Helicobacter Pylori Gastric Ulcers and Cancer

Stomach Pathogen or Immune Regulator?

Helicobacter pylori (Hp) has co-evolved with the human stomach.  Hp has always been passed from mother to child as the child started premasticated solid foods.  The advent of processed baby foods and antibiotics has eliminated Hp in 90% of the US population and coincides with a dramatic rise of allergies, asthma and autoimmune diseases (commonly explained by the hygiene hypothesis.)

Hp Is Stomach-Adapted

Hp is adapted for growth in an acidic environment.  It produces ammonia to neutralize stomach acid. It also provided me with great perplexity in searching for heparin-binding domains in Hp proteins suspected of binding to stomach epithelial cells.  I generalized that pathogens must have proteins on their surfaces that bind to the heparan sulfate proteoglycans of epithelial cells.  I checked candidate Hp proteins and found histidines where I expected to find basic amino acids, either lysine or arginine.  The “duh” moment came when I realized that the pH of the Hp milieu was acidic and hence histidine would have a positive charge and function like the other two basic amino acids.  Hp was adapted to its stomach world.

Is Hp Good or Bad?

I have been trying to incorporate Hp as a pathogen into my view of gut function.  After all, Hp causes stomach ulcers and gastric cancer.  Several studies over the last few years have shown an association between Hp and asthma, but it is a negative association.  Hp seems to provide protection from asthma and I think that it is likely that the protection extends to allergies and autoimmune diseases.  It is also noteworthy that analysis of genetic predisposition to gastric cancer only reveals polymorphism in genes associated with inflammation, e.g. IL-1 or TNF.

Hp Lives on Hydrogen from Gut Biofilms

Further evidence of the integral nature of Hp as part of the natural gut flora is its use of molecular hydrogen (H2) as an energy source, i.e. high energy electrons for its electron transport chain to produce ATP or to power membrane transport.  The source of the hydrogen is Klebsiella in biofilms in the intestines.  The hydrogen diffuses into the intestinal blood supply and is circulated to the stomach lining where it provides energy for Hp.  Attacking gut biofilms may starve Hp and feeding starch (indigestible branch oligosaccharides are unique food source only accessed by Hp pullulanase) enhances Hp hydrogen nutrients.  [Since regulation of the Hp genes is not thoroughly understood, it is also possible that ample starch could shut down nitrogenase and starve the Hp.]

Hp Increases Tregs

Allergies and autoimmune diseases point to problems in self/non-self recognition, i.e. immunological tolerance.  And tolerance is dependent on regulatory T cells.  In this context, it is interesting that Hp stimulates the accumulation of regulatory T cells.  The gut is the major repository of cells of the immune system.  It seems to follow that by elimination of the stomach Treg population by curing Hp infections, the body may be deprived of it major resource to suppress immunological responses to innocuous antigens in foods, pollens, etc. and to self antigens.  Coupling a shortage of Tregs with chronic inflammation may lead to allergies and autoimmune diseases.  Another source of Treg depletion that may further compromise the immune system is circulating LPS, endotoxemia, that is associated with obesity (and leaky gut?)