Zhi Tong Zuo Department of Respiratory Disease, The Hospital Affiliated to Jiangnan University, China

Eradicating Helicobacter pylori bacterium increases the morbidities of asthma and other allergic diseases, according to existing epidemiological studies. Therefore, Zhi Tong Zuo and colleagues hypothesized that H. pylori might play a protective role against asthma.

For a paper published in the International Archives of Allergy and Immunology, Dr. Zuo and colleagues explored the possible protective influence of H. pylori on allergic asthma. “The incidence of H. pylori infection is decreasing in both adults and children in developed countries, while the incidence of asthma and other allergic disorders is increasing in children,” the study authors noted. “The ‘disappearing microbiota’ hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in early life, contributing to the development of some diseases. The ‘hygiene hypothesis’ links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent diseases.”

Eradicating H. pylori Is a Double-Edged Sword
H. pylori, Zuo and team noted, can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. H. pylori can also target dendritic cells (DCs) to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. H. pylori has also been shown to inhibit heat shock protein 70 (HSP70)—which might play a role in promoting asthma inflammation—and aid in the activation of Toll-like receptors (TLRs), which play a role in immune response. Furthermore, the gut-lung axis theory hypothesizes that the imbalance of intestinal flora is related to a variety of lung diseases, including asthma. Therefore, it is believed that the adjustment of intestinal flora can alleviate symptoms and reduce the incidence of asthma.

Eradicating H. pylori infection is considered a double-edged sword, the authors stated. “Eradicating H. pylori could decrease the occurrence of dyspepsia, peptic ulcer, and gastric malignancy,” they wrote. “However, there are concerns about the extensive application of eradication treatment, such as the resistance to antimicrobial agents and an increase in the prevalence of disorders that are negatively correlated with the infection of H. pylori, including obesity, asthma, GERD, and Barrett’s esophagus. Therefore, selective identification and elimination of only the virulent strains of H. pylori are significant in eradication therapy.” Exposure to H. pylori, particularly in childhood, could prevent asthma, epidemiology studies have shown. “Administrating an extract of H. pylori in a neonate (live bacteria are not involved) could prevent inflammation in the airway and metaplasia of the goblet cells,” explained Zuo and colleagues. “Injection of H. pylori extract could inhibit DCs in processing the allergen in the mediastinal lymph nodes and lungs. These results suggest that the extract of H. pylori following sensitization could effectively prevent allergic airway disorders.”

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In addition, H. pylori neutrophil-activating protein (HP-NAP), one of the main virulence factors of H. pylori, can also play a protective role in asthma by stimulating Th1 activation and attenuating Th2 response in allergic asthma. “Since HP-NAP is considered a possible regulator for Tregs and can inhibit allergic inflammation in asthma, it is possible to develop HP-NAP as an H. pylori-specific vaccine to treat allergic asthma,” the researchers noted. “Immunological methods can be used to design vaccines against infection, and it can also be used for the prevention of asthma.”

Therapies Derived from H. pylori Look Promising
For future research, Zuo and team would like to see the development of an effective vaccine that could be used by women before pregnancy, during pregnancy, or during breastfeeding to prevent asthma in infants via the placenta or breast milk.

H. pylori may protect allergic asthma by regulating the balance of Th1/Th2 and Thl7/Tregs, inhibiting DCs and HSP70, activating TLRs, and reducing gastroesophageal reflux, the study authors conclude. “The hygiene hypothesis, the disappearing microbiota hypothesis, and the gut-lung axis theory all support this protective effect,” they wrote. “Therapeutic products derived from H. pylori may be used to prevent and treat asthma. Specifically, perinatal exposure to H. pylori can reduce allergic airway inflammation in the offspring, which also provide a new insight for interventional treatment of asthma and the possible application of H. pylori in treating asthma.”