Panorganismal Gut Microbiome-Host Metabolic Crosstalk
Panorganismal Gut Microbiome-Host Metabolic Crosstalk
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DOI：
10.1021/pr801068x
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Nicholson, Jeremy K.
中科院分区：
文献类型：
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作者：
Martin, Francois-Pierre J.;Sprenger, Norbert;Nicholson, Jeremy K.
协同进化塑造了生物体间的串扰，导致了人类疾病中肠道生态失调中观察到的深刻而多样的细胞和代谢变化。在这里，我们使用益生菌，益生菌和合生元调节简化的肠道微生物群，以评估小鼠全身代谢交换的深度，使用多室建模方法，其中代谢特征来自10个组织/液体隔室。营养诱导的微生物变化调制宿主的脂质，碳水化合物和氨基酸代谢在一个panorganismal规模。低聚半乳糖可降低肝脏和肾脏中的脂肪生成、三酰甘油与脂蛋白的结合以及甘油三酯浓度。这些变化与L.补充鼠李糖。在前合生素和合生素微生物调节后，在肝脏和胰腺中观察到转甲基化代谢途径（同型半胱氨酸-甜菜碱）的额外改变，这可能对控制葡萄糖代谢和胰岛素敏感性感兴趣。益生菌还减少了肝糖原和谷氨酰胺和肾上腺抗坏血酸，推断其对能量稳态、抗氧化和类固醇生成的影响。这些研究显示了肠道微生物组调节宿主生物化学的广度和深度，并揭示了主要哺乳动物代谢过程处于共生体内平衡控制之下。
Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.