Loss of Gastric Microbial Diversity and Vitamin-Related Metabolic Functions in Autoimmune Atrophic Gastritis and Gastric Neuroendocrine Tumors
Background Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by oxyntic mucosal atrophy, hypochlorhydria, and an increased risk of type I gastric neuroendocrine tumors (NET). This study aimed to characterize poorly understood gastric microbiome interactions, functional alterations and immune response in AAG and NET. Methods Gastric microbiome composition, predicted metabolic function, and immune responses were analyzed in 34 individuals, including patients with AAG (n = 15), gastric NETs (n = 8), and controls (n = 11). Gastric aspirates were examined using 16S rRNA gene sequencing. Microbial diversity, taxonomic composition, and inferred metabolic pathways were assessed. Peripheral blood mononuclear cells (PBMCs) were stimulated with heat-inactivated gastric bacterial preparations, and cytokine production was quantified using flow cytometry. Results The gastric microbiome showed progressive alteration from Controls to AAG and NET, with significantly reduced microbial richness and diversity, decreased evenness, and increased dominance in NET, while AAG displayed intermediate changes. Functional profiling demonstrated reduced microbial metabolic capacity, including pathways involved in vitamin and cofactor biosynthesis, consistent with impaired vitamin B12–related metabolic functions in AAG and NET. Gastric aspirate bacteria induced strong Th1 cytokine responses, with AAG-derived bacteria showing the greatest immunostimulatory activity. Conclusions AAG and gastric NET show overlapping gastric microbiome alterations, with greater loss of diversity and function in NET, depletion of vitamin and cofactor biosynthesis pathways linked to impaired vitamin B12 handling, and enhanced immunostimulatory potential that may contribute to gastric dysfunction and chronic immune activation.
Background Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by oxyntic mucosal atrophy, hypochlorhydria, and an increased risk of type I gastric neuroendocrine tumors (NET). This study aimed to characterize poorly understood gastric microbiome interactions, functional alterations and immune response in AAG and NET. Methods Gastric microbiome composition, predicted metabolic function, and immune responses were analyzed in 34 individuals, including patients with AAG (n = 15), gastric NETs (n = 8), and controls (n = 11). Gastric aspirates were examined using 16S rRNA gene sequencing. Microbial diversity, taxonomic composition, and inferred metabolic pathways were assessed. Peripheral blood mononuclear cells (PBMCs) were stimulated with heat-inactivated gastric bacterial preparations, and cytokine production was quantified using flow cytometry. Results The gastric microbiome showed progressive alteration from Controls to AAG and NET, with significantly reduced microbial richness and diversity, decreased evenness, and increased dominance in NET, while AAG displayed intermediate changes. Functional profiling demonstrated reduced microbial metabolic capacity, including pathways involved in vitamin and cofactor biosynthesis, consistent with impaired vitamin B12–related metabolic functions in AAG and NET. Gastric aspirate bacteria induced strong Th1 cytokine responses, with AAG-derived bacteria showing the greatest immunostimulatory activity. Conclusions AAG and gastric NET show overlapping gastric microbiome alterations, with greater loss of diversity and function in NET, depletion of vitamin and cofactor biosynthesis pathways linked to impaired vitamin B12 handling, and enhanced immunostimulatory potential that may contribute to gastric dysfunction and chronic immune activation.
Latvian Biomedical Research and Study Centre