Gastric microbiome shifts linked to H. pylori-negative stomach ulcers in pilot study

Researchers have reported an association between alterations in the antral gastric microbiome and H. pylori-negative idiopathic gastric ulcers, in a prospective multicenter pilot study published in BMC Gastroenterology.

Between August 2022 and January 2024, the study enrolled 38 H. pylori-negative participants divided into three groups: a control group of 11 people who used NSAIDs but had no ulcer, a first case group of 21 people with active ulcers who had used NSAIDs for at least one month, and a second case group of six people with idiopathic ulcers, meaning active ulcers with no NSAID use.

Mucosal biopsies were taken from the antrum, the body of the stomach, the duodenal bulb and the second portion of the duodenum, and hypopharyngeal swabs were also collected. All samples were analysed using 16S rRNA sequencing processed through the QIIME 2 platform, allowing the team to profile which microbes were present and how their communities differed across sites and patient groups.

Clinical characteristics were generally comparable among the groups. The analysis found significant differences in antral beta-diversity, a measure of how microbial community composition differs between samples, in the idiopathic ulcer group. However, the authors note an important statistical caveat: significant PERMDISP results indicated that differences in within-group dispersion may have contributed to this pattern, meaning the compositional differences should be interpreted with caution rather than as a straightforward group separation.

Using age- and sex-adjusted ANCOM-BC2 analysis, the team identified multiple taxa-level differences in the idiopathic ulcer group, but the specific taxa identified were not fully consistent across analytical approaches. This inconsistency underscores the exploratory nature of the findings and the difficulty of pinning down individual bacterial species in a small pilot cohort.

One of the clearer signals emerged from gastrotyping of the antral microbiome. This approach suggested a two-cluster solution along a compositional gradient: one cluster characterized by relative predominance of Phocaeicola A and another dominated by Streptococcus. Ulcer patients, including both the NSAID-associated and idiopathic groups, showed a significantly higher representation of Cluster 1, the Phocaeicola A-predominant cluster, with a p-value of 0.044.

The authors are careful about what these results do and do not show. In their conclusions, they state that in this pilot study, alterations in the antral gastric microbiome were associated with H. pylori-negative idiopathic gastric ulcers. These are associations observed in a small sample, not evidence of causation, and the study was not designed to test whether microbial changes drive ulcer formation or result from it.

Several limitations follow from the study’s scale and design. With only six participants in the idiopathic ulcer group, estimates for that subgroup carry substantial uncertainty, and the observed PERMDISP findings complicate the interpretation of the beta-diversity results. The inconsistent taxa-level findings across analytical methods further limit how much weight can be placed on any single bacterial genus.

Despite these caveats, the researchers argue the findings justify further work. They describe the results as exploratory but say they support further investigation of the gastric microbiome in the pathophysiology of idiopathic gastric ulcer, and they emphasize that validation in larger independent cohorts is required before any firm conclusions can be drawn about the role of these microbial communities in ulcers that arise without H. pylori infection or NSAID use.

Subject of Research: Gastric mucosa-associated microbiome in H. pylori-negative gastric ulcer

Article Title: Gastric microbiome analysis in Helicobacter pylori-negative gastric ulcer: a prospective multicenter pilot study

Article References: Choi, S. I., Shin, C. M., Youn, Y. H., Shin, H., Kim, H. J., Park, C. H., Noh, D., Kim, G., Kim, S., Yang, H.-J., Kim, J. M., & Lee, D. H. (2026). Gastric microbiome analysis in Helicobacter pylori-negative gastric ulcer: a prospective multicenter pilot study. BMC Gastroenterology. https://doi.org/10.1186/s12876-026-05365-5

Image Credits: AI Generated

DOI: 10.1186/s12876-026-05365-5

Keywords: gastric microbiome, H. pylori-negative ulcer, idiopathic gastric ulcer, 16S rRNA sequencing, NSAID, antral beta-diversity, gastrotyping, pilot study, BMC Gastroenterology, mucosa-associated microbiome, Gastric, microbiome