Changes in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the changes in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer. Methods: The systematic review was performed based on a published protocol. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (February 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both gastric cancer and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD). Findings: Our systematic review included 742 gastric cancer patients and 765 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer OTUs (MD=-62.84, 95%CI: -123.43 to -2.25) and a lower Simpson index (MD=-0.13, 95%CI: -0.20 to -0.07) compared with non-cancer group. At the phylum level, gastric cancer group had lower abundance of Proteobacteria (MD=-15.94, 95%CI: -31.44 to -0.44) while higher abundance of Firmicutes (MD=7.48, 95%CI: 2.49 to 12.47). At the genus level, Streptococcus (MD=3.00, 95%CI: 0.07 to 5.93), Lactobacillus (MD=5.76, 95%CI: 0.74 to 10.79) and Veillonella (MD=1.04 95%CI: 0.07 to 2.00) were found to be enriched in gastric cancer group. Interpretation: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered. Funding: This work was supported by Peking Union Medical College Hospital Youth Program (grant number pumch201911356), Beijing Science and Technology Program（grant number 181100001618013） and National Key Technology Research and Development Program (grant number 2016YFC1302802). Declaration of Interest: None declared