摘要: | 背景:自閉症類群障礙 (Autism spectrum disorder, ASD) 是一種廣泛存在的神經發育障礙,並且經常合併有腸胃道症狀 (Gastrointestinal symptoms, GIS),盛行率高達55%,更存在腸道菌相失衡的情形。因此調節腸道菌相被視為一種有潛力的替代療法。然而現有文獻回顧文章對於以上方法之效果仍未有一量化結論。因此本研究將使用統合分析方法,探討調節腸道菌相方法對ASD兒童及青少年的腸胃道症狀改善和腸道菌相變化的影響。方法:於五個資料庫中根據 PICOs 關鍵字設定搜尋策略 (P, Children or adolescents with ASD; I, Gut microbial-based intervention; C, Placebo or baseline; O, GIS or gut microbiota),納入人體研究,排除動物研究,蒐集至2024年6月27日國內外研究結果進行統合分析。納入給予ASD兒童益生質、益生菌、共生質及進行糞便微生物移植的人體研究,萃取包含腸胃道症狀、α-diversity、菌門及菌屬豐富度的結果,並以隨機效應模型進行統合分析,結果呈現於森林圖中。結果:本統合分析共納入了18項研究,共包含924名ASD兒童。結果顯示,腸道菌相調整介入後,腸胃道症狀顯著下降 (SMD = -1.3837 [-2.1542; -0.6133]; p = 0.0021);6-GSI分數顯著下降1.86分 [-3.2914; -0.4360] (p = 0.0187);Bifidobacterium豐富度顯著增加 (SMD = 0.6258 [-0.0727; 1.1599]; p = 0.0205)。此外,分組分析結果顯示相較於較短的介入時間 (< 8週),較長的介入時間 (? 8週) 在改善腸胃道症狀方面更有顯著效果;而介入物中之益生菌對於改善腸胃道症狀更為有效。結論:腸道菌相調整方法,特別是益生菌,透過調節腸道菌叢組成,增加Bifidobacterium的豐富度,改善ASD兒童整體的腸胃道症狀,包含便秘、腹瀉、糞便軟硬度、糞便氣味、腹脹及腹痛。 Background: Children with Autism spectrum disorder (ASD) often exhibit gastrointestinal symptoms (GIS), with a high prevalence rate of 55%, and gut dysbiosis. However, current research has not explored this issue in depth, focusing solely on behavioral symptoms. Objectives: This study employed meta-analysis to evaluate the effects of gut microbial-based interventions on GIS and gut microbiota in ASD children. Methods: Five databases were searched for domestic and international research results from inception date to June 27, 2024, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses, with the priori-defined protocol registered at PROSPERO (CRD42023478040). We included human studies that provided ASD children with prebiotics, probiotics, synbiotics or fecal microbiota transplantation (FMT). The effects of gut microbial-based intervention on GIS and gut microbiota in alpha diversity and genera and phylum level were extracted and analyzed using random-effects model in forest plots. Results: A total of 18 randomized clinical trials involving 924 ASD children were included in this study. Meta-analysis results showed that after gut microbial-based interventions, there was a significant improvement in GIS (SMD = -1.3837 [-2.1542; -0.6133]; p = 0.0021). Additionally, there was a significant reduction of 1.86 points in the 6-GSI score (MD = -1.8637 [-3.2914; -0.4360]; p = 0.0187). While there was no significant change in α-diversity or relative abundance at the phylum and genus levels, a significant increase was observed in the abundance of Bifidobacterium (SMD = 0.6258 [-0.0727; 1.1599]; p = 0.0205). Moreover, a longer treatment duration (? 8 weeks) tended to be more effective than a shorter duration (< 8 weeks) in improving GIS, and probiotics showed a significant effect on ameliorating GIS. Conclusion: Gut microbial-based intervention, especially probiotics, can ameliorate the overall GIS in children with ASD by modulating the composition of gut microbiota, particularly by increasing the abundance of Bifidobacterium leading to improvements in symptoms such as constipation, diarrhea, stool consistency, stool smell, flatulence, and abdominal pain. |