The significance of the gram-negative, microaerophilic, spiral bacterium Helicobacter pylori (Hp) in the formation of gastric and duodenal diseases now widely recognized, and it is no longer necessary to explain it. J Robin Warren and Barry Marshall were awarded the Nobel Prize in Physiology or Medicine in 2005 for establishing the importance of this bacterium, which is significantly involved in gastric and duodenal ulcers. Dr. Marshall even appeared in a TV commercial that is broadcast in Japan, discussing a Meiji Dairies yogurt containing one of the lactobacilli (i.e. LG20) targeting the reduction of Hp. The Hp-based eradication of chronic gastritis has begun to be covered by the national health insurance system through the efforts of the Helicobacter Society of Japan, and approx. 1 million people receive eradication treatment each year in Japan. Gastric cancer caused by Hp may eventually become a rare disease even in Japan and east Asian countries, where gastric cancer remains a common cause of death.
However, in daily medical care, many physicians have encountered patients in whom chronic gastritis is revealed by gastroscopy, but Hp is not detected even after various tests. I have the impression that this type of case is gradually increasing now that Hp eradication has become commonplace. A polymerase chain reaction (PCR) test revealed that these cases contained a significant proportion of non-Helicobacter pylori Helicobacter species (NHPH), which are the subject of this book.
NHPH is included in the same genus as Hp, but has some characteristics that differ from those of Hp. Especially in terms of diagnosis, the diagnostic method that applies urease, which is widely used for Hp, often does not give a positive result for NHPH, thus overlooking these bacteria. In addition, NHPH are found not only in the mucous layer of the stomach but also in the gastric glands, especially in the intracellular canaliculus and cytoplasm of the acid-secreting parietal cells. Dogs, cats, pigs, and other non-human species are the main natural hosts of NHPH, presenting a zoonotic infection pattern. It is thus expected that the ratio of NHPH infections will increase, now that the number of people who are Hp-positive continue to decreases due to the above-mentioned eradication, and the natural hosts of NHPH bacteria can be expected to transmit to these bacteria.
In 2010, with a grant from the Helicobacter Society of Japan, our research group began to investigate cases all over Japan by the PCR method, and we observed that a high percentage of individuals with mucosa-asssociated lymphoid tissue (MALT) lymphoma who were negative for Hp, nodular gastritis, and chronic gastritis were positive for NHPH. These data were reported to Helicobacter (Journal) in 2020. In recent years, as with Hp, the culturing of bacteria from biopsy tissues of dogs, cats, and humans -which was not possible in the past- has been succeeded and the whole genome analyses of NHPH have become possible. The precise infection status of each NHPH and its pathogenic factors are expected to be revealed in the near future.
In this book, we summarize or group' research history first as dialogue, and we then clarify the present challenges. The history of the research of NHPH in connection with Hp, its biology and the relation to diseases are then discussed.