Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice.
Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice.
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宿主对益生菌的反应由轮状病毒感染的新生小鼠的营养状况决定。
DOI：
10.1097/mpg.0b013e31824d2548
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发表时间：
2012-09
影响因子：
2.9
通讯作者：
Versalovic J
中科院分区：
文献类型：
--
作者：
Preidis GA;Saulnier DM;Blutt SE;Mistretta TA;Riehle KP;Major AM;Venable SF;Barrish JP;Finegold MJ;Petrosino JF;Guerrant RL;Conner ME;Versalovic J
有益微生物和益生菌是预防和治疗儿童肠道和消化道疾病的有前途的药物;然而，对其体内作用机制知之甚少。我们使用轮状病毒腹泻的新生小鼠模型来深入了解益生菌如何改善急性胃肠炎。轮状病毒感染的小鼠用2株人源罗伊氏乳杆菌中的1株进行治疗。我们通过16 S宏基因组测序评估了肠道微生物组组成，通过5-溴-2 ′-脱氧尿苷评估了肠细胞迁移和增殖，并通过肠道外植体培养物的多重分析评估了抗体和细胞因子浓度。益生菌减少腹泻持续时间，改善肠道组织病理学，并增强肠道微生物组丰富性和系统发育多样性。益生菌减少腹泻的幅度是菌株特异性的，并受营养状况的影响。罗伊氏乳杆菌DSM 17938分别使体重不足、正常体重和超重幼鼠的腹泻持续时间减少0、1和2天。腹泻持续时间的减少幅度与肠上皮细胞增殖和迁移的增加相关。菌株ATCC PTA 6475在所有小鼠中将腹泻持续时间减少1天，而不增加肠上皮细胞增殖。两种益生菌菌株都降低了所有动物中促炎细胞因子的浓度，包括巨噬细胞炎性蛋白-1 α和白细胞介素-1 β，并增加了除体重不足动物外的所有动物中的轮状病毒特异性抗体。体重也影响宿主对轮状病毒的反应，包括腹泻持续时间、肠上皮细胞周转和抗体产生。这些数据表明，益生菌增强肠上皮细胞增殖，绒毛再生，和病毒特异性抗体可能有助于腹泻的解决，营养状况影响宿主对有益微生物和病原体的反应。
Beneficial microbes and probiotics are promising agents for the prevention and treatment of enteric and diarrheal diseases in children; however, little is known about their in vivo mechanisms of action. We used a neonatal mouse model of rotavirus diarrhea to gain insight into how probiotics ameliorate acute gastroenteritis. Rotavirus-infected mice were treated with 1 of 2 strains of human-derived Lactobacillus reuteri. We assessed intestinal microbiome composition with 16S metagenomic sequencing, enterocyte migration and proliferation with 5-bromo-2′-deoxyuridine, and antibody and cytokine concentrations with multiplex analyses of intestinal explant cultures. Probiotics reduced diarrhea duration, improved intestinal histopathology, and enhanced intestinal microbiome richness and phylogenetic diversity. The magnitude of reduction of diarrhea by probiotics was strain specific and influenced by nutritional status. L reuteri DSM 17938 reduced diarrhea duration by 0, 1, and 2 days in underweight, normal weight, and overweight pups, respectively. The magnitude of reduction of diarrhea duration correlated with increased enterocyte proliferation and migration. Strain ATCC PTA 6475 reduced diarrhea duration by 1 day in all of the mice without increasing enterocyte proliferation. Both probiotic strains decreased concentrations of proinflammatory cytokines, including macrophage inflammatory protein-1α and interleukin-1β, in all of the animals, and increased rotavirus-specific antibodies in all but the underweight animals. Body weight also influenced the host response to rotavirus, in terms of diarrhea duration, enterocyte turnover, and antibody production. These data suggest that probiotic enhancement of enterocyte proliferation, villus repopulation, and virus-specific antibodies may contribute to diarrhea resolution, and that nutritional status influences the host response to both beneficial microbes and pathogens.