National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, United States.
USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, United States.
Front Endocrinol (Lausanne). 2023 Feb 23;14:1125187. doi: 10.3389/fendo.2023.1125187. eCollection 2023.
Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose.
Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity.
The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity.
In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase.
Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo , , and were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month.
Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy.
https://clinicaltrials.gov/, identifier NCT04209075.
Yadav 博士是 Postbiotics Inc 的首席科学官和联合创始人，与这项工作没有利益冲突。所有其他作者均无利益冲突需要披露。
二甲双胍是唯一批准用于青少年 2 型糖尿病（Y-T2DM）的一线口服降糖药物，但常引起胃肠道（GI）副作用，这可能导致治疗依从性和疗效降低。益生菌摄入可能通过改变微生物群落组成和活性来减少二甲双胍的副作用。
本研究旨在确定补充益生菌改善二甲双胍引起的胃肠道症状的可行性和耐受性，并探讨血糖变化和微生物多样性变化。
在一项两阶段的试点临床试验中，我们比较了在每日服用二甲双胍时，每日补充益生菌或安慰剂奶昔，在 1 周的随机双盲交叉设计（第 1 阶段）中，比较了粪便频率和粪便形状（每 1-2 天）和复合下 GI 症状（每周），然后进行为期 1 个月的开放标签扩展（第 2 阶段）。在每个阶段前后收集血浆血糖标志物和粪便样本。
6 名 Y-T2DM（17.2 ± 1.7 岁（均值 ± 标准差），67%为男性，BMI（42 ± 9 kg/m），HbA1c（6.4 ± 0.6%））完成了干预。粪便频率、粪便成分和 GI 症状评分在组间或研究阶段均无差异。未报告严重或严重不良事件，代谢或血糖标志物也无差异。在第 1 阶段的一周内，发现 、 和 是二甲双胍作用的候选生物标志物。β多样性的主坐标分析表明，二甲双胍/益生菌干预与一周和一个月时微生物群签名的明显变化有关。
在短期二甲双胍治疗中给予益生菌纤维补充剂在 Y-T2DM 中耐受良好，并与微生物组成的适度变化相关。这项研究为探索益生菌-二甲双胍-微生物组相互作用作为辅助二甲双胍治疗的基础提供了概念验证。
https://clinicaltrials.gov/，标识符 NCT04209075。
