Hidalgo-Villeda Fanny, Million Matthieu, Defoort Catherine, Vannier Thomas, Svilar Ljubica, Lagier Margaux, Wagner Camille, Arroyo-Portilla Cynthia, Chasson Lionel, Luciani Cécilia, Bossi Vincent, Gorvel Jean-Pierre, Lelouard Hugues, Tomas Julie
Aix Marseille University, CNRS, INSERM, CIML, Turing Centre for Living Systems, Marseille, France.
Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras.
iScience. 2023 May 19;26(6):106910. doi: 10.1016/j.isci.2023.106910. eCollection 2023 Jun 16.
Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer's patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.
重度急性营养不良（SAM）是一种影响全球数百万儿童的多因素疾病。它与肠道生理、微生物群和黏膜免疫的变化有关，这凸显了开展多学科研究以阐明其完整发病机制的必要性。我们建立了一个实验模型，用断奶小鼠喂养高度缺乏营养的饮食，模拟儿童SAM的关键人体测量学和生理学特征。这种饮食会改变肠道微生物群（分节丝状菌减少、与上皮细胞的空间距离）、新陈代谢（丁酸盐减少）以及免疫细胞群体（派尔集合淋巴结中的溶菌性树突状细胞和肠道Th17细胞耗竭）。营养干预可使动物测量学和肠道生理学快速恢复，但肠道微生物群、新陈代谢和免疫系统无法完全恢复。总之，我们提供了一个SAM的临床前模型，并确定了在免疫系统发育过程中进行未来干预以改善SAM整体缺陷的关键靶点。
