Microbiome-Vagal-Brain signaling: impact on the reward system and food intake

微生物组-迷走神经-大脑信号传导：对奖励系统和食物摄入的影响

基本信息

批准号：
9321458
负责人：
Claire de La Serre
金额：
$ 23.85万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9321458
关键词：
Ablation Adverse effects Affect Afferent Neurons Animals Anxiety Appetite Stimulants Appetitive Behavior Bacteria Behavior Blood - brain barrier anatomy Body Weight decreased Brain Brain Stem Brain region Calories Capsaicin Cell Nucleus Chronic Communication Corpus striatum structure Cues Data Desire for food Development Dopamine Dorsal Drug Design Eating Energy Intake Etiology Exhibits Fatty acid glycerol esters Food Food Preferences Gastrointestinal tract structure Gene Expression Germ-Free High Fat Diet Hyperphagia Hypothalamic structure Inflammation Infusion procedures Intake Knowledge Link Mediating Microdialysis Motivation Mus Neurons Neuropeptides Nucleus Accumbens Obesity Palate Pathogenicity Pathway interactions Peripheral Phenotype Physiology Population Probiotics Prosencephalon Proteins Rattus Regulation Research Rewards Ribosomes Role Route Satiation Signal Transduction Specificity Stimulus System Techniques Testing Thinness Vagotomy Vagus nerve structure Weight Gain Work base feeding food addiction food consumption gastrointestinal gut microbiota hedonic innovation interest mesolimbic system microbiome microbiota neurochemistry neurodevelopment novel pleasure prebiotics preference prevent response tool

项目摘要

ABSTRACT There is substantial evidence linking the gastrointestinal (GI) microbiota and obesity. Germ free (GF) mice do not gain weight when fed a high fat (HF) diet. Microbiota composition rapidly changes in response to HF feeding and colonization of GF animals with an “obese” microbiota results in recapitulation of the donor phenotype. This data suggest that an unfavorable microbiota is sufficient to cause obesity, however the mechanisms and pathways remain unclear. Excessive energy intake is the main cause for obesity. Food intake is regulated by homeostatic and hedonic cues. Hedonic eating refers to consumption of food “for pleasure”, in the absence of or beyond energy needs and is linked to reward signaling in the forebrain. Food consumption, particularly HF food, leads to the release of dopamine in the brain, hyper- and hyposensitivity of this system have been linked to abnormal weight gain. The microbiota has previously been shown to alter neural development and gene expression in the brain. However the potential influence of the microbiota on reward signaling and appetitive eating has yet to be studied. Using GF animals colonized with microbiota from lean or obese donors we will test the hypothesis that the microbiota reduces dopamine release in the nucleus accumbens to increase motivation and preference for fat. In order to aid in the development of microbiota- based therapies, it is necessary to understand the route by which the microbiota communicates to the brain. There is evidence that microbiota to brain signaling is relayed by vagal afferents innervating the GI tract but our understanding of the pathway is limited, partially because traditional techniques, such as vagotomy and capsaicin, lack specificity and can indirectly alter microbiota composition. In the second aim of this proposal, we will use a ribosome inactivating protein to ablate vagal afferent signaling in colonized animals. We aim to demonstrate that microbiota to brain communication is vagally mediated. Knowledge from this proposal will support the development of microbiota-based therapies aimed at food addiction and weight loss. Microbiota and vagal signaling could be more easily manipulated with fewer side effects than central targets.

抽象的有大量证据表明胃肠道 (GI) 微生物群与无菌 (GF) 之间存在联系。当喂食高脂肪（HF）饮食时，小鼠的体重不会因微生物群组成的快速变化而增加。 HF 喂养和具有“肥胖”微生物群的 GF 动物的定殖会导致供体的重现该数据表明不利的微生物群足以导致肥胖，但是能量摄入过多是导致肥胖的主要原因尚不清楚。受稳态和享乐暗示的调节，享乐饮食是指“为了快乐”而消费食物。缺乏或超出能量需求，并与前脑食物消耗的奖励信号有关，特别是高频食物，会导致大脑中多巴胺的释放，使该系统变得敏感或低敏感先前已证明微生物群与体重异常增加有关。然而，微生物群对奖励的潜在影响。信号传导和食欲饮食尚未使用定植有瘦肉或瘦肉的微生物群的 GF 动物进行研究。对于肥胖的捐赠者，我们将测试微生物群减少细胞核中多巴胺释放的假设伏隔核可以增加对脂肪的动力和偏好，以帮助微生物群的发展。基于治疗，有必要了解微生物群与大脑沟通的途径。有证据表明微生物群到大脑的信号传导是通过支配胃肠道的迷走神经传入来传递的，但我们的对这一途径的了解有限，部分原因是传统技术，如迷走神经切断术和辣椒素缺乏特异性，可以间接改变微生物群的组成。在该提案的第二个目标中，我们将使用核糖体失活蛋白来消除定植动物的迷走神经传入信号。证明微生物群与大脑的交流是通过迷走神经介导的。支持开发针对食物成瘾和减肥的基于微生物群的疗法。与中枢目标相比，迷走神经信号更容易操纵，副作用更少。