Oral and gastric microbiome in relation to gastric intestinal metaplasia

Abstract

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Keywords: case-control study; gastric intestinal metaplasia; gastric microbiome; oral microbiome; shotgun metagenomic sequencing.

Figure 1.

Oral and gastric taxa associated with gastric intestinal metaplasia. Forest plot of odds ratios (ORs) and 95% confidence intervals (95% CI) for associations between clr-transformed taxa relative abundance and gastric IM in standard conditional logistic regression models. These taxa in both the oral and gastric microbiota were consistently associated with gastric IM.

Figure 2.

Pathways in the oral microbiome associated with gastric intestinal metaplasia. (A) Forest plot of odds ratios (ORs) and 95% confidence intervals (95% CI) for associations between clr-transformed pathway relative abundance and gastric IM in standard conditional logistic regression models. (B) Correlations between IM-associated oral species and functional pathways. Spearman correlation coefficient values were estimated for each pairwise comparison of clr-transformed species and pathway relative abundance. Here we show only species in Table 2 and Figure 1 with known contribution to each pathway according to the species-specific pathway data.

Figure 2.

Pathways in the oral microbiome associated with gastric intestinal metaplasia. (A) Forest plot of odds ratios (ORs) and 95% confidence intervals (95% CI) for associations between clr-transformed pathway relative abundance and gastric IM in standard conditional logistic regression models. (B) Correlations between IM-associated oral species and functional pathways. Spearman correlation coefficient values were estimated for each pairwise comparison of clr-transformed species and pathway relative abundance. Here we show only species in Table 2 and Figure 1 with known contribution to each pathway according to the species-specific pathway data.

Figure 3.

Pathways in the gastric microbiome associated with gastric intestinal metaplasia. (A) Forest plot of odds ratios (ORs) and 95% confidence intervals (95% CI) for associations between clr-transformed pathway relative abundance and gastric IM in standard conditional logistic regression models. (B) Correlations between IM-associated gastric species and functional pathways. Spearman correlation coefficient values were estimated for each pairwise comparison of clr-transformed species and pathway relative abundance. Here we show only species in Table 3 and Figure 1 with known contribution to each pathway according to the species-specific pathway data.

Figure 3.

Pathways in the gastric microbiome associated with gastric intestinal metaplasia. (A) Forest plot of odds ratios (ORs) and 95% confidence intervals (95% CI) for associations between clr-transformed pathway relative abundance and gastric IM in standard conditional logistic regression models. (B) Correlations between IM-associated gastric species and functional pathways. Spearman correlation coefficient values were estimated for each pairwise comparison of clr-transformed species and pathway relative abundance. Here we show only species in Table 3 and Figure 1 with known contribution to each pathway according to the species-specific pathway data.