Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance.
Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance.
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肠道菌群调节饮食和遗传学之间的相互作用以影响葡萄糖耐受性。
DOI：
10.3390/medicines8070034
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发表时间：
2021-07-01
期刊：
影响因子：
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通讯作者：
Bridgewater LC
中科院分区：
文献类型：
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作者：
Franson JJ;Grose JH;Larson KW;Bridgewater LC
背景：代谢表型是多种因素之间复杂相互作用的结果，包括饮食，基因型和肠道微生物组。Per-Arnt-Sim（PAS）激酶是一种营养敏感的丝氨酸/苏氨酸激酶，其缺失（PASK−/−）可防止甘油三酯积累，胰岛素抵抗和高脂饮食中的体重增加;与肠道微生物组生态失调相关的条件。研究方法：在本文中，我们报告了饮食（高脂肪高糖，HFHS），基因型（PASK-/-）和微生物组（16 S测序）相互作用的代谢效应。结果如下：微生物组分析确定了饮食诱导的、基因型独立的分叉转变，HFHS小鼠的两个离散集群具有增加的β多样性和减少的α多样性。一个“较低”的簇包含厚壁菌门、拟杆菌门、放线菌门、变形菌门和双歧杆菌门的升高水平，并且与体重增加、葡萄糖耐受不良、甘油三酯积累和claudin-1表达降低相关。在集群内观察到基因型效应，较低集群的PASK−/−小鼠表现出体重增加和甘油三酯积累减少，而较高集群的PASK−/−对claudin-1减少具有抗性。结论：这些结果证实了之前的报道，即PAS激酶缺乏可以保护小鼠免受饮食的有害影响，并且它们表明微生物组失衡可以超越保护。此外，这些结果支持健康的饮食有利于微生物组的维持，并表明与代谢疾病相关的微生物罪魁祸首。
Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per–Arnt–Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK−/−) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK−/−), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A “lower” cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres, and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK−/− mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK−/− were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease.