Introduction: Helicobacter pylori is most frequently linked to gastric adenocarcinoma (GC). However, other bacteria may also play a role in gastric carcinogenesis. We aimed to identify what bacteria are significantly linked to GC in a high-risk ethnic Chinese community through a microbiota survey. Given the consistent enrichment of lactic acid bacteria (LAB) observed in GC, we next sought to evaluate, for the first time, the true pooled impact of three LAB associated with GC, Lactobacillus, Streptococcus, and Peptostreptococcus, on gastric precancerous lesions (GPLs) and GC, through a meta-analysis.
Methods: Gastric biopsies from 17 GC cases and 155 functional dyspepsia (FD) controls were processed to examine the gastric microbiota using 16S rRNA gene (DNA) and transcript (cDNA) amplicon sequencing of the V4 region with Illumina MiSeq 2x250 bp chemistry. For the meta-analysis, a comprehensive literature search was performed on PubMed, Scopus, and Science Direct. Data on mean relative abundance (%), standard deviation, and demographic characteristics, were collected from 20 studies (GC = 14 and GPL = 15). Statistical analyses included pooled effect size estimation under the random effects model, publication bias (Egger's regression and funnel plots), heterogeneity (Cochran's Q and Higgin's I2 tests), and sensitivity analyses.
Results: The gastric microbiota composition and alpha diversity of GC differed considerably from that of FD subjects. The relative abundance of Lactobacillus was significantly higher in GC across all analyses, independently of H. pylori status, in both DNA and cDNA subgroups. The meta-analysis, comprising 1298 subjects, revealed the pooled mean relative abundance of LAB was significantly increased in cases (GPLs+GC) compared to controls (p = 0.040). In particular, Lactobacillus pooled mean relative abundance was significantly higher in GC (p <0.001) and dysplasia (p = 0.014) patients compared to controls from high GC risk populations.
Conclusions: There is significant enrichment of Lactobacillus in GC, which has been validated through a comprehensive and stringent meta-analysis, indicating that this is an important dysbiotic signature of gastric carcinogenesis. Given that Lactobacillus spp. produce large amounts of the oncometabolite lactate, this requires further investigations.