lessen such diseases as cancer, circulatory disorders, diabetes, and the like. The anti-inflammatory activity of BTs stems from a different mechanism than its anti-slime properties (Gluck et al., 1998b; Saha et al., 2000; Barua et al., 2000), which is too complicated to describe here. It would make sense that Pepto-Bismol shares similar anti-inflammatory activity, given its soothing action on the gut. Certainly, salicylate has classic anti-inflammatory properties. Thus, prophylactic use of Pepto-Bismol might help more than just gut problems.

Bismuth has also been shown to reduce hydrogen sulfide gas in the gut, which is related to its anti-inflammatory activity. Excess hydrogen sulfide is implicated in gut disorders like SIBO (Irritable Bowel) and ulcerative colitis (Crohn’s). People with excess hydrogen sulfide gas to have their stools turn black when taking bismuth (Suarez et al., 1998).

We can then theorize that Pepto-Bismol works its wonders in myriad ways. And it has nothing to do with coating the stomach, as we’ve been told. Rather, it reduces slime buildup in the gut, which can reach toxic levels; and it might reduce inflammation produced by pathogenic bacteria encased in slime, as BTs do. No wonder it’s in the medicine cabinets of 60% of American households.

Echizen K, Horiuchi K, Aoki Y, et al. 2019. NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells. Oncogene. https://www.nature.com/articles/s41388-019-0702-0

Science Daily 2019. How inflammation causes gastric cancer. https://www.sciencedaily.com/releases/2019/04/190416094121.htm

Vidyasagar A. 2016. What Are Biofilms? LiveScience. https://www.livescience.com/57295-biofilms.html

Domenico P. 2015. Bismuth thiols as anti-biofilm agents. J Microbiol Exper 2(3):00049. http://medcraveonline.com/ JMEN/JMEN-02-00049.pdf

Domenico P, Schwartz S, Cunha BA. 1989. Reduction of capsular polysaccharide production in Klebsiella pneumoniae by sodium salicylate. Infect Immun 57(12):3778-82.

Domenico P, Landolphi DR, Cunha BA. 1991. Reduction of capsular polysaccharide and potentiation of aminoglycoside inhibition in Gram-negative bacteria by bismuth subsalicylate. J Antimicrob Chemother 28(6):801-810.

Wu H, Moser C, Wang H-Z, et al. 2015. Strategies for combating bacterial biofilm infections. Int J Oral Sci 7(1):1–7.

Domenico P, RJ Salo, SG Novick, PE Schoch, K Van Horn, BA Cunha. 1997. Enhancement of bismuth antibacterial activity with lipophilic thiol chelators. Antimicrob Agents Chemother 41:1697-1703.

Domenico P, Salo RJ, Cunha BA. 2000. The potential of bismuth-thiols for treatment and prevention of infection. Infect Med 17:123-127.

Gluck JA, Saha DC, Rackow EC, Astiz ME, Domenico P. 1998a. Effect of bismuth-thiol combination on survival in septic mice. Abstract, American Federation for Medical Research, Regional Meeting.

Gluck JA, Saha DC, Rackow EC, Astiz ME, Domenico P. 1998b. Effect of bismuth-ethanedithiol on reactive radical release by splenic macrophages in sepsis. Abstract, American Fed for Medical Research, Regional Meeting.

Saha DC, Shahin S, Rackow EC, Astiz ME, Domenico P. 2000. Cytokine modulation by bismuth-ethanedithiol in experimental sepsis. 10th Intl. Conf. Inflamm. Res. Assoc., Hot Springs, VA

Barua R, Shahin S, Hossain S, Rackow EC, Astiz ME, Domenico P, Saha DC. 2000. Bismuth-ethanedithiol modulates TNFa and IL-10 in septic mice. 10th Intl. Conf. Inflamm. Res. Assoc., Hot Springs, VA.

Suarez FL, Furne JK, Springfield J, Levitt MD. 1998. Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human colon. Gastroenterol 114(5):923-9.

One thought on “How Pepto-Bismol Works

  1. 9I couldn’t comment on your site unless login in to WordPress. I don’t have an account.)

    Very interesting, drwillip and great job explaining biofilms so clearly so everyone can understand it. Hope your group can bring this product to market soon so we can benefit from it!! Thank You

    On Thu, Apr 18, 2019 at 12:48 AM The Science of Nutrition wrote:

    > drwillip posted: “A recent scientific paper claims to have solved the > decades-old mystery of how Helicobacter pylori causes ulcers and stomach > cancer (Echizen et al., 2019; Science Daily 2019). H. pylori infection > causes chronic inflammation, leading to proliferation of ce” >

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