Effect of Helicobacter Pylori Eradication on Human Gastric Microbiota: A Systematic Review and Meta-Analysis.

Background: Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer and eradication of H. pylori is recommended as an effective gastric cancer prevention strategy. The infected individuals show microbial dysbiosis of gastric microbiota. In recent years, agrowing number of studies have focused on gastric microbiota changes following H. pylori eradication. In the present study, we aim to evaluate the influence of successful H. pylori eradication on the short-term and long-term alterations of human gastric microbiota using a method of systematic review and meta-analysis. Methods: We did a systematic search based on three databases (PubMed, EMBASE, and Web of Science) in November 2021. Additional articles were also identified by reviewing references cited in the included papers. Human studies that reported changes in gastric microbiota following successful H. pylori eradication were enrolled. PROSPERO registration number: CRD42021293796. Results: In total, nine studies enrolling 546 participants were included. Regarding quadruple therapy, alpha diversity indexes increased within 1 month after eradication; significant differences in gastric microbial community structure between before and after eradication were also seen within 1 month. The trends of the above-mentioned diversity changes persisted with a follow-up of 6 months. The microbial composition altered significantly after eradication and the relative abundance of H. pylori-related taxa decreased. Accordingly, gastric commonly dominant commensals were enriched. Bioinformatic analyses of microbiota functions showed that bacteria reproduction-related pathways were down-regulated and pathways of gastric acid secretion, etc. were up-regulated. For triple therapy, similar trends of alpha diversity and beta diversity changes were observed in the short-term and long-term follow-up. Also, after eradication, H. pylori was not the gastric dominant bacteria and similar changes in gastric microbial composition were found. For gastric microbial interactions, a decrease in microbial interactions was seen after eradication. Additionally, regarding whether successful H. pylori eradication could restore gastric microbiota to uninfected status, the results remain controversial. Conclusion: In conclusion, successful H. pylori eradication could reverse the gastric microbiota dysbiosis and show beneficial effects on gastric microbiota. Our findings may provide new insight for exploring the role of H. pylori and the whole gastric microbiota in gastric carcinogenesis.

Type 1 interferon aggravates lipopolysaccharide-induced sepsis through upregulating Caspase-11 and Gasdermin D.

This study aimed to investigate the mechanism of type I interferon (IFN) in aggravating sepsis in bacterial infection, focusing on the roles of Caspase-11 (Casp11) and Gasdermin D (Gsdmd) in this process. Type I interferons, including IFNα and IFNß, were used to treat peritoneal macrophage harvested from wild-type or IFNα/ßR1 knockout (KO) mice, of which the levels of Casp11 and Gsdmd were monitored using real-time polymerase chain reaction (RT-PCR) and Western blot, the exposure to phosphatidylserine was monitored by flow cytometry, and tissue factor (TF) activation was assessed by RT-PCR and TF chromogenic assay. Endotoxemia in wild-type mice led to upregulation of Casp11 and Gsdmd in myeloid cells, which in contrast was attenuated in IFNα/ßR1 KO mice. IFNα or IFNß treatment led to dose-dependent upregulation of Casp11 and Gsdmd in peritoneal macrophages harvested from wild-type mice, but induced negligible changes in IFNα/ßR1 KO mice. Type I IFN promoted phosphatidylserine exposure in peritoneal macrophage from wild-type mice but not IFNα/ßR1 KO mice. Type I IFN induced insignificant changes of TF expression levels in both wild-type mice and IFNα/ßR1 KO mice, but the TF activity was markedly increased in wild-type mice after type I IFN treatment. Our data suggested that the upregulation of Casp11 and Gsdmd in myeloid cells and macrophages induced by endotoxemia was reliant on the expression of IFNα/ßR1. IFNα or IFNß treatment efficiently upregulated Casp11 and Gsdmd, phosphatidylserine exposure, and TF activity of macrophages. Therefore, type I IFN could aggravate sepsis through upregulating Casp11 and Gsdmd.