Abstract：
BACKGROUND: Dietary supplements can modulate the gut microbial ecosystem and affect the immune system. This has potential implications for autoimmune diseases, including multiple sclerosis (MS). Prior studies explored tolerability, symptomatic improvement, and immunologic effects of probiotics in people with MS (pwMS), but no study has examined prebiotics in this population or compared prebiotics with probiotics.
METHODS: This is a randomized, open-label trial of participants with relapsing-remitting MS on B-cell depletion therapy from two MS centers. 22 participants enrolled in the original cross-over study in which probiotic (Visbiome, containing Lactobacillus, Bifidobacterium and Streptococcus species) or prebiotic (Prebiotin, containing oligofructose enriched inulin) supplementation for 6 weeks was randomized, each followed by a washout period. Due to pandemic-related interruptions and expiration of the study supply of probiotics, another 15 participants enrolled in a single-arm study to receive prebiotic supplementation for 6 weeks followed by a washout period. We assessed supplement tolerability and patient-reported outcomes (PRO) relevant to MS (disability, fatigue, mood, and bowel symptoms) before and after each supplement administration period and each washout period. We bio-archived plasma, serum, peripheral blood mononuclear cells and stool samples at each timepoint for future multi-omic assessment.
RESULTS: Prebiotics and probiotics had comparable adherence rates and both supplements were well tolerated in pwMS. Participants on either supplement reported minor adverse events, most of which were mild and self-limited. There was a subjective preference for prebiotics over probiotics. Comparing supplement-associated changes in PRO scores from baseline to 6 weeks post-supplementation, there were significant difference between prebiotics and probiotics for the change in patient-reported global symptom burden (MSRS-R Total) and bowel control (BWCS), but only probiotics statistically improved bowel control from baseline to post-supplementation.
CONCLUSIONS: Supplementation with either prebiotics or probiotics is reasonably well-tolerated and safe. Probiotics improved bowel control, but did not improve other PROs in a 6-week time frame. These data regarding feasibility, tolerability, adherence, and adverse events of supplements will inform future clinical trial designs to definitively compare the efficacy and safety of prebiotics and probiotics. The biological data that will be generated from this study in the future will provide mechanistic insights into the effects of these dietary supplements on MS pathophysiology.
METHODS: This is a randomized, open-label trial of participants with relapsing-remitting MS on B-cell depletion therapy from two MS centers. 22 participants enrolled in the original cross-over study in which probiotic (Visbiome, containing Lactobacillus, Bifidobacterium and Streptococcus species) or prebiotic (Prebiotin, containing oligofructose enriched inulin) supplementation for 6 weeks was randomized, each followed by a washout period. Due to pandemic-related interruptions and expiration of the study supply of probiotics, another 15 participants enrolled in a single-arm study to receive prebiotic supplementation for 6 weeks followed by a washout period. We assessed supplement tolerability and patient-reported outcomes (PRO) relevant to MS (disability, fatigue, mood, and bowel symptoms) before and after each supplement administration period and each washout period. We bio-archived plasma, serum, peripheral blood mononuclear cells and stool samples at each timepoint for future multi-omic assessment.
RESULTS: Prebiotics and probiotics had comparable adherence rates and both supplements were well tolerated in pwMS. Participants on either supplement reported minor adverse events, most of which were mild and self-limited. There was a subjective preference for prebiotics over probiotics. Comparing supplement-associated changes in PRO scores from baseline to 6 weeks post-supplementation, there were significant difference between prebiotics and probiotics for the change in patient-reported global symptom burden (MSRS-R Total) and bowel control (BWCS), but only probiotics statistically improved bowel control from baseline to post-supplementation.
CONCLUSIONS: Supplementation with either prebiotics or probiotics is reasonably well-tolerated and safe. Probiotics improved bowel control, but did not improve other PROs in a 6-week time frame. These data regarding feasibility, tolerability, adherence, and adverse events of supplements will inform future clinical trial designs to definitively compare the efficacy and safety of prebiotics and probiotics. The biological data that will be generated from this study in the future will provide mechanistic insights into the effects of these dietary supplements on MS pathophysiology.
