A gut sensor for sugar preference

Abstract

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.

Publication
bioRxiv
Atharva Sahasrabudhe
Atharva Sahasrabudhe
Graduate Student

Graduate student

Seongjun Park
Assistant Professor at KAIST
Polina Anikeeva
Polina Anikeeva
Associate Professor in Materials Science and Engineering
Associate Professor in Brain and Cognitive Sciences
Associate Director, Research Laboratory of Electronics

My goal is to combine the current knowledge of biology and nanoelectronics to develop materials and devices for minimally invasive treatments for neurological and neuromuscular diseases.