Butyrate Supplementation at High Concentrations Alters Enteric Bacterial Communities and Reduces Intestinal Inflammation in Mice Infected with Citrobacter rodentium.
Butyrate Supplementation at High Concentrations Alters Enteric Bacterial Communities and Reduces Intestinal Inflammation in Mice Infected with Citrobacter rodentium.
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高浓度下的丁酸酯补充剂会改变肠细菌群落，并减少感染了柠檬酸啮齿动物的小鼠的肠道炎症。
DOI：
10.1128/msphere.00243-17
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发表时间：
2017-07
期刊：
影响因子：
4.8
通讯作者：
Inglis GD
中科院分区：
文献类型：
--
作者：
Jiminez JA;Uwiera TC;Abbott DW;Uwiera RRE;Inglis GD
研究结果提供的证据表明，以剂量依赖性方式给予丁酸盐可以改善感染小鼠的体重增加，增强感染的清除，通过改变细胞因子表达减少炎症，并增强组织修复和粘液分泌。此外，丁酸盐治疗还影响了非炎症和炎症肠道中细菌种群的丰度。值得注意的是，这项研究提供了基础信息，可用于确定益生元和其他功能性食品对肠道细菌产生丁酸的影响及其对肠道健康和宿主健康的影响。丁酸盐是大肠中膳食可发酵物质微生物发酵的短链脂肪酸副产物;它是肠上皮细胞再生的主要能量来源，调节肠道微生物群落，并通过相对不明确的机制促进宿主健康。有限的研究已经检查了丁酸盐的治疗潜力，使用由病原体引起的肠道炎症模型。我们使用啮齿类柠檬酸杆菌激发急性Th 1/Th 17炎症，以确定丁酸盐对宿主-微生物群关系的影响。对小鼠直肠给予140 mM丁酸盐增加了感染啮齿类梭菌的小鼠的丁酸盐粪便浓度，并增加了摄食量和体重增加。在给予140 mM丁酸盐的感染小鼠中，结肠炎症的组织学评分较低。与未给予丁酸盐的小鼠相比，给予丁酸盐的未感染小鼠中IL 10、TGFβ和Muc 2的表达升高。给予丁酸盐的感染小鼠显示病原体清除所必需的基因表达升高（即，IL 17 A和IL 1 β）和参与上皮屏障修复和恢复的基因（即，Relmβ、Tff 3和Myd 88）。丁酸补充到发炎的结肠增加了变形菌和毛螺菌科的丰度，并减少了梭菌科物种的丰度。给予丁酸盐的肠炎小鼠也表现出粘液相关细菌丰度增加。总之，丁酸盐直肠给药增加了摄食量和体重增加，通过增强免疫调节和组织修复机制的表达改善了啮齿类梭菌诱导的细胞损伤，并增加了肠炎小鼠中丁酸盐产生菌的丰度。重要性研究结果提供了证据，证明以剂量依赖性方式给予丁酸盐可以增加感染小鼠的体重增加，增强感染的清除，通过改变细胞因子表达减少炎症，并增强组织修复和粘液分泌。此外，丁酸盐治疗还影响了非炎症和炎症肠道中细菌种群的丰度。值得注意的是，这项研究提供了基础信息，可用于确定益生元和其他功能性食品对肠道细菌产生丁酸的影响及其对肠道健康和宿主健康的影响。
The study findings provide evidence that administration of butyrate in a dose-dependent manner can improve the weight gain of infected mice, enhance clearance of the infection, reduce inflammation through altered cytokine expression, and enhance tissue repair and mucus secretion. Moreover, butyrate treatment also affected the abundance of bacterial populations in both noninflamed and inflamed intestines. Notably, this investigation provides foundational information that can be used to determine the effects of prebiotics and other functional foods on the production of butyrate by enteric bacteria and their impact on intestinal health and host well-being. Butyrate is a short-chain fatty acid by-product of the microbial fermentation of dietary fermentable materials in the large intestine; it is the main energy source for enterocyte regeneration, modulates the enteric microbial community, and contributes to increasing host health via mechanisms that are relatively poorly defined. Limited research has examined the therapeutic potential of butyrate using models of enteric inflammation incited by pathogenic organisms. We used Citrobacter rodentium to incite acute Th1/Th17 inflammation to ascertain the impact of butyrate on the host-microbiota relationship. Rectal administration of 140 mM butyrate to mice increased fecal concentrations of butyrate and increased food consumption and weight gain in mice infected with C. rodentium. Histological scores of colonic inflammation were lower in infected mice administered 140 mM butyrate. Expression of Il10, Tgfβ, and Muc2 was elevated in noninfected mice administered butyrate in comparison to mice not administered butyrate. Infected mice administered butyrate displayed elevated expression of genes necessary for pathogen clearance (i.e., Il17A and Il1β) and of genes involved in epithelial barrier repair and restoration (i.e., Relmβ, Tff3, and Myd88). Butyrate supplemented to inflamed colons increased the abundances of Proteobacteria and Lachnospiraceae and reduced the abundance of Clostridiaceae species. Mice with enteritis that were administered butyrate also exhibited an increased abundance of mucus-associated bacteria. In summary, rectal administration of butyrate increased feed consumption and weight gain, ameliorated C. rodentium-induced cell injury through enhanced expression of immune regulation and tissue repair mechanisms, and increased the abundance of butyrate-producing bacteria in mice with enteritis. IMPORTANCE The study findings provide evidence that administration of butyrate in a dose-dependent manner can increase weight gain in infected mice, enhance clearance of the infection, reduce inflammation through altered cytokine expression, and enhance tissue repair and mucus secretion. Moreover, butyrate treatment also affected the abundance of bacterial populations in both noninflamed and inflamed intestines. Notably, this investigation provides foundational information that can be used to determine the effects of prebiotics and other functional foods on the production of butyrate by enteric bacteria and their impact on intestinal health and host well-being.