Title: Gut-brain circuits for fat preference and immunity

Speaker：Dr. Meng-Tong Li， Columbia University, Zuckerman Institute 

Time: Nov. 6 (Monday), 1:00-2:30 PM

Venue：3rd floor lobby, Lui Che Woo Building

Host：Prof. Donggen Luo

Abstract

The body-brain axis is emerging as a principal conductor of organismal physiology.  It senses and controls organ function, metabolism and nutritional state.  

Previously we revealed a gut-to-brain, post-ingestive intestinal sugar-sensing pathway driving craving and attraction to sugar. Here, focusing on fat preference. We show that fat stimuli can induce behavioral attraction even without a functional taste system via the gut–brain axis to drive preference for fat. Using single-cell data, we identified the vagal neurons responding to intestinal delivery of fat, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference. Finally, we identified the receptors validated their role as the mediators of gut-to-brain fat-evoked responses.

Beyond nutrient preferences, the body-brain axis also plays a vital role in orchestrating immune responses.  We discovered a body-to-brain neural circuit informing the brain of an emerging inflammatory response.  Pro- and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to tell the brain of an emerging inflammatory response. Genetic silencing of this body-to-brain circuit produced unregulated and out-of-control inflammatory responses while activation of this circuit afforded exceptional neural control of immune responses. Using single-cell RNA sequencing and functional imaging, to identify the circuit components of this neuro-immune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state, offering possibilities for immune disorder modulation.

The intertwined discoveries related to both the gut-brain circuits involved in nutrient preferences, such as fat preference, and the body-brain circuit controlling immune responses highlight the complexity and integrative nature of the body-brain axis. Understanding and harnessing these connections offer promising avenues for developing interventions that target multiple aspects of physiological health, from metabolic well-being to immune system regulation.