Li Min, Monaco Marcia H, Wang Mei, Comstock Sarah S, Kuhlenschmidt Theresa B, Fahey George C, Miller Michael J, Kuhlenschmidt Mark S, Donovan Sharon M
Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, USA.
Department of Pathobiology, University of Illinois, Urbana, IL, USA.
ISME J. 2014 Aug;8(8):1609-20. doi: 10.1038/ismej.2014.10. Epub 2014 Feb 13.
The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.
在仔猪模型中研究了人乳寡糖（HMO）对黏膜免疫、肠道微生物群以及对轮状病毒（RV）感染反应的影响。新生仔猪单独喂食配方奶（FF），或喂食添加4 g l⁻¹ HMO的配方奶（HMO），或喂食9:1短链低聚半乳糖（3.6 g l⁻¹）和长链低聚果糖（0.4 g l⁻¹）的益生元混合物（PRE）（每组n = 19 - 21），持续15天。在第10天，每组中的仔猪（n = 7 - 8）经口感染猪轮状病毒（RV）OSU株，并每天评估粪便稠度。在第15天收集血液、小肠和结肠内容物。评估血清RV特异性抗体浓度、肠道组织形态学、RV非结构蛋白4（NSP4）和细胞因子mRNA表达。测量结肠内容物的pH、干物质（DM）和短链脂肪酸浓度。通过16S rRNA基因v1 - 3区域焦磷酸测序分析升结肠微生物群。与FF仔猪相比，喂食HMO和PRE的组腹泻持续时间更短。感染改变了肠道组织形态学，增加了血清RV特异性抗体反应和肠道RV NSP4表达，并调节了回肠细胞因子表达。HMO增强了回肠中的1型辅助性T细胞（干扰素-γ）和抗炎（白细胞介素-10）细胞因子，而益生元促进了对感染的RV特异性免疫球蛋白M反应。RV感染和HMO补充改变了肠腔内环境和肠道微生物群。HMO提高了结肠内容物的pH并降低了DM，并增加了未分类的毛螺菌科的丰度，该科包含许多产丁酸菌。总之，HMO和益生元并未预防RV感染的发生，但部分通过调节结肠微生物群和对RV感染的免疫反应，缩短了仔猪RV诱导腹泻的持续时间。