摘要：
背景：膳食补充剂可以调节肠道微生物生态系统并影响免疫系统。这对自身免疫性疾病有潜在的影响，包括多发性硬化症（MS）。先前的研究探索了耐受性，症状改善，益生菌对MS患者的免疫作用（pwMS），但没有研究对该人群中的益生元进行过研究，也没有将益生元与益生菌进行比较。
方法：这是一个随机的，两个MS中心的B细胞耗竭治疗复发缓解型MS参与者的开放标签试验.22名参与者参加了最初的交叉研究，其中益生菌(Visbiome，含有乳酸菌，双歧杆菌和链球菌）或益生元（前生物素，含有富含寡糖的菊粉）补充6周的随机分组，每个都跟着一个冲洗期。由于大流行相关的中断和益生菌的研究供应到期，另外15名参与者参加了一项单组研究,接受6周的益生元补充剂,然后进行一个清除期.我们评估了补充耐受性和患者报告的结果（PRO）与MS（残疾，疲劳,心情,和肠道症状）在每个补充给药期和每个清除期之前和之后。我们生物存档的等离子体，血清,每个时间点的外周血单个核细胞和粪便样本，用于未来的多组评估。
结果：益生元和益生菌具有相当的依从率，并且两种补充剂在pwMS中的耐受性良好。两种补充剂的参与者都报告了轻微的不良事件，其中大多数是温和和自我限制的。与其说是益生菌，不如说是一种主观偏好。比较从基线到补充后6周的PRO评分的补充相关变化，在患者报告的总体症状负担（MSRS-RTotal）和肠道控制（BWCS）的变化方面，益生元和益生菌之间存在显着差异，但只有益生菌在统计学上改善了从基线到补充后的肠道控制.
结论：补充益生元或益生菌是相当好的耐受性和安全性。益生菌改善肠道控制，但在6周的时间范围内没有改善其他专业人员。这些关于可行性的数据，耐受性,坚持,补充剂的不良事件将为未来的临床试验设计提供信息，以明确比较益生元和益生菌的疗效和安全性。未来将从这项研究中产生的生物学数据将为这些膳食补充剂对MS病理生理学的影响提供机制见解。
方法：这是一个随机的，两个MS中心的B细胞耗竭治疗复发缓解型MS参与者的开放标签试验.22名参与者参加了最初的交叉研究，其中益生菌(Visbiome，含有乳酸菌，双歧杆菌和链球菌）或益生元（前生物素，含有富含寡糖的菊粉）补充6周的随机分组，每个都跟着一个冲洗期。由于大流行相关的中断和益生菌的研究供应到期，另外15名参与者参加了一项单组研究,接受6周的益生元补充剂,然后进行一个清除期.我们评估了补充耐受性和患者报告的结果（PRO）与MS（残疾，疲劳,心情,和肠道症状）在每个补充给药期和每个清除期之前和之后。我们生物存档的等离子体，血清,每个时间点的外周血单个核细胞和粪便样本，用于未来的多组评估。
结果：益生元和益生菌具有相当的依从率，并且两种补充剂在pwMS中的耐受性良好。两种补充剂的参与者都报告了轻微的不良事件，其中大多数是温和和自我限制的。与其说是益生菌，不如说是一种主观偏好。比较从基线到补充后6周的PRO评分的补充相关变化，在患者报告的总体症状负担（MSRS-RTotal）和肠道控制（BWCS）的变化方面，益生元和益生菌之间存在显着差异，但只有益生菌在统计学上改善了从基线到补充后的肠道控制.
结论：补充益生元或益生菌是相当好的耐受性和安全性。益生菌改善肠道控制，但在6周的时间范围内没有改善其他专业人员。这些关于可行性的数据，耐受性,坚持,补充剂的不良事件将为未来的临床试验设计提供信息，以明确比较益生元和益生菌的疗效和安全性。未来将从这项研究中产生的生物学数据将为这些膳食补充剂对MS病理生理学的影响提供机制见解。
