Srinivasan Shriya S, Alshareef Amro, Hwang Alexandria, Bryne Ceara, Kuosmann Johannes, Ishida Keiko, Jenkins Joshua, Liu Sabrina, Madani Wiam Abdalla Mohammed, Hayward Alison M, Fabian Niora, Traverso Giovanni
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv. 2023 Jul 19:2023.07.17.549257. doi: 10.1101/2023.07.17.549257.
Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.
有效的肥胖治疗方法要么需要侵入性手术或内镜干预，要么需要患者高度依从，这使得近42%患有肥胖症的美国成年人难以有效控制病情。胃机械感受器感知胃的扩张，并进行与体积相关的迷走神经信号传递，以启动胃期并影响饱腹感。在本研究中，我们开发了一种新的腔内刺激方式，专门激活这些胃牵张感受器，以引发与机械扩张相称的迷走神经传入反应。在此，我们开发了振动可摄入生物电子刺激器（VIBES）药丸——一种可摄入装置，它进行腔内振动刺激以激活机械感受器并刺激黏膜感受器，从而诱导血清素释放，并产生与进食状态相称的激素代谢反应。我们在猪身上对108餐进行了VIBES评估，与未治疗的对照组相比，VIBES持续导致食物摄入量减少（约40%，p<0.0001），并使体重增加率最小化（p<0.03）。机械感受器生物学的应用可能会改变我们帮助患有营养障碍患者的能力。
