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A Pig for Peptic Ulcers

Posted by Richard Conniff on September 26, 2013

Readers may remember that there’s been a lot of controversy recently about the bacteria species Helicobacter pylori.  Here’s what I wrote about it, in a feature on the microbiome earlier this year in Smithsonian:

For Blaser, the decline of one “bad” bacterial species represents what’s happening to the entire microbiome.   Helicobacter pylori, which lives in the human stomach, became notorious in the 1980s after University of Western Australia scientists Barry Marshall and Robin Warren demonstrated that it is the essential precondition for almost all gastric ulcers.   The microbe was already on the decline from sanitary improvements and routine antibiotic use, but doctors then began directly targeting H. pylori in adults, incidentally meaning parents were less likely to pass the microbe on to their children. Today, while up to 100 percent of children in developing countries have Helicobacter, fewer than 20 percent of kids in some developed countries do —and the latter is ostensibly a good thing.)

“It’s good and it’s bad,” says Blaser.  A study last year traced the human association with H. pylori back at least 116,000 years into our evolutionary history.  “The idea that an organism that has been with us that long is disappearing in a century is striking,” says Blaser.  “The good news is that it means less ulcers and less gastric cancer.  The bad news is that it means more childhood-onset asthma and more esophageal reflux, both of which have been linked to a lack of Helicobacter.”  In certain circumstances, Blaser argues, H. pylori may have protective effects we don’t yet fully recognize.

The medical community has thus far resisted the rehabilitation of H. pylori …

So now there’s a pig bred to serve as a model for better research on how H. pylori or harms. Here’s the press release:

Researchers at the Virginia Bioinformatics Institute at Virginia Tech have developed a new large animal model to study how the immune system interacts with the stomach bacterium Helicobacter pylori, the leading cause of peptic ulcer disease.

The discovery in the October edition of the journal Infection and Immunity may inform changes in the ways doctors treat patients. An estimated 4 million Americans have sores in the stomach lining known as peptic ulcers, according to the American Gastroenterological Association.

Although the bacterium is found in more than half the world’s population, most people do not develop diseases. However, some experience chronic inflammation of the stomach, or gastritis, which can lead to the development of ulcers or cancer.

In addition to its role as a pathogen, the bacteria have beneficial effects, preventing certain chronic inflammatory and metabolic diseases, including Type 2 diabetes, and obesity.

When bacteria reside within host cells, the immune system typically recruits a type of white blood cell called T cells — in this case, CD8+ cytotoxic T cells — to destroy the infected cells.

However, the researchers found that these cells may contribute to tissue damage.

In patients with H. pylori-associated gastritis, higher numbers of cytotoxic T cells are present, indicating that these cells may contribute to the development of gastric lesions.

To study immune responses in H. pylori-mediated disease, researchers at the Virginia Bioinformatics Institute’s Nutritional Immunology and Molecular Medicine Laboratory developed a pig model that closely mimics the human gastric environment. When pigs were infected with H. pylori, the researchers observed an increase in another type of immune cells called pro-inflammatory CD4+ T helper cells, followed by an increase in CD8+ cytotoxic T cells, according to the study.

Scientists did not observe an increase in CD8+ T cells in mouse and gerbil models of H. pylori infection. However, the rise of the cells in pigs mirrors the recent findings in human clinical studies.

“Pigs have greater anatomic, physiologic and immunologic similarities to humans than mice, the main animal model used in biomedical research,” said Raquel Hontecillas, co-director of the Nutritional Immunology and Molecular Medicine Laboratory and the Center for Modeling Immunity to Enteric Pathogens. “The results from our new pig model closely mimic what has been reported in clinical settings, which will allow us to comprehensively and systematically investigate human immune responses to H. pylori.”

The discovery will help scientists better understand the complex interactions of H. pylori and its host.

Researchers within the Center for Modeling Immunity to Enteric Pathogens are using results from the pig model and other experimental data to develop a computational model of H. pylori infection. Such modeling efforts aim to develop faster, more efficient ways to predict initiation, progression and outcomes of infection.

The Center for Modeling Immunity to Enteric Pathogens is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under Contract No. HHSN272201000056C. PI: Josep Bassaganya-Riera

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