Long‐term changes in the gut microbiota after 14‐day bismuth quadruple therapy in penicillin‐allergic children

Abstract Background Penicillin‐allergic children who are infected with Helicobacter pylori constitute a relatively common subgroup. We aimed to study the short‐term and long‐term effects of bismuth quadruple therapy on gut microbiota in penicillin‐allergic children. Methods We prospectively recruited treatment‐naive children with H pylori infection and H pylori‐ negative asymptomatic children as healthy controls. Patients received 14‐day bismuth quadruple therapy consisting of omeprazole, clarithromycin, metronidazole, and bismuth. Fecal samples were collected at weeks 0, 2, 6, and 52. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. Results Twenty‐two subjects (14 gastritis patients, 8 duodenal ulcer patients) and 23 controls participated in this study. At week 2, alpha diversity was reduced in both gastritis ( P < .05) and ulcer (except P = .16 with Chao 1 index) patients compared with baseline. Some changes persisted at week 6, and all were restored at week 52. Beta diversity was significantly altered 2 weeks after treatment in the gastritis and duodenal ulcer groups ( P = .001, P = .002, respectively) and restored at weeks 6 and 52. The mean relative abundance of Bacteroidetes ( P < .001, P = .005, respectively) decreased and that of Proteobacteria increased ( P < .001, P = .03, respectively). All alterations recovered at week 6 and 52. In both the gastritis and ulcer groups at week 2, some beneficial bacteria were decreased including Bacteroides ( P < .001 and P = .003), Faecalibacterium ( P < .001 and P = .02), Phascolarctobacterium ( P = .002 and P = .004), Roseburia ( P < .001 and P = .13), Bifidobacterium ( P = .08 and P = .04), and Blautia ( P < .001 and P = .002). Some detrimental bacteria were increased including Escherichia‐Shigella ( P < .001 and P = .19), Klebsiella ( P < .001, and P = .09), Enterococcus ( P < .001 and P = .007), and Streptococcus ( P = .002 and P = .004). The changes returned to almost the pre‐eradication level 1 year after therapy. Conclusion Bismuth quadruple therapy causes short‐term dysbiosis of the gut microbiota. Most changes recovered 1‐year post‐eradication, indicating the long‐term safety of H pylori therapy.