Background Autoimmune gastritis is accompanied by severe gastric corpus atrophy and hypergastrinemia, and neuroendocrine tumor (NET) sometimes develops. We aimed to investigate changes in gastric mucosa-associated microbiota associated with the development of gastric NET in autoimmune gastritis.

Methods In a total of 19 patients diagnosed with autoimmune gastritis based on achlorhydria by 24 h impedance-pH monitoring examination, anti-gastric parietal cell antibody/anti-intrinsic factor antibody, and severe gastric corpus atrophy in upper gastrointestinal endoscopy at Osaka Metropolitan University Hospital, NET (+) group included patients who have developed NET (n=7) and NET (-) group included patients who have never developed NET (n=12). The control group included 11 patients diagnosed as H. pylori-uninfected. Bacterial DNA was enzymatically extracted from biopsy specimens of gastric mucosa, amplified by polymerase chain reaction using primers specific to the V3–V4 region of 16S rRNA, and analyzed using QIIME2^™.

Results The median tumor size of NETs was 5.5 mm (interquartile range, 4.5–6.0), 50.0% of lesions were located at the upper gastric body, and all lesions were NETG1 in WHO classification. In changes of microbial species in Fusobacteriota phylum, Fusobacterium nucleatum (p = 0.012) and Fusobacterium periodonticum (p < 0.001) were significantly increased in NET (+) group. In changes of microbial species in Proteobacteria phylum, Haemophilus parainfluenzae (p < 0.001), Haemophilus parahaemolyticus (p = 0.001), and Haemophilus haemolyticus (p < 0.001) were significantly increased in NET (+) group. In contrast, in changes of microbial species in Firmicutes phylum, Streptococcus salivarius (p < 0.001) and Veillonella atypica (p = 0.004) were significantly decreased in NET (+) group. Number of operational taxonomic unit was not significantly different between 3 groups. Alpha diversity (Faith’s phylogenetic diversity) was significantly higher in NET (+) group than in NET (-) group (p = 0.043). Beta diversity (weighted and unweighted UniFrac) was significantly different between NET (-) group and NET (+) group (p = 0.001).

Conclusions It was suggested that gastric mucosa-associated microbiota in patients with autoimmune gastritis who had developed gastric NETs may have changed compared to those who had not.