期刊
MUCOSAL IMMUNOLOGY
卷 14, 期 5, 页码 1113-1126出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-021-00418-2
关键词
-
类别
资金
- Bill and Melinda Gates Foundation [OPP1149233, OPP1159806]
- NIH/NIAID T32 training grants [AI141346, AI007319]
- Bill and Melinda Gates Foundation [OPP1149233, OPP1159806] Funding Source: Bill and Melinda Gates Foundation
By studying infant rhesus macaques and their intestinal samples, it was found that growth faltering is associated with a heightened systemic and mucosal pro-inflammatory state, and a shift in the functional and taxonomic composition of gut microbial communities. These studies provide valuable insights into the outcomes of diarrheal diseases and growth faltering.
Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据