Efficacy and gut dysbiosis of gentamicin-intercalated smectite as a new therapeutic agent against Helicobacter pylori in a mouse model

Abstract

BackgroundHelicobacter pylori eradication rate with conventional standard therapy is decreasing owing to antibiotic resistance, necessitating novel antibacterial strategies against H. pylori. We evaluated the efficacy of a gentamicin-intercalated smectite hybrid (S-GM)-based treatment, and analyzed fecal microbiome composition in H. pylori-infected mice. MethodologyTo evaluate anti-H. pylori efficacy, mice were divided into eight groups, and H. pylori eradication was assessed by Campylobacter-like organism (CLO) test and PCR assay of H. pylori in gastric mucosa. One week after H. pylori eradication, proinflammatory cytokine levels and atrophic changes in gastric mucosa were examined. Stool specimens were collected and analyzed for microbiome changes. The S-GM-based triple regimen decreased bacterial burden in vivo, compared with that in untreated mice or mice treated with other regimens. The therapeutic reactions in the CLO test from gastric mucosa were both 90% in standard triple therapy and S-GM therapy group, respectively. Those of H. pylori PCR in mouse gastric mucosa were significantly lower in standard triple therapy and S-GM therapy groups than in non-treatment group. Toxicity test results showed that S-GM therapy reduced IL-8 level and atrophic changes in gastric mucosa. Stool microbiome analysis revealed that compared with mice treated with the standard triple therapy, mice treated with the S-GM therapy showed microbiome diversity and abundant microorganisms at the phylum level. ConclusionOur results suggested that S-GM is a promising and effective therapeutic agent against H. pylori infection. Author summaryThe eradication rate on Helicobacter pylori (H. pylori) showed decreasing trend due to antibiotic resistance, especially clarithromycin. Therefore, we made a smectite hybrid as a drug delivery system using aminoglycosides antibiotic-gentamicin, and applied it to the mouse stomach wall to confirm the localized therapeutic effect, and set the different treatment duration to verify the effect. As a result, it was confirmed that the therapeutic efficacy of gentamicin (GM)-intercalated smectite hybrid (S-GM) was not inferior to the existing standard triple therapy, based on amoxicillin and clarithromycin, and preserved the diversity of gut microbiome composition. Therefore, a S-GM treatment is expected to be a new alternative regimen to H. pylori infection.