SIGNIFICANT spatial heterogeneity of microbial diversity has been demonstrated in gastric cancer tissues, showing that oral-associated microbiotas, particularly in the upper third of the stomach, serve as an independent prognostic factor for overall survival. Gastric microbiotas play a vital role in the development of gastric cancer. In particular, Helicobacter pylori has been associated with non-cardia gastric cancer. Researchers aimed to analyse the spatial heterogeneity of the microbial diversity of gastric cancer and construct a co-occurrence network of oral-associated microbes that interact with H. pylori in patients with gastric cancer.
A multicentre retrospective analysis was conducted on 223 patients with gastric cancer who had undergone a gastrectomy. Dental plaque, tumoral tissue, and paired adjacent non-tumoral tissue samples were collected and sequenced, and the prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays. Gastric samples with ≤1% H. pylori relative abundance were defined as H. pylori-negative, while gastric samples with >1% H. pylori relative abundance were H. pylori-positive. It was determined that 168 patients were H. pylori-positive, 111 of whom had gastric cancer in the lower third of the stomach.
The analysis revealed a significant overall difference in beta diversity according to Bray-Curtis dissimilarity between tumoral and non-tumoral tissue (p= 0.005), and the microbiomes of the tumoral tissue group had significantly greater Shannon-estimated microbial richness (p=0.0002346). In particular, Veillonella parvula (p=0.0098), Streptococcus oralis (p= 0.0034), Streptococcus anginosus (p =0.0006), and Prevotella intermedia (p= 0.0430), were enriched in gastric tumoral tissues. Whereas, the relative abundance of H. pylori was significantly greater in nontumoral tissue (p= 0.0001). The researchers concluded that H. pylori was more abundant in the lower third of the stomach, whereas co-occurring oral-associated microbiota clusters, including V. parvula, S. oralis, S. anginosus, and P. intermedia, were more abundant in the upper third.
A higher microbial abundance in tumour tissues was associated with greater overall survival (p=0.0113, hazard ratio [HR]: 2.2528; 95% confidence interval [CI]: 1.265–6.010) and a greater benefit from chemotherapy (p= 0.0189, HR = 2.773, 95% CI:1.251–10.12). The research team also revealed that H. pylori-negative patients with oral-associated gastric microbiota showed worse overall survival.
In conclusion, the study demonstrates that oral-associated microbiota, including Veillonella parvula and Streptococcus oralis, are significantly enriched in the upper third of the stomach of patients with gastric cancer, and these species are correlated with overall survival. This highlights a potential avenue for a non-invasive screening and prognostic tool, especially for H. pylori-negative cases.
Katrina Thornber, EMJ
Reference
Lei L et al. Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer. mSystems. 2024;9(7):e0008924.
