TY - JOUR T1 - A gut sensor for sugar preference JF - bioRxiv DO - 10.1101/2020.03.06.981365 SP - 2020.03.06.981365 AU - Kelly L. Buchanan AU - Laura E. Rupprecht AU - Atharva Sahasrabudhe AU - M. Maya Kaelberer AU - Marguerita Klein AU - Jorge Villalobos AU - Winston W. Liu AU - Annabelle Yang AU - Justin Gelman AU - Seongjun Park AU - Polina Anikeeva AU - Diego V. Bohórquez Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/08/2020.03.06.981365.abstract N2 - Animals innately prefer caloric sugars over non-caloric sweeteners. Such preference depends on the sugar entering the intestine.1–4 Although the brain is aware of the stimulus within seconds,5–8 how the gut discerns the caloric sugar to guide choice is unknown. Recently, we discovered an intestinal transducer, known as the neuropod cell.9,10 This cell synapses with the vagus to inform the brain about glucose in the gut in milliseconds.10 Here, we demonstrate that neuropod cells distinguish a caloric sugar from a non-caloric sweetener using the electrogenic sodium glucose co-transporter 1 (SGLT1) or sweet taste receptors. Activation of neuropod cells by non-caloric sucralose leads to ATP release, whereas the entry of caloric sucrose via SGLT1 stimulates glutamate release. To interrogate the contribution of the neuropod cell to sugar preference, we developed a method to record animal preferences in real time while using optogenetics to silence or excite neuropod cells. We discovered that silencing these cells, or blocking their glutamatergic signaling, renders the animals unable to recognize the caloric sugar. And, exciting neuropod cells leads the animal to consume the non-caloric sweetener as if it were caloric. By transducing the precise identity of the stimuli entering the gut, neuropod cells guide an animal’s internal preference toward the caloric sugar. ER -