Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response.

中文翻译：

---

自闭症的基因组、环境、微生物组和代谢组 (GEMMA) 研究设计：通过综合多组学系统生物学方法进行自闭症谱系障碍精准治疗和一级预防的生物标志物识别

自闭症谱系障碍 (ASD) 影响大约五分之一的儿童，自 1960 年以来增加了 35 倍。选定的研究表明，最近患病率增加的部分原因可能是意识和认识的提高以及临床实践或服务的变化可用性。然而，这不足以解释这种流行病学现象。研究指出自闭症谱系障碍与肠道微生物群之间可能存在联系，因为许多患有自闭症谱系障碍的儿童都表现出胃肠道问题。目前的大规模自闭症谱系障碍数据集在提供自闭症谱系障碍机制方面的能力有限，因为它们主要是横断面研究，不允许评估早期生命微生物群组成/功能与后来的自闭症谱系障碍诊断之间的透视关联。在这里，我们描述了 GEMMA（自闭症的基因组、环境、微生物组和代谢组），这是一项由欧盟委员会支持的前瞻性研究，该研究从出生起跟踪高危婴儿，以确定自闭症发展的潜在生物标志物预测因素，然后在大型多组学数据集上进行验证。该项目包括人源化小鼠模型（自闭症谱系障碍先证者的粪便转移）和体外结肠模型的临床（观察和介入试验）和临床前研究。这将支持（人类参与者）微生物组范围关联研究的进展，以确定 ASD 进展和严重程度以及潜在治疗反应的潜在机制的预后微生物组特征和代谢途径。