Complementary intestinal mucosa and microbiota responses to caloric restriction.

Complementary intestinal mucosa and microbiota responses to caloric restriction.
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DOI:
10.1038/s41598-018-29815-7
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发表时间:
2018-07-27
期刊:
影响因子:
4.6
通讯作者:
Wahli W
Wahli W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Duszka K;Ellero-Simatos S;Ow GS;Defernez M;Paramalingam E;Tett A;Ying S;König J;Narbad A;Kuznetsov VA;Guillou H;Wahli W

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肠道是营养吸收以及微生物群与其宿主之间相互作用的关键。因此,肠道对热量限制(CR)的反应被认为比任何其他器官都更复杂。让小鼠在 14 天内接受 25% CR 诱导十二指肠粘膜细胞基因表达的极化,其特征分别是代谢和免疫/炎症途径的上调和下调。 HNF、PPAR、STAT 和 IRF 转录因子家族,特别是 Pparα 和 Isgf3 基因,被认为是这些过程中潜在的关键参与者。 CR 对肠粘膜代谢基因的影响是通过抑制 mTOR 通路来模拟的。此外,CR 小鼠的多种十二指肠和粪便代谢物发生了改变。这些变化取决于微生物群,其大小与微生物密度相对应。使用肠道细菌耗尽和 CR 特异性微生物群转移的小鼠进行的进一步实验表明,在 CR 小鼠粘膜中观察到的基因表达极化与微生物群及其代谢物无关。我们采用的整体跨学科方法使我们能够表征宿主和微生物群对 CR 反应的各个监管方面。
The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR.
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