Mechanisms of Probiotics and Antibiotic-Associated Diarrhea
关键词
抽象
描述
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, the efficacy of many probiotic products used for AAD is not supported by rigorous independent research, and non-evidence-based clinical usage is common. Data from several studies are consistent with the notion that antibiotic-induced disruption of commensal bacteria in the colon results in a significant reduction of short chain fatty acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting in AAD. The probiotic strain being studied, Bifidobacterium animalis subsp. lactis BB-12 (BB-12), has been shown to ameliorate a variety of gastrointestinal disease states and is known to produce acetate at concentrations up to 50 mM in vitro. Thus, the investigators hypothesize that administration of BB-12 at the same time as antibiotic consumption will protect against the development of AAD through its ability to generate acetate directly, and also increase other SCFAs through cross-feeding of certain bacteria in the Firmicutes phylum such Clostridium, Eubacterium and Roseburia, which use acetate to produce butyrate.
The primary aim is to determine the ability of BB-12 to impact antibiotic-induced reduction in SCFA as reflected by the levels of acetate, the most abundant primary colonic SCFA, and assess temporal intervals of probiotic administration. The primary hypothesis is that antibiotics will result in a reduction in fecal SCFA, but BB-12 supplementation will protect against antibiotic-induced SCFA reduction and/or be associated with a more rapid return to baseline SCFA levels as compared to controls. Antibiotics also result in a decrease in total microbial counts and diversity in the gut microbiota, disrupting the homeostasis of the gut ecosystem and allowing colonization by pathogens. We hypothesize that concurrent administration of the probiotic and antibiotic is not necessary for the probiotic impact on SCFA.
The secondary aim will be to determine the ability of BB-12 to impact antibiotic-induced disruption of the gut microbiota with 16S ribosomal ribonucleic acid (rRNA) profiling, and assess temporal intervals of probiotic administration. The secondary hypothesis is that antibiotics will result in a decrease in the overall number and diversity of bacterial species present in the fecal microbiota, and further BB-12 supplementation will protect against antibiotic-induced shifts in the microbiota and/or will be associated with a more rapid return to a baseline microbiota composition as compared to controls. We hypothesize that concurrent administration of the probiotic and antibiotic is not necessary for the probiotic effect on the composition of the gut microbiota.
The tertiary aim is to longitudinally characterize the gut microbiota with high-throughput metatranscriptomics in order to generate complementary information on the impact of antibiotics plus and minus BB-12 on overall microbiome function. We hypothesize that acetate produced by BB-12 in situ will cross-feed butyrate producers in the Firmicutes phylum resulting in an up-regulation of butyrate biosynthetic pathways.
The long-term goal is to determine the impact of BB-12 on a variety of gastrointestinal disease states and ages, through high-level independent research. This mechanism elucidation is important for directing future translational and effectiveness research.
日期
最后验证: | 05/31/2020 |
首次提交: | 05/31/2020 |
提交的预估入学人数: | 05/31/2020 |
首次发布: | 06/03/2020 |
上次提交的更新: | 05/31/2020 |
最近更新发布: | 06/03/2020 |
实际学习开始日期: | 11/30/2020 |
预计主要完成日期: | 07/31/2022 |
预计完成日期: | 07/31/2023 |
状况或疾病
干预/治疗
Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
Biological: BB-12
Other: Control
相
手臂组
臂 | 干预/治疗 |
---|---|
Placebo Comparator: Concurrent control yogurt and amoxicillin-clavulanate Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time | |
Placebo Comparator: Control yogurt taken 4 hours after amoxicillin-clavulanate Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet | |
Active Comparator: Concurrent BB-12 yogurt and amoxicillin-clavulanate Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time | |
Active Comparator: BB-12 yogurt taken 4 hours after amoxicillin-clavulanate Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet | |
Other: Amoxicillin-clavulanate Amoxicillin-clavulanate 875 mg-125 mg oral tablet |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: - Has the ability to read, speak, and write in English - Has a refrigerator (for proper storage of the study yogurt) - Has reliable telephone access - Is between ages of 18-65 years - Agree to refrain from eating yogurts, yogurt drinks, and other foods specified in the provided list - Agree to collect stool samples and participate in follow-up calls as specified Exclusion Criteria: - Diabetes or asthma that requires medication - Allergy to strawberry - Active diarrhea (three or more loose stools per day for two consecutive days) - Any gastrointestinal (or digestive tract) medications, i.e. medicines for irritable bowel syndrome, gastroesophageal (acid) reflux disease, inflammatory bowel disease, etc. - History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic - History of gastrointestinal surgery or disease - Lactose intolerance that prevents participant from eating yogurt - Allergy to milk-protein - Allergy to any component of the product or the yogurt vehicle - Allergy to penicillin or cephalosporin class antibiotics - Allergy to any of the following medications: a) Penicillin; b) Erythromycin; c) Tetracycline; d) Trimethoprim; e) Ciprofloxacin - Women who are breastfeeding, pregnant, or planning to become pregnant during the study |
结果
主要结果指标
1. Change from baseline levels of fecal short-chain fatty acid at day 7 [day 7]
2. Change from baseline levels of fecal short-chain fatty acid at day 14 [day 14]
3. Change from baseline levels of fecal short-chain fatty acid at day 21 [day 21]
4. Change from baseline levels of fecal short-chain fatty acid at day 30 [day 30]
次要成果指标
1. Change in baseline diversity of bacterial species in fecal microbiota as assessed by Shannon index [day 7, 14, 21, 30]
2. Change in baseline diversity of bacterial species in fecal microbiota as assessed by Bray-Curtis dissimilarity [day 7, 14, 21, 30]
3. Change in baseline diversity of bacterial species in fecal microbiota as assessed by Chao1 metric [day 7, 14, 21, 30]
4. Change in baseline number of bacterial species in fecal microbiota [day 7, 14, 21, 30]