Bacteria sensory transduction from gut to brain to modulate behavior

摘要 肠道微生物与行为障碍有关，包括与食物摄入量和食欲有关的行为障碍。 肥胖和过度吞噬可以通过微生物从供体转移到无菌的受体小鼠身上。 移植。然而，在老鼠身上看到的相关效应还没有转化到临床上。有一个 迫切需要确定微生物信号如何改变宿主行为。具体地说，尚不清楚 胃肠道中产生的微生物刺激被转化为神经信号，加强行为。我们的这一差距 知识是一个重要的问题，因为了解微生物配体和胃肠道感觉功能是如何相互作用的 将允许合理设计基于肠道的疗法来治疗食物摄取障碍和促进情绪 幸福。 我们的实验室最近在一个突触中发现了连接肠腔和脑干的神经回路。 在神经足细胞和迷走神经细胞之间形成的这种神经回路将腔刺激传递到大脑。 毫秒(Kaelberer等人，2018年)。此外，在营养丰富的近端小肠中， 这种神经回路对于动物区分糖和甜味剂是必要的(Buchanan等人，2020)。在……上面 在此基础上，我们的假设是结肠神经足细胞与迷走神经突触传递奖赏 来自细菌的刺激。这项提议的目标是确定结肠神经足细胞是否感觉到细菌 配体，将细菌信号传递到迷走神经细胞，并调节奖励行为。 我们的理论基础是，通过阐明细菌从肠道到大脑、肠道的感觉传导机制 可以开发微生物疗法来治疗与饮食和肠道微生物有关的食物摄取障碍。

SUMMARY Gut microbes are associated with disorders of behavior, including those related to food intake and appetite. Obesity and hyperphagia can be transferred from donor to germ-free recipient mice, simply by microbial transplants. However, the correlative effects seen in mice have yet to be translated to the clinic. There is a critical need to determine how microbial signals alter host behaviors. Specifically, it is unknown how a microbial stimulus arising in the GI lumen is converted into a neural signal reinforces behavior. This gap in our knowledge is a significant problem because knowing how microbial ligands and GI sensory function interact will allow for rational design of gut-based therapies to treat disorders of food intake and promote emotional well-being. Our laboratory recently discovered a neural circuit linking the gut lumen with the brain stem in one synapse. Formed between neuropod cells and vagal neurons, this neural circuit transduces luminal stimuli to the brain in milliseconds (Kaelberer et al., 2018). Moreover, in the proximal small intestine where nutrients are abundant, this neural circuit is necessary for an animal to distinguish sugar from sweeteners (Buchanan et al., 2020). On this basis, our hypothesis is that colonic neuropod cells synapse with vagal neurons to communicate reward from bacterial stimuli. The objectives for this proposal are to define if colonic neuropod cells sense bacterial ligands, transduce bacterial signals onto vagal neurons, and modulate reward behavior. Our rationale is that by elucidating the mechanisms of bacterial sensory transduction from gut to brain, gut microbial therapeutics could be developed to treat disorders of food intake linked to diet and gut microbes.