Risk of gastric neoplasms in autoimmune atrophic gastritis and its relationship with gastric microbiota and immune pathways

Autoimmune atrophic gastritis (AAG) is a slowly progressive organ-specific, immune-mediated condition, characterized by atrophy of the oxyntic mucosa with subsequent hypochlorhydria and hypergastrinemia. When this pathological process occurs, the subsequent reduced mass of specialized parietal cells can lead to impaired gastric acid and intrinsic factor secretion, eventually resulting in malabsorption of iron and vitamin B12 with consequent iron deficiency and/or pernicious anemia as well as an impairment of gastric microbiota composition and an increased risk of gastric tumours. The prevalence of AAG in the general population is estimated to be as high as 2-5%. Patients affected by AAG are likely to develop several neoplasms, in particular type-1 neuroendocrine tumors in percentage variable from 0.4% to 7% and gastric cancer (GC) with an incidence ranging between 0% and 1.8% per year. In AAG, the development towards GC depends on several factors such as conditions leading to an increased intragastric pH and oxidative stress, gastric microbiota composition, host factors such as the immune pathway, rather than environmental risk factors like smoke, alcohol, body mass index and diet. The increased GC risk associated to AAG emphasizes the importance of diagnosing and monitoring these patients, as recommended by the last European guidelines on diagnosis and management of precancerous gastric conditions (MAPS II). Many questions regarding the natural history of AAG and the risk factors for the development of GC in patients affected by AAG are still opened. On the basis of this scenario, several monocentric and multicentric studies were conducted within this PhD project with the aim to in-depth assess several clinical, biochemical, histological and immunological aspects, not previously investigated, that may contribute to better understand the natural history of AAG as well as the risk factors involved in gastric carcinogenesis and the best management of this gastric precancerous condition. Considering the studies performed on gastric microbiota and immunological pathways in AAG, we can consider them as the first pieces of evidence, and they certainly cannot be interpreted as a point of arrival but should rather be viewed as a starting point for future research in this very complex and intriguing field in which much work is yet to be done.