Study on new functions survey of nondigestible oligosaccharide and dietary fiber using accelerated senescence model mouse

本研究旨在探讨长期饲喂难消化低聚糖（FOS）和膳食纤维（GM）饲粮可抑制衰老加速小鼠易感6号和易感8号（SAMP6和SAMP8）发生先天性代谢错误的原因。饲粮的组成改变了肠道菌群，并改变了代谢活性。肠道微生物的产物在数量和质量上都发生了变化，影响了宿主的生存。为了阐明FOS和GM饲喂对肠道微生物群变化与宿主肠道生命活动的相互作用，我们研究了与氧化应激、免疫功能和骨代谢相关的生物标志物的变化。2012年和2013年，分别饲喂对照日粮（CONT）、FOS日粮和GM日粮32周和43周，测定SAMP6 （n=45）和SAMP8 (n=45) 3组（每组n=15）和SAMP8（每组n=15）的生物学指标。饲喂FOS日粮和转基因日粮的SAMP6肠道微生物得到改善，骨代谢变得非常优异。其中，FOS组双歧杆菌数量显著增加，β-葡萄糖苷酶和β-半乳糖苷酶活性降低；GM组梭菌数量显著增加，β-葡萄糖苷酶和β-半乳糖苷酶活性升高。然而，对RANKL和1CTP的影响在FOS组和GM组之间存在差异。结果表明，FOS和GM的作用机制在FOS和GM之间存在差异。分别饲喂FOS和GM日粮，测定SAMP8记忆学习障碍和氧化指标（BAP、d-ROMs、8-OHdG、异戊二醇）。FOS组和GM组小鼠肠道菌群得到改善，脑组织衰老得到延缓。此外，与对照组相比，抗氧化功能增强，炎症因子受到抑制。2013年，以脑功能为重点，在CONT日粮和FOS日粮上分别提高SAMP8，并在CONT日粮上提高SAMR（正常衰老），为期40周，研究记忆和学习障碍、肠道微生物和脑功能（淀粉样蛋白-β、儿茶酚胺、脑组织组织化学、细胞因子、氧化应激标志物等）之间的相互作用。摄入果寡糖可抑制脑内淀粉样蛋白-β的积累，但对儿茶酚胺的浓度没有影响。食用果寡糖可降低炎症细胞因子，增加抗炎细胞因子。氧化应激指标如Bap试验、d-Roms试验、8-OHdG和异戊二酮均因FOS摄入而改善。这些结果表明，长期摄入FOS和GM可以改善肠道微生物，抑制或延缓SAMP8的学习记忆障碍和衰老。因此，肠道菌群对氧化应激和淀粉样蛋白-β沉积的抑制与衰老和脑功能有关。少

The object of the present study was to investigate the cause which the onset of inborn error of metabolism is suppressed, when senescence accelerated mouse-prone 6 and 8 (SAMP6 and SAMP8) were raised on non-digestible oligosaccharide (FOS) and dietary fiber (GM) diets for long period. The composition of diet fed changes intestinal microflora and is transformed the activity of metabolism. As a result, the products of intestinal microbes are changed quantitatively and qualitatively and the existence of host is affected. To clarify the interaction between the change of intestinal microflora and the vital activity of host via intestinal by FOS and GM feeding, the variation of biological markers in concerned with oxidative stress, immune function, and bone metabolism was investigated. In 2012 and 2013, SAMP6 (n=45) with three groups (n=15 each group) and SAMP8 (n=45) with three groups (n=15 each group) were raised on control diet (CONT), FOS diet and GM diet for 32 weeks or 43 weeks, and th … More e biological markers were determined. In SAMP6 fed FOS diet and GM diet, intestinal microbes wereimproved and the bone metabolism became a very excellent. In especially, Bifidobacterium increased markedly and the activity of β-glucronidase and β-galactosidase decreased in FOS group, while in GM group Clostridium increased and the activity of β-glucronidase and β-galactosidase increased. However, the effect for RANKL and 1CTP was different from between FOS group and GM group. These results demonstrate that the function mechanism of FOS and GM are different between FOS and GM. SAMP8 fed FOS diet and GM diet was determined memory and learning disorder and oxidative markers such as BAP test, d-ROMs test, 8-OHdG and isopratan. In FOS group and GM group, intestinal microbes were improved and the senescence of brain was delayed. In addition, anti-oxidative function increased in comparison with that of control group, and inflammatory cytokines were suppressed. In 2013, in focus to brain function, SAMP8 was raised on CONT diet and FOS diet, and SAMR (normal senescence) was raised on CONT diet for 40 weeks to investigate the interaction among the memory and learning disorder, intestinal microbes and brain functions (amyloid-β, catecholamine, brain histochemistry, cytokines, oxidative stress marker s and et al.). The accumulation of amyloid-β in brain was suppressed by FOS ingestion, but the concentration of catecholamine was not changed. Inflammatory cytokineswere decreased by FOS ingestion, and anti-inflammatory cytokines were increased. The oxidative stress markers such as Bap test, d-Roms test, 8-OHdG and isoprastan were improved by FOS ingestion. These results demonstrate that long-term intake of FOS and GM improves intestinal microbes and also suppress or delay the learning and memory disorder and the aging in SAMP8. Thus, the suppression of oxidative stress and deposition of amyloid-β through intestinal microflora is concerned with senescenceand brain function. Less