Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity
Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity
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DOI：
10.1172/jci72517
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发表时间：
2014-08-01
影响因子：
15.9
通讯作者：
Davies, Sean S.
中科院分区：
文献类型：
--
作者：
Chen, Zhongyi;Guo, Lilu;Davies, Sean S.
代谢紊乱，包括肥胖、糖尿病和心血管疾病，在西方国家很普遍。肠道微生物群组成是个体对这些疾病发展的易感性的一个促成因素;因此，改变一个人的微生物群可能会改善疾病。一种潜在的微生物群改变策略是将表达治疗因子的修饰细菌并入肠道微生物群中。例如，N-酰基磷脂酰乙醇胺（NAPE）是N-酰基乙醇酰胺（NAE）家族脂质的前体，其响应于进食在小肠中合成并减少食物摄入和肥胖。在这里，我们证明了给予工程化的表达NAPE的E。大肠杆菌Nissle 1917细菌在饮用水中8周降低了喂食高脂肪饮食的小鼠的肥胖水平。与接受标准水或对照细菌的小鼠相比，接受修饰细菌的小鼠的食物摄入量、肥胖、胰岛素抵抗和脂肪肝显著降低。表达NAPE的细菌所赋予的保护作用在从饮用水中去除后持续至少4周。此外，向TallyHo小鼠（一种肥胖的多基因小鼠模型）施用表达NAPE的细菌抑制了体重增加。我们的研究结果表明，将适当修饰的细菌掺入肠道微生物群中有可能成为抑制代谢紊乱发展的有效策略。
Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person's microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders.