肠道粘膜免疫功能缺陷与肠道菌群失调导致生长缓慢
  • 以恒河猴幼仔为研究对象,分析比较了健康组(HG)、有或无急性腹泻病史的生长缓慢组(GF)、慢性活动性腹泻生长缓慢组(GF-DX)的肠道免疫功能和菌群组成;
  • 两个GF组结肠粘膜炎性水平均较高,但经LPL刺激,促炎反应较HG组减弱,提示有免疫耗竭情况;
  • 两个GF组不同肠道节段的菌群组成相比HG发生明显改变,功能菌群组成变化,且异位,表现为链球菌和普氏菌在小肠和大肠之间的迁移,表明肠道微生物群落区化情况消失。
主编推荐语
Zhonghua
在全球范围内,腹泻仍然是导致幼儿死亡的重要因素。腹泻不仅仅可以导致死亡,而且腹泻引起的肠道功能的改变会对儿童发育造成长远的影响,特别是导致生长缓慢甚至停滞。但是,目前对于腹泻导致肠道损伤、功能的改变、菌群的改变以及致病菌的情况与生长缓慢之间的研究较少。近期一篇发表在Mucosal Immunology的研究工作,以恒河猴幼仔为模式动物,研究了有急性腹泻病史或者活动性慢性腹泻且生长停滞幼仔中粘膜免疫系统和整个肠道微生物群落的变化,结果显示腹泻对于肠道免疫和菌群的改变,在结肠中表现更加明显,具体包括有肠道炎症水平较高,应激能力下降,肠道菌群组成、异位以及菌群区化消失。这些结果提示结肠生态的改变对于生长缓慢具有更显著的影响。
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Mucosal Immunology [IF:7.313]

Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen

无论存在慢性腹泻与否,生长缓慢都与肠腔黏膜免疫功能障碍及微生物失调有关

10.1038/s41385-021-00418-2

06-22, Article

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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.

First Authors:
Nicholas S Rhoades

Correspondence Authors:
Ilhem Messaoudi

All Authors:
Nicholas S Rhoades,Sara M Hendrickson,Kamm Prongay,Andrew Haertel,Leanne Gill,Robert A Edwards,Laura Garzel,Mark K Slifka,Ilhem Messaoudi

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