Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Nat Commun. 2024 Nov 5;15(1):9525. doi: 10.1038/s41467-024-52953-8.
Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood, including protection from the development of febrile symptoms, which is observed in individuals residing in areas with moderate-to-high transmission by early adolescence. Here, we demonstrate that susceptibility to febrile malaria following Plasmodium falciparum infection is associated with the composition of the gut microbiome prior to the malaria season in 10-year-old Malian children, but not in younger children. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children were shown to have a significantly higher parasite burden following Plasmodium infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children. The fecal microbiome of the susceptible children was determined to be enriched for bacteria associated with inflammation, mucin degradation and gut permeability, and to have increased levels of nitric oxide-derived DNA adducts and lower levels of mucus phospholipids compared to the resistant children. Overall, these results indicate that the composition of the gut microbiome is associated with the prospective risk of febrile malaria in Malian children and suggest that modulation of the gut microbiome could decrease malaria morbidity in endemic areas.
疟疾是一个主要的公共卫生问题，但这种疾病发病机制的许多因素还不是很清楚，包括对发热症状发展的保护，这在居住在中高传播地区的个体中从青春期早期就可以观察到。在这里，我们证明，在疟疾流行季节之前，10 岁马里儿童的肠道微生物组组成与感染疟原虫后发生发热性疟疾的易感性有关，但在年龄较小的儿童中则没有。与感染疟原虫的易感性儿童的粪便样本定植的无菌小鼠相比，与抗疟原虫儿童的粪便样本定植的无菌小鼠的寄生虫负荷显著更高。易感性儿童的粪便微生物组被确定为与炎症、粘蛋白降解和肠道通透性相关的细菌富集，并具有更高水平的一氧化氮衍生的 DNA 加合物和更低水平的粘液磷脂，与抗性儿童相比。总的来说，这些结果表明，肠道微生物组的组成与马里儿童发热性疟疾的未来风险有关，并表明调节肠道微生物组可以降低流行地区的疟疾发病率。
