Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion

Abstract

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

Keywords: Autoimmune gastritis; Gastric cancer; Type 1 neuroendocrine tumors; Helicobacter pylori; Streptococcus anginosus; Intestinal metaplasia

Core Tip: Autoimmune gastritis (AIG) is associated with a lower risk of gastric cancer than expected due to the low prevalence of precancerous lesions. In contrast, the risk of type 1 neuroendocrine tumors (Type1-NETs) is high and always co-exists with anti-parietal cell antibodies and extensive oxyntic atrophy. Endoscopic surveillance is needed for the early diagnosis and curative treatment of Type1-NETs. The progression of gastric atrophy during the course of AIG leads to hypochlorhydria and subsequent changes in the gastric microbiome. Among the numerous species harboring the stomach in patients with atrophic AIG, Streptococcus anginosus is one of the key candidates to be a driver of gastric carcinogenesis in post- Helicobacter pylori era.