Microbiome changes in the gastric mucosa and gastric juice in different histological stages of -negative gastric cancers.

BACKGROUND

The gastric microbiota in patients with gastric cancer (GC) has received increasing attention, but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood, especially for patients with -negative GC (HPNGC).

AIM

To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.

METHODS

The 16S rRNA gene analysis was performed on gastric mucosa from 134 -negative cases, including 56 superficial gastritis (SG), 9 atrophic gastritis (AG), 27 intestinal metaplasia (IM), 29 dysplasia (Dys), and 13 GC cases, to investigate differences in gastric microbial diversity and composition across the disease stages. In addition, paired gastric mucosa and juice samples from 18 SG, 18 IM, and 18 Dys samples were analyzed. α-Diversity was measured by Shannon and Chao1 indexes, and β-diversity was calculated using partial least squares discrimination analysis (PLS-DA). Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.

RESULTS

The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis. The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group, and the patients with GC had the lowest bacterial community richness ( < 0.05). Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with and as the predominant genera. Microbial network analysis showed that there was increasing correlation strength between IM and Dys (|correlation threshold|≥ 0.5, < 0.05). GC and its precancerous lesions have distinguishable bacterial taxa; our results identified HPNGC-associated bacteria and ( < 0.05). Additionally, across precancerous lesion stages from AG to Dys in -negative patients, abundance continuously increased, while and abundance presented a continuous downward trend. Furthermore, the microbial diversity was higher in gastric juice ( < 0.001) than in the mucosa, while PLS-DA revealed a statistically significant difference between the two groups (ANOSIM, = 0.001). A significant difference in the microbial structure was identified, with being more prevalent in the gastric mucosa and being more abundant in gastric juice.

CONCLUSION

Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.