Fructose liquid and solid formulations differently affect gut integrity, microbiota composition and related liver toxicity: a comparative in vivo study

Fructose liquid and solid formulations differently affect gut integrity, microbiota composition and related liver toxicity: a comparative in vivo study
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DOI:
10.1016/j.jnutbio.2018.02.003
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发表时间:
2018-05-01
影响因子:
5.6
通讯作者:
Collino, Massimo
Collino, Massimo
中科院分区:
医学2区
文献类型:
--
作者:
Mastrocola, Raffaella;Ferrocino, Ilario;Collino, Massimo

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尽管临床研究结果表明,虽然糖的浓度(液体与固体)可能显著影响代谢疾病的发展,但没有关于其制剂对肠道微生物群、完整性和肝脏结果的影响的实验数据。标准饮食加60%果糖糖浆(L-Fr)或60%果糖固体饮食加水(S-Fr),持续12周。肠道微生物群通过回肠内容物中微生物基因的16 S rRNA系统发育分析和鸟枪测序以及相关挥发物组分析来表征。果糖喂养导致肠道微生物群的改变,这取决于果糖配方,S-Fr组中梭菌属、颤螺旋菌属和梭菌目的定植增加,而拟杆菌属、乳杆菌属、L-Fr、S-Fr中的毛螺菌和Dorea引起回肠肠粘膜中晚期糖基化终末产物的最高积累和屏障损伤。这些作用与S-Fr小鼠肝脏中脂多糖依赖性促炎性TLR 4/NLRP 3炎性体途径的激活比L-Fr小鼠更强相关。相比之下,L-Fr摄入诱导更高水平的肝脂肪变性和纤维化标志物比S-Fr。果糖诱导的从头脂肪生成与SCFA和MCFA的生产通过宏基因组分析证实。这些结果表明,不同形式的果糖消费,液体或固体,可能会不同地影响肠道微生物群,从而导致肠粘膜完整性和肝脏稳态受损。(C)2018爱思唯尔公司All rights reserved.
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes.In the present sudy, C5781/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling.Fructose feeding led to alterations of the gut microbiota depending on the fructose formulation, with increased colonization by Clostridium, Oscillospira and Clostridiales phyla in the S-Fr group and Bacteroides, Lactobacillus, Lachnospiraceae and Dorea in the L-Fr. S-Fr evoked the highest accumulation of advanced glycation end products and barrier injury in the ileum intestinal mucosa. These effects were associated to a stronger activation of the lipopolysaccharide-dependent proinflammatory TLR4/NLRP3 inflammasome pathway in the liver of S-Fr mice than of L-Fr mice. In contrast, L-Fr intake induced higher levels of hepatosteatosis and markers of fibrosis than S-Fr. Fructose induced ex novo lipogenesis with production of SCFA and MCFA was confirmed by metagenomic analysis.These results suggest that consumption of fructose under different forms, liquid or solid, may differently affect gut microbiota, thus leading to impairment in intestinal mucosa integrity and liver homeostasis. (C) 2018 Elsevier Inc. All rights reserved.