Protocol of a randomized, double-blind, placebo-controlled study of the effect of probiotics on the gut microbiome of patients with gastro-oesophageal reflux disease treated with rabeprazole.

For patients with gastro-oesophageal reflux symptoms, the preferred treatment is proton pump inhibitor (PPI) administration for approximately 8 weeks. However, long-term use of PPIs can cause gut microbiome (GM) disturbances. This study is designed to evaluate the effect of probiotics combined with a PPI on the GM and gastrointestinal symptoms of patients with gastro-oesophageal reflux disease (GERD). This is a randomized, double-blind, placebo-controlled trial. A total of 120 eligible patients with GERD will be randomized into the experimental group or the control group. The treatment includes two phases: the initial treatment period lasts 8 weeks (weeks 1-8), and the maintenance treatment period lasts 4 weeks (weeks 9-12). During the initial treatment period, the experimental group will take rabeprazole and LiHuo probiotics, and the control group will take rabeprazole and a probiotic placebo; during the maintenance treatment period, the experimental group will take LiHuo probiotics, and the control group will take a probiotic placebo. The primary measure is the change in the GM. The secondary measures are the Reflux Disease Questionnaire (RDQ) score, Gastrointestinal Symptom Rating Scale (GSRS) score, faecal metabolome (FM), body mass index, Los Angeles grade of oesophagitis, adverse event (AE) rate and treatment compliance. Each outcome indicator will be assessed at day 0 (before administration), day 28 and/or 56 (during administration), and day 84 (end of administration) to reveal intragroup differences. AEs will be monitored to assess the safety of LiHuo probiotics. This will be the first trial to use the intestinal flora metagene method to analyse the effects of probiotics on patients with GERD receiving long-term PPI treatment. The goal is to provide evidence for the use of probiotics to reduce intestinal flora disorders and other symptoms of gastrointestinal discomfort in patients with GERD who have used PPIs for a long period. Chinese Clinical Trial Registry (ChiCTR) (NO. ChiCTR2000038409). Registered on November 22, 2020, http://www.chictr.org.cn/showproj.aspx?proj=56358 .

Liu W ，Xie Y ，Li Y ，Zheng L ，Xiao Q ，Zhou X ，Li Q ，Yang N ，Zuo K ，Xu T ，Lu NH ，Zhang H ... -  《BMC GASTROENTEROLOGY》

Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

Ha NY ，Kim JW ，Kim J 《BMC Complementary Medicine and Therapies》

The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.

Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n = 15) or placebo (n = 15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. Short term PPI treatment increased the microbial abundance of Streptococcaceae (p = 0.004), Leuconostacaceae (p = 0.001), and Pasteurellaceae (p = 0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p = 0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p < 0.05) along with other species present in the multi-strain probiotic. Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS. NCT03327051.

Singh G ，Haileselassie Y ，Briscoe L ，Bai L ，Patel A ，Sanjines E ，Hendler S ，Singh PK ，Garud NR ，Limketkai BN ，Habtezion A ... -  《-》

Double-blind comparison [correction of Double-blind, placebo-controlled comparison] of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. The European Rabeprazole Study Group.

Dekkers CP ，Beker JA ，Thjodleifsson B ，Gabryelewicz A ，Bell NE ，Humphries TJ ... -  《-》

Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors : Usual dose proton pump inhibitors plus hangeshashinto versus double-dose proton pump inhibitors: randomized, multicenter open label exploratory study.

Takeuchi T ，Hongo H ，Kimura T ，Kojima Y ，Harada S ，Ota K ，Takeuchi N ，Noguchi T ，Inoue T ，Murano M ，Higuchi K ... -  《-》