AUTHOR=Zhao Yuchong , Yang Yilei , Aruna  , Xiao Jun , Song Jun , Huang Tizheng , Li Shuyu , Kou Jiguang , Huang Lu , Ji Dexiong , Xiong Si , Peng Wang , Xu Sanping , Cheng Bin 

TITLE=Saccharomyces boulardii Combined With Quadruple Therapy for Helicobacter pylori Eradication Decreased the Duration and Severity of Diarrhea: A Multi-Center Prospective Randomized Controlled Trial

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.776955

DOI=10.3389/fmed.2021.776955

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Whether probiotics helped the <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>) eradication was still highly controversial. The non-bacterial <italic>Saccharomyces boulardii</italic> (<italic>S. boulardii</italic>) has demonstrated its efficacy in the treatment of antibiotic-associated and infectious diarrhea. We aimed to evaluate the effects of <italic>S. boulardii</italic> combined with quadruple therapy for <italic>H. pylori</italic> eradication and associated side effects.</p><p><bold>Methods:</bold> Three hundred and sixty <italic>H. pylori-</italic>infected patients were recruited in this multicenter, randomized controlled trial. The patients who underwent <italic>H. pylori</italic> eradication treatment were randomized in a ratio of 1:1 into two separate groups that received standard quadruple therapy (Group A) and quadruple therapy plus <italic>S. boulardii</italic> sachets (Group B) for 14 days. The everyday medication and side-effect records were collected for compliance and adverse effect analysis. All patients accepted <sup>13</sup>C/<sup>14</sup>C-urea breath tests 4 weeks after the therapy completion.</p><p><bold>Results:</bold><italic>Saccharomyces boulardii</italic> and quadruple therapy-combined intervention significantly reduced the incidences of overall side effects (27.8 vs. 38.5%, <italic>p</italic> = 0.034) and diarrhea (11.2 vs. 21.2%, <italic>p</italic> = 0.012) in Group B compared with quadruple therapy alone in Group A, especially reduced the diarrhea duration (5.0 days vs. 7.7 days, <italic>p</italic> = 0.032) and incidence of severe diarrhea (4.7 vs. 10.1%, <italic>p</italic> = 0.040). Intention-to-treat (ITT) analysis and per-protocol (PP) analysis both indicated no statistical differences of eradication rate between Groups A and B (ITT: 82.7 vs. 85.8%, <italic>p</italic> = 0.426; PP: 89.7 vs. 94.2%, <italic>p</italic> = 0.146). The joint use of <italic>S. boulardii</italic> and quadruple therapy markedly improved the overall pre-eradication alimentary symptoms (hazard ratio (HR): 2.507, 95% CI: 1.449–4.338) recovery.</p><p><bold>Conclusion:</bold><italic>Saccharomyces boulardii</italic> ameliorated <italic>H. pylori</italic> eradication<italic>-</italic>induced antibiotic-associated side effects especially reduced the incidence of severe diarrhea and the duration of diarrhea. However, there was no significant effect of <italic>S. boulardii</italic> on the rate of <italic>H. pylori</italic> eradication.</p><p><bold>Trial Registration:</bold> The protocol had retrospectively registered at <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrails.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrails.gov</ext-link>, Unique identifier: NCT03688828, date of registration: September 27, 2018; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/show/NCT03688828" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/show/NCT03688828</ext-link></p>