Hassib Lucas, Kanashiro Alexandre, Pedrazzi João Francisco Cordeiro, Vercesi Bárbara Ferreira, Higa Sayuri, Arruda Íris, Soares Yago, de Jesus de Souza Adriana, Jordão Alceu Afonso, Guimarães Francisco Silveira, Ferreira Frederico Rogério
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Oswaldo Cruz Foundation, Institute Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Brain Behav Immun Health. 2024 Dec 11;43:100923. doi: 10.1016/j.bbih.2024.100923. eCollection 2025 Feb.
Schizophrenia is a chronic psychiatric disorder characterized by a variety of symptoms broadly categorized into positive, negative, and cognitive domains. Its etiology is multifactorial, involving a complex interplay of genetic, neurobiological, and environmental factors, and its neurobiology is associated with abnormalities in different neurotransmitter systems. Due to this multifactorial etiology and neurobiology, leading to a wide heterogeneity of symptoms and clinical presentations, current antipsychotic treatments face challenges, underscoring the need for novel therapeutic approaches. Recent studies have revealed differences in the gut microbiome of individuals with schizophrenia compared to healthy controls, establishing an intricate link between this disorder and gastrointestinal health, and suggesting that microbiota-targeted interventions could help alleviate clinical symptoms. Therefore, this meta-analysis investigates whether gut microbiota manipulation can ameliorate psychotic outcomes in patients with schizophrenia receiving pharmacological treatment. Nine studies (n = 417 participants) were selected from 81 records, comprising seven randomized controlled trials and two open-label studies, all with a low risk of bias, included in this systematic review and meta-analysis. The overall combined effect size indicated significant symptom improvement following microbiota treatment (Hedges' g = 0.48, 95% CI = 0.09 to 0.88, p = 0.004, I = 62.35%). However, according to Hedges' g criteria, the effect size was small (approaching moderate), and study heterogeneity was moderate based on I criteria. This review also discusses clinical and preclinical studies to elucidate the neural, immune, and metabolic pathways by which microbiota manipulation, particularly with and genera, may exert beneficial effects on schizophrenia symptoms via the gut-brain axis. Finally, we address the main confounding factors identified in our systematic review, highlight key limitations, and offer recommendations to guide future high-quality trials with larger participant cohorts to explore microbiome-based therapies as a primary or adjunctive treatment for schizophrenia.
精神分裂症是一种慢性精神障碍，其特征是有多种症状，大致可分为阳性、阴性和认知领域。其病因是多因素的，涉及遗传、神经生物学和环境因素的复杂相互作用，其神经生物学与不同神经递质系统的异常有关。由于这种多因素病因和神经生物学，导致症状和临床表现具有广泛的异质性，当前的抗精神病药物治疗面临挑战，这突出了对新型治疗方法的需求。最近的研究表明，与健康对照相比，精神分裂症患者的肠道微生物群存在差异，这在这种疾病与胃肠道健康之间建立了复杂的联系，并表明以微生物群为靶点的干预措施可能有助于缓解临床症状。因此，本荟萃分析调查了肠道微生物群操纵是否能改善接受药物治疗的精神分裂症患者的精神病学结局。从81篇记录中筛选出9项研究（n = 417名参与者），包括7项随机对照试验和2项开放标签研究，所有这些研究的偏倚风险都很低，纳入了本系统评价和荟萃分析。总体合并效应量表明，微生物群治疗后症状有显著改善（Hedges' g = 0.48，95% CI = 0.09至0.88，p = 0.004，I² = 62.35%）。然而，根据Hedges' g标准，效应量较小（接近中等），根据I²标准，研究异质性为中等。本综述还讨论了临床和临床前研究，以阐明微生物群操纵，特别是与[具体菌属1]和[具体菌属2]相关的操纵，可能通过肠-脑轴对精神分裂症症状产生有益影响的神经、免疫和代谢途径。最后，我们讨论了在我们的系统评价中确定的主要混杂因素，强调了关键局限性，并提出了建议，以指导未来开展有更大参与者队列的高质量试验，探索基于微生物群的疗法作为精神分裂症的主要或辅助治疗方法。
