Forty-five percent of deaths among children under 5 years of age are associated with undernutrition. Globally, almost 200 million children exhibit the two major forms of undernutrition—wasting (low weight-for-height) or stunting (low height-for-age), with many affected by both. Undernutrition is not due to food insecurity alone. Growing evidence indicates that perturbed postnatal gut microbiome development contributes to its pathogenesis. This perspective focuses on defining and repairing these defects in gut microbiome development. We describe an approach that involves the analysis of well-phenotyped human cohorts, followed by preclinical studies using gnotobiotic animals colonized with microbiota from these cohorts. Additionally, these models can be used to identify therapeutic targets and candidates that can then be tested clinically. Furthermore, introducing pretreatment microbiota from trial participants into gnotobiotic animals and re-enacting trial conditions allow mechanisms to be dissected. We highlight these recent advances as well as gaps in existing knowledge that present opportunities for future research.

45% 的 5 岁以下儿童死亡与营养不良有关。在全球范围内，近 2 亿儿童表现出两种主要形式的营养不良——消瘦（身高别体重偏低）或发育迟缓（年龄别身高偏低），其中许多儿童都受到这两种情况的影响。营养不良不仅仅是因为粮食不安全。越来越多的证据表明，出生后肠道微生物群发育紊乱有助于其发病机制。这一观点侧重于定义和修复肠道微生物组发育中的这些缺陷。我们描述了一种方法，该方法涉及对表型良好的人类队列进行分析，然后使用被这些队列中的微生物群定殖的无菌动物进行临床前研究。此外，这些模型可用于确定治疗目标和候选者，然后进行临床测试。此外，将试验参与者的预处理微生物群引入无菌动物并重新制定试验条件可以剖析机制。我们强调了这些最新进展以及现有知识中的差距，这些差距为未来的研究提供了机会。