Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Mol Psychiatry. 2018 Dec;23(12):2287-2301. doi: 10.1038/s41380-018-0086-5. Epub 2018 Jun 18.
Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.
肥胖和糖尿病与人类焦虑和抑郁的发生率增加有关。为了了解肠道微生物组和大脑胰岛素抵抗在这些疾病中的作用，我们评估了饮食诱导肥胖（DIO）小鼠的行为和大脑胰岛素作用，以及有无抗生素治疗。我们发现，DIO 小鼠的行为表现出焦虑和抑郁增加。这与伏隔核和杏仁核中胰岛素信号的降低和炎症的增加有关。口服甲硝唑或万古霉素治疗可降低炎症，改善大脑中的胰岛素信号，并减少焦虑和抑郁的迹象。这些作用与色氨酸、GABA、BDNF、氨基酸和多种酰基辅酶 A 的水平变化有关，通过粪便移植可将这些作用转移到无菌小鼠中。因此，肠道微生物群的变化可以控制大脑胰岛素信号和代谢物水平，从而导致神经行为的改变。
