Probiotic Administration for Adolescent Depression

益生菌治疗青少年抑郁症

• 批准号: 10646130
• 负责人: Cherry Leung
• 金额: $ 56.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646130
• 关键词: 15 year old; Adherence; Adolescence; Adolescent; Adult; Affect; Age; Bacteria; Beck depression inventory; Biological; Brain; Clinical; Consensus; Data; Depressed mood; Depressive disorder; Development; Diagnosis; Dose; Exhibits; Female; Formulation; Functional Magnetic Resonance Imaging; Future; Gastrointestinal tract structure; Genetic Materials; Hippocampus; Hydrocortisone; Intake; Intervention; Knowledge; Lactobacillus; Left; Literature; Measures; Mediating; Mental Depression; Mental Health; Methods; Neurosecretory Systems; Outcome; Pathway interactions; Patients; Phase; Placebos; Practice Guidelines; Predisposition; Prevalence; Prevention; Probiotics; Public Health; Publishing; Randomized; Randomized, Controlled Trials; Reporting; Research; Rest; Safety; Severities; Testing; Youth; adolescent-onset depression; child depression; clinical diagnosis; clinical practice; clinical remission; depressed patient; depressive symptoms; design; dietary supplements; disability; efficacy trial; gut dysbiosis; gut microbiome; gut microbiota; gut-brain axis; hypothalamic-pituitary-adrenal axis; improved; innovation; insight; male; microbiota; microorganism; physical conditioning; placebo group; prevent; probiotic therapy; recruit; timeline; treatment comparison; treatment group

PROJECT SUMMARY/ABSTRACT. Adolescence is a sensitive developmental period in which prevalence rates of depression sharply increase. Our current first-line treatments are often ineffective in achieving clinical remission in adolescents with depression. Thus, given the poor mental and physical health outcomes associated with adolescent-onset depression, new interventions are urgently needed for the treatment of this debilitating condition. Probiotics, dietary supplements consisting of live beneficial bacteria that can improve dysbiosis of the gut microbiota, are a promising treatment for adolescent depression. While there is no consensus in the scientific literature supporting which probiotic to administer since current probiotic formulations consist of various different bacterial strains and species, research suggests that multi-strain probiotics may be more efficacious than single-strain probiotics in preventing and treating gut dysbiosis. Therefore, the primary objective is to study adolescents diagnosed with a clinical depressive disorder undergoing Visbiome®, a multi-strain probiotic, treatment to determine changes in two biological signatures: (1) the left hippocampus–precuneus (HP) resting-state functional connectivity (RSFC) of the brain and (2) Lactobacillus abundance of the gut microbiome (bacteria and other microorganisms and their genetic materials that reside in the gastrointestinal tract). The central hypothesis is based on the gut-brain axis, where the gut microbiome influences the hippocampus and precuneus, and thus depression. Guided by published literature and strong preliminary data, this hypothesis will be tested by studying changes in the left HP RSFC, gut microbiome, and depressive symptoms in two randomized controlled trials (RCTs). The R61 phase will consist of 77 depressed adolescents randomized to either Visbiome® 450 billion CFU bacteria twice daily group or placebo twice daily group. The R33 phase will consist of 77 depressed adolescents randomized to one of three groups: (1) Visbiome® 450 billion CFU bacteria twice daily, (2) Visbiome® 900 billion CFU bacteria twice daily, or (3) placebo twice daily group. “Go/No-Go Criterion”: To advance from the R61 to R33 phase, the probiotic group vs. placebo group must meet the following effect size threshold for either the left HP RSFC or Lactobacillus: ηp2 ≥ 0.06 (p<0.05). The R33 phase will also collect data to help determine the optimal dose of probiotics for a subsequent larger efficacy trial. The proposed research is innovative because it will inform the design of a future efficacy trial that has the potential to change clinical practice or practice guidelines. The proposed research is significant since it is expected to greatly advance our knowledge and understanding of the underlying mechanism by which probiotics improve depressive symptoms in adolescents, which will ultimately inform the treatment and prevention of adolescent depression.

项目摘要/摘要。青少年是一个敏感的发育时期，抑郁症的患病率急剧增加。我们目前的一线治疗通常无法在抑郁症的青少年中实现临床缓解无效。鉴于与青少年发作抑郁症相关的精神和身体健康状况不佳，迫切需要采取新的干预措施来治疗这种衰弱的状况。益生菌，包括可以改善肠道菌群营养不良的活细菌组成的饮食补充剂，是青少年抑郁症的一种有前途的治疗方法。虽然科学文献中没有共识，但由于当前的益生菌配方由各种不同的细菌菌株和物种组成，因此支持哪种益生菌要施用，但研究表明，多晶型益生菌在预防和治疗肠肠癌中的多晶粒益生菌可能比单义益生菌更有效。因此，主要目标是研究被诊断患有Visbiome®的临床抑郁症的青少年（一种多晶型益生菌），以确定两个生物学特征的变化：（1）左海马 - 普罗果（HP）静息状态功能连接性（RSFC）和其他脑（2）lactobia anctria anctia and（2）lactiaus ractiabia the gut ractiabia the gut gut ractactiation gut gut ractactiation gut ractactia和gut ractactia和gut ractactia和gut c。微生物及其遗传材料位于胃肠道中）。中心假设基于肠道轴，其中肠道微生物组影响海马和前室，从而影响抑郁症。在已发表的文献和强大的初步数据的指导下，该假设将通过研究左HP RSFC，肠道微生物组和抑郁症状的变化来检验，并在两个随机对照试验（RCT）中进行抑郁症状。 R61期将由77个抑郁症青少年组成，每天两次将4,500亿个CFU细菌或安慰剂组成。 R33期将由77个抑郁青少年组成，随机分为三组之一：（1）Visbiome®450亿次CFU细菌每天两次，（2）Visbiome®9000亿CFU细菌每天两次两次，或（3）安慰剂两次组。 “ GO/No-Go标准”：要从R61降低到R33期，益生菌组与安慰剂组必须满足左HP RSFC或乳酸杆菌的以下效果大小阈值：ηp2≥0.06≥0.06（P <0.05）。 R33阶段还将收集数据，以帮助确定随后进行更大效率试验的最佳益生菌剂量。拟议的研究具有创新性，因为它将为未来效率试验的设计提供信息，该试验有可能改变临床实践或实践指南。拟议的研究很重要，因为有望大大提高我们对益生菌改善青少年抑郁症状的潜在机制的知识和理解，这最终将为青少年抑郁症的治疗和预防提供信息。