Exploration of the Interaction Between Bismuth-Containing Quadruple Anti-H. pylori Therapy and the Gut Microbiota

Helicobacter pylori (H. pylori) eradication with bismuth-containing quadruple therapy (BQT) is effective but often accompanied by adverse gastrointestinal reactions and gut microbiota disturbances, while the impact of probiotic supplementation and the predictive value of the gut microbiota remain incompletely understood. In this single-center prospective randomized controlled trial, 109 H. pylori-positive patients were assigned to receive a 14-day BQT alone treatment or BQT combined with compound Lactobacillus acidophilus (LBQT). Fecal samples were collected before treatment, at the end of therapy, and four weeks after completion for 16S rDNA amplicon sequencing to assess microbiota dynamics. Although the addition of compound L. acidophilus did not significantly alter eradication rates, it markedly reduced the incidence of gastrointestinal adverse reactions, accelerated the recovery of gut microbial diversity and abundance, and delayed the overgrowth of potentially pathogenic bacteria, as well as increased short-chain fatty acid-producing bacteria. We further predicted the success of H. pylori eradication using ROC curves, and found that the combined baseline fecal microbiota markers (o_Lactobacillales, o_Enterobacterales, and f_Enterobacteriaceae) achieved an AUC of 0.849 at the start of treatment; at 4 weeks after eradication, the AUC of the microbiota combined with o_Peptostreptococcales, c_Bacilli, o_Lactobacillales, and g_Streptococcus predicted successful eradication up to 0.776. These findings indicate that compound L. acidophilus supplementation alleviates the side effects of BQT and promotes the restoration of gut microbiota homeostasis, and that gut microbiota signatures may serve as noninvasive predictors of treatment tolerance and therapeutic outcome.