Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates.
Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates.
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DOI：
10.3389/fmed.2021.646710
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发表时间：
2021
影响因子：
3.9
通讯作者：
Lusis AJ
中科院分区：
文献类型：
--
作者：
Lang JM;Sedgeman LR;Cai L;Layne JD;Wang Z;Pan C;Lee R;Temel RE;Lusis AJ
肠道微生物组影响营养加工以及宿主生理。血浆脂质水平与微生物组相关，尽管其潜在机制在很大程度上尚不清楚，并且膳食脂质对人类肠道微生物组的影响尚未得到充分研究。我们使用了四项利用非人类灵长类动物（绿猴和食蟹猴）的研究汇编，这些研究使用饮食和药理学技术操纵血浆脂质水平，并使用16 S rDNA表征微生物组。高脂肪饮食显着降低α多样性（香农）和厚壁菌门/拟杆菌的比例相比，普通饮食，即使当饮食有不同的组合物，并以不同的顺序应用。当使用DESeq 2分析差异丰度时，在两种食物饮食中，Bulleidia、梭菌属、瘤胃球菌属、真杆菌属、粪芽孢杆菌属、毛螺菌属、布劳特氏菌属、粪球菌属和颤螺菌属较大，而在两种高脂肪饮食（油酸混合物或猪油脂肪源）中，琥珀弧菌属、柯林斯菌属、链球菌属和乳球菌属较大。通过miR-33反义寡核苷酸（anti-miR-33）、尼曼-匹克C1样1（NPC 1 L1）反义寡核苷酸（阿索）和LDLR诱导降解剂（IDOL）阿索处理，饮食胆固醇水平不影响微生物组，也不影响血浆脂质水平的变化。然而，肝脏X受体（LXR）激动剂改变了微生物组并降低了胆汁酸水平。LXR激动剂增加了15个属，而7个属减少。假单胞菌增加LXR激动剂，并呈负相关，脱氧胆酸，胆酸，总胆汁酸，而瘤胃球菌与牛磺石胆酸和牛磺脱氧胆酸呈正相关。粪便中鉴定的9种胆汁酸中有7种由于LXR激动剂而显著降低，总胆汁酸（nmol/g）降低了62%。这些结果表明，血浆脂质水平至多对微生物组有适度的影响，而部分来源于血浆脂质的胆汁酸可能是脂质水平与微生物组之间间接关系的原因。
The gut microbiome influences nutrient processing as well as host physiology. Plasma lipid levels have been associated with the microbiome, although the underlying mechanisms are largely unknown, and the effects of dietary lipids on the gut microbiome in humans are not well-studied. We used a compilation of four studies utilizing non-human primates (Chlorocebus aethiops and Macaca fascicularis) with treatments that manipulated plasma lipid levels using dietary and pharmacological techniques, and characterized the microbiome using 16S rDNA. High-fat diets significantly reduced alpha diversity (Shannon) and the Firmicutes/Bacteroidetes ratio compared to chow diets, even when the diets had different compositions and were applied in different orders. When analyzed for differential abundance using DESeq2, Bulleidia, Clostridium, Ruminococcus, Eubacterium, Coprocacillus, Lachnospira, Blautia, Coprococcus, and Oscillospira were greater in both chow diets while Succinivibrio, Collinsella, Streptococcus, and Lactococcus were greater in both high-fat diets (oleic blend or lard fat source). Dietary cholesterol levels did not affect the microbiome and neither did alterations of plasma lipid levels through treatments of miR-33 antisense oligonucleotide (anti-miR-33), Niemann–Pick C1-Like 1 (NPC1L1) antisense oligonucleotide (ASO), and inducible degrader of LDLR (IDOL) ASO. However, a liver X receptor (LXR) agonist shifted the microbiome and decreased bile acid levels. Fifteen genera increased with the LXR agonist, while seven genera decreased. Pseudomonas increased on the LXR agonist and was negatively correlated to deoxycholic acid, cholic acid, and total bile acids while Ruminococcus was positively correlated with taurolithocholic acid and taurodeoxycholic acid. Seven of the nine bile acids identified in the feces significantly decreased due to the LXR agonist, and total bile acids (nmol/g) was reduced by 62%. These results indicate that plasma lipid levels have, at most, a modest effect on the microbiome, whereas bile acids, derived in part from plasma lipids, are likely responsible for the indirect relationship between lipid levels and the microbiome.