Blaser is best known for his studies of
Helicobacter pylori and its relationship with human diseases. Initially skeptical of Nobel laureate
Barry Marshall's findings of ''H. pylori's'' relationship to gastric and peptic ulcers, which Blaser described as "the most preposterous thing I'd ever heard; I thought, this guy is a madman," Blaser's work nonetheless later helped establish the role of
H. pylori in the causation of gastric cancer, the second leading cause of cancer death in the world. Studies of the diversity of
H. pylori lead him to identify the
CagA protein and its gene in 1989, which broadened understanding of
H. pylori interactions with humans. His team found that
cagA+ strains induced enhanced host responses, development of atrophic gastritis, gastric cancer, and peptic ulcer disease, compared to
cagA− strains, and that
cagA+ strains signal human gastric cells differently from
cagA− strains, and affect gastric physiology in markedly different ways than in the absence of
H. pylori. and also for the relationship of persisting microbes to cancer, and age-related mortality. Beginning in 1996, he hypothesized that
H. pylori strains might have benefit to humans as well as costs. Despite considerable and ongoing skepticism by the community of
H. pylori investigators, Blaser and his colleagues progressively developed a body of research that provided evidence that gastric colonization by this organism provided protection against the esophageal diseases of gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal adenocarcinoma, work that has since been confirmed by independent investigators. His work has suggested a benefit of
H. pylori against such early life illnesses as childhood diarrhea and asthma. This work is consistent with the hypothesis that
H. pylori is an ancient, universal inhabitant of the human stomach that has been disappearing as a result of 20th century changes in socio-economic status, including the use of antibiotics and that this loss has health consequences, not only good (less gastric cancer), but bad as well (more esophageal disease and cancer, and more childhood-onset allergic asthma and hay fever). In 1998, Blaser created the term acagia, to indicate a susceptibility for esophageal diseases in persons not carrying
cagA+
H. pylori strains. Since then, acagia has come to reflect the rise in other diseases associated with the loss of
cagA+
H. pylori, and may become a metaphor for the disappearance of members of the human microbiome that have symbiotic roles. He envisioned a step-wise (generational) diminution in microbial diversity, especially in early life to explain the epidemic rise of such diseases as childhood-onset asthma and obesity. Blaser has proposed that greater understanding of our indigenous (and progressively disappearing) microbiota can lead to improvements in human health. He has proposed that the routine use (and overuse) of antibiotics in young children may be causing collateral damage, with extinctions of our ancient microbiota at critical stages of early life. This scenario may be contributing to the risk of epidemic metabolic, immunologic, and neurodevelopmental disorders. and on-going work in children with reference to many diseases, including asthma, show the importance of early life microbiome perturbation in increasing risk. Studies with colleagues at the Mayo Clinic have shown a strong association of antibiotic exposure before the age of two and the development of multiple conditions in later childhood, including asthma, eczema, overweight and obesity, ADHD, and learning disability, providing further support for his hypothesis. Studies with colleagues examining data from children in Denmark and England confirm the Mayo Clinic findings. His studies in mice provide evidence that the effects of antibiotic perturbation on the
microbiota can be transmitted via the mother to the next generation, affecting both intestinal micro-ecology and disease manifestations. In recent studies, he has shown that antibiotic-induced microbiota perturbation leading to disease (Type 1 diabetes) in an experimental mouse model can be interdicted by subsequent exposure of young animals to maternal cecal contents; this work provides evidence and a proof-of-principle that the antibiotic-induced dysbiosis can be limited by restorative practices. ==
Missing Microbes==