“To gastroenterologists, the concept of a germ causing ulcers was like saying that the Earth is flat."
- Barry Marshall, M.D., Professor of Clinical Microbiology, University of Western Australia, 2005 Nobel Laureate
“We’re talking about a bug [Helicobacter pylori] that’s been in the gut for at least 58,000 years. There’s probably a reason for that.”
- Martin Blaser, M.D., Director, Center for Advanced Biotechnology and Medicine, Rutgers University
For decades, the medical community believed that psychological stress and too much stomach acid caused peptic ulcer disease. Then in 1982, Barry Marshall and J. Robin Warren, two Australian physicians, proved that the bacterium Helicobacter pylori is the cause of most peptic ulcers. In 2005, the Nobel Committee awarded them the Nobel Prize for Physiology or Medicine for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.”
While H. pylori is the bacterium that causes peptic ulcer disease and most stomach cancers, it has been hypothesized that it also protects us against certain inflammatory diseases. In this week’s Germ Gems post, I focus on the two faces of H. pylori—the known evil and the hypothesized good.
The evil face of H. pylori. H. pylori is a Gram-negative spiral bacterium that, along with about 35 other species, belongs to the genus Helicobacter. H. pylori, however, is the most widely known species. It infects more than one-half of the world population and nearly one-third of Americans. In addition to its role in peptic ulcers and gastritis, it is the cause of most stomach cancers and of gastric mucosa-associated lymphoid tissue lymphoma (MALT) prompting the World Health organization to classify H. pylori as a top carcinogen.
H. pylori has the amazing capacity to survive in the very acidic mammalian stomach by producing large amounts of the enzyme urease, which raises the local pH from about 2 to a more compatible range of 6 to 7. Because of its tolerance to acid, it lives happily in the lining of the upper gastrointestinal tract, where in most cases, it doesn’t cause any symptoms. But some strains of H. pylori are pathogenic and are strongly associated with peptic ulcers, chronic inflammation of the stomach (gastritis) and duodenum (duodenitis), and with stomach cancer.
Though human-to-human spread is thought to occur through gastro-oral, oral-oral, or fecal-oral routes, the predominant mode of transmission of H. pylori is unknown. Despite advances in hygiene, H. pylori infection continues to be a large burden in much of the world. Living in a developing country, in crowded conditions, or without a reliable supply of clean water all increase the risk of H. pylori infection in children.
Management of H. pylori infection. Most people with H. pylori infection never have any signs or symptoms. When they do, such symptoms are typically related to gastritis or peptic ulcer and may include an aching or burning pain in the abdomen, nausea, loss of appetite, frequent burping, bloating, unintentional weight loss, bloody or black tarry stools, bloody or black vomit that looks like coffee grounds.
The American College of Gastroenterology and the Infectious Diseases Society of America provide detailed guidelines for the diagnosis and treatment of H. pylori infection. Primary healthcare providers, often with the input of a gastroenterology consultant, provide recommendations regarding the best treatment, as well as the choice of diagnostic tests (e.g., urea breath tests, fecal antigen tests, or endoscopy with mucosal biopsy). Treatment usually consists of a proton-pump inhibitor to suppress acid production and two or three antibiotics. (Bacteria belonging to the genus Helicobacter are usually susceptible to antibiotics.) The most important antibiotics are clarithromycin, metronidazole, and amoxicillin. Bacterial resistance to these agents, however, is an increasing problem worldwide and complicates the management of the infection. (Emergence of antibiotic resistance isn’t unique to H. pylori. I’ve addressed this global crisis in previous Germ Gem posts, most recently on April 13, 2022 in “Antimicrobial Resistance: the Elephant in the Pandemic Room.”)
The good face of H. pylori? In the late 1990s, Dr. Martin Blaser, an infectious diseases expert and authority on the human microbiome, proposed that the eradication of non-pathogenic strains of H. pylori from the gastrointestinal tract by antibiotics could lead to a number of human ailments. He hypothesized that some stains of H. pylori confer protection against diseases such as gastroesophageal reflux (GERD), Barrett’s esophagus, and cancer of the esophagus. He stated, “We have focused on H. pylori because we have the diagnostic test to detect it, but you could say H. pylori is an indicator organism for what is probably a vast and disappearing microbiota and increasing disease risk.” His landmark hypothesis was described in the June 1999 Journal of Infectious Diseases’ article “Hypothesis: The Changing Relationships of Helicobacter pylori and Humans: Implications for Health and Disease,” and more broadly in his book Missing Microbes.)
In 2015, researchers at the University of Nottingham conducted a comprehensive analysis of the literature of a large number of studies that linked H. pylori infection with a reduced risk of developing extra-gastric conditions, such as, allergy, asthma, inflammatory bowel disease, celiac disease, and multiple sclerosis. In their article “Helicobacter pylori-Mediated Protection against Extra-Gastric Immune and Inflammatory Disorders: The Evidence and Controversies,” published on-line in the open access journal, Diseases, they reported their results concluding that the evidence supporting the putative protective effects of H. pylori was weak or inconclusive.
While the University of Nottingham’s study does not provide support for Dr. Blaser’s hypothesis, it doesn’t disprove it. And it is important to note that coincident with Blaser’s hypothesis in 1999, the field of the “Human Microbiome” emerged.
We now know that the human gut contains about 40 trillion bacteria belonging to an estimated 2,000 species, of which H. pylori is but one. Thus Dr. Blaser’s warning that the elimination of H. pylori by antibiotic treatment could result in an increased risk of GERD or other medical disorders, is still relevant. It may not reflect, however, only the eradication of friendly strains of H. pylori but of other non-pathogenic (protective) bacterial species as well.
Future considerations. One thing the studies of H. pylori do make clear is this: we must be judicious in our use of antibiotics. Always discuss with your medical provider the pros and cons of taking an antibiotic—it could destroy the friendly germs in your microbiome that are protecting you against one or more of the inflammatory diseases that Dr. Blaser worried about.
INTERESTING ESSAY