Suckling Piglets; Fructooligosaccharides

Emerging knowledge shows the importance of early life events in programming the intestinal mucosal immune system and development of the intestinal barrier function. These processes depend heavily on close interactions between gut microbiota and host cells in the intestinal mucosa. In turn, development of the intestinal microbiota is largely dependent on available nutrients and substrates required for the specific microbial community structures to expand. It is currently not known what the specificities are of intestinal microbial community structures in relation to the programming of the intestinal mucosal immune system and development of the intestinal barrier function. The objective of the present study was to investigate the effect of a nutritional intervention on intestinal development of suckling piglets by daily oral administration of fructooligosaccharides (FOS) over a period of 12 days. At the microbiota community level a clear “bifidogenic” effect of the FOS administration was observed in colon digesta at day 14. The former, however, did not translate into significant changes of local gene expression in the colonic mucosa. In the jejunum, significant changes were observed for microbiota composition at day 14, and microbiota diversity at day 25. In addition, significant differentially expressed gene sets in mucosal tissues of jejunum were identified at both days 14 and 25 of age. At the age of 14 days, lower activity of cell cycle-related processes and a higher activity of extracellular matrix processes were observed in jejunal scrapings of piglets supplemented with FOS compared to control piglets. At day 25, lower activity of immune-related processes in jejunal tissue were seen in piglets supplemented with FOS. Histological parameters, villi height and crypt depth, were significantly different at day 25 between the experimental and control group, where piglets supplemented with FOS had higher villi and deeper crypts. We conclude that oral FOS administration during the suckling period of piglets has significant bifidogenic effects on the microbiota in the colon and on gene expression in jejunal mucosa scrapings. We hypothesize that FOS supplementation of suckling piglets results in a higher butyrate production in the colon due to the increase in bifidobacteria and lactobacilli in the hindgut. We further speculate that a higher butyrate production in colonic digesta relates to changes in gene expression in the jejunum by thus far unknown mechanisms. At day 2, 8 control piglets were sacrificed to obtain the jejunum scrapings. Whereas at days 14 and 25, 16 piglets were sacrificed (8 controls and 8 piglets that received FOS) to obtain the jejunum scrapings. At day 14, we also extracted colon tissue from 8 controls and 8 piglets that received FOS. After quality control in total 51 samples were left (37 jejunum and 14 colon samples).

越来越多的研究证据表明，生命早期事件在肠道黏膜免疫系统的程序化发育以及肠道屏障功能构建过程中发挥关键作用。上述过程高度依赖肠道菌群与肠黏膜宿主细胞之间的紧密互作；反之，肠道菌群的发育在很大程度上依赖于可利用的营养物质与底物，以支撑特定微生物群落结构的增殖扩张。目前，学界仍未明确与肠道黏膜免疫系统程序化发育及肠道屏障功能构建相关的肠道微生物群落结构特异性特征。本研究旨在通过为期12天的每日口服低聚果糖（fructooligosaccharides, FOS）干预，探究营养干预对哺乳仔猪肠道发育的影响。在微生物群落层面，给药后第14天的结肠内容物中可观察到FOS干预产生的明确“双歧杆菌增殖效应”（bifidogenic）；然而，该菌群层面的变化并未转化为结肠黏膜局部基因表达的显著改变。在空肠组织中，给药后第14天的微生物群落组成以及第25天的微生物多样性均出现显著变化。此外，在仔猪日龄14天与25天时，空肠黏膜组织中均检测到显著差异表达的基因集。日龄14天时，与对照组仔猪相比，FOS干预组仔猪的空肠刮取物中，细胞周期相关通路的活性更低，而细胞外基质相关通路的活性更高。至日龄25天时，FOS干预组仔猪的空肠组织中免疫相关通路的活性显著降低。组织学参数方面，两组仔猪在日龄25天时的绒毛高度与隐窝深度存在显著差异：FOS干预组仔猪的小肠绒毛更高、隐窝更深。综上，本研究表明，在仔猪哺乳期间口服FOS干预，可对结肠菌群产生显著的双歧杆菌增殖效应，并可改变空肠黏膜刮取物的基因表达谱。本研究推测，哺乳仔猪补充FOS可通过增加后肠内的双歧杆菌与乳杆菌丰度，进而提升结肠内丁酸的生成水平。本研究进一步推测，结肠内容物中丁酸生成水平的提升与空肠基因表达的改变存在关联，但其具体调控机制目前尚不明确。实验分组中，日龄2天时处死8只对照组仔猪以获取空肠刮取物；而在日龄14天与25天时，各处死16只仔猪（8只对照组、8只FOS干预组）以获取空肠刮取物。在日龄14天时，本研究同时从8只对照组与8只FOS干预组仔猪中提取结肠组织。经质量控制后，最终共保留51份有效样本（其中空肠样本37份、结肠样本14份）。