Division of Pediatric Gastroenterology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States.
Division of Neonatology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States.
Front Immunol. 2023 Jul 21;14:1192936. doi: 10.3389/fimmu.2023.1192936. eCollection 2023.
Chronic undernutrition is a major cause of death for children under five, leaving survivors at risk for adverse long-term consequences. This review focuses on the role of nutrients in normal intestinal development and function, from the intestinal epithelium, to the closely-associated mucosal immune system and intestinal microbiota. We examine what is known about the impacts of undernutrition on intestinal physiology, with focus again on the same systems. We provide a discussion of existing animal models of undernutrition, and review the evidence demonstrating that correcting undernutrition alone does not fully ameliorate effects on intestinal function, the microbiome, or growth. We review efforts to treat undernutrition that incorporate data indicating that improved recovery is possible with interventions focused not only on delivery of sufficient energy, macronutrients, and micronutrients, but also on efforts to correct the abnormal intestinal microbiome that is a consequence of undernutrition. Understanding of the role of the intestinal microbiome in the undernourished state and correction of the phenotype is both complex and a subject that holds great potential to improve recovery. We conclude with critical unanswered questions in the field, including the need for greater mechanistic research, improved models for the impacts of undernourishment, and new interventions that incorporate recent research gains. This review highlights the importance of understanding the mechanistic effects of undernutrition on the intestinal ecosystem to better treat and improve long-term outcomes for survivors.
慢性营养不良是导致五岁以下儿童死亡的主要原因，使幸存者面临不良长期后果的风险。本综述重点关注营养素在正常肠道发育和功能中的作用，从肠上皮细胞到密切相关的黏膜免疫系统和肠道微生物群。我们研究了营养不良对肠道生理学的影响，再次关注了相同的系统。我们提供了对现有营养不良动物模型的讨论，并回顾了证明仅纠正营养不良并不能完全改善对肠道功能、微生物组或生长的影响的证据。我们综述了通过纳入数据来治疗营养不良的努力，这些数据表明，通过不仅关注提供足够的能量、宏量营养素和微量营养素，而且还关注纠正营养不良导致的异常肠道微生物组的干预措施，改善康复是可能的。理解肠道微生物组在营养不良状态中的作用及其表型的纠正既复杂又具有很大的潜力，可以改善康复效果。我们以该领域的关键未解决问题结束，包括对机制研究的需求增加、对营养不良影响的改进模型以及纳入最新研究成果的新干预措施。本综述强调了理解营养不良对肠道生态系统的机制影响的重要性，以便更好地治疗和改善幸存者的长期预后。
