Grant: Discovery Launch Supplement

Physical activity increases energy expenditure that contributes to energy balance; it may also improve the sensitivity of the appetite control system and thus help regulate food intake (FI). Homeostatic FI regulation involves a dynamic interaction between tonic (e.g., leptin, insulin) and episodic (e.g., ghrelin, GLP-1) signals, and a link between gut health and FI regulation has recently emerged. That is, bacterial byproducts in the gut (e.g., short chain fatty acids [SCFA]) functionally interact with and regulate appetite hormones (microbiota-gut-brain-axis [MGBA]). Research examining mechanisms by which habitual physical activity modulate the MGBA in the context of FI regulation in humans is poorly understood, particularly in aging when persons experience a change in satiety hormone production and a reduction in overall gut microbial diversity. Proposed mechanisms underlying habitual physical activity's effect on the MGBA include: (a) more sensitive tonic satiety signaling, (b) improved episodic satiety signaling, and (c) increased gut microbiota diversity and abundance of beneficial microbes (e.g., SCFA-producing bacteria). The long-term goals of this research program are the understand the regulation of the MGBA, including the impact of habitual physical activity, and identify potential genetic contributions. To achieve this goal, two short-term research objectives will be addressed: (1) examine the MGBA across a spectrum of physical activity levels in both middle-aged and older adults, equally distributed across sex; and (2) investigate association(s) between gut health and the responsiveness and sensitivity of FI hormones among those identified as high- and low-active persons in each age group. The above objectives will be met using a combination of advanced biochemistry and microbiology techniques and non-invasive experimental tests in humans. This program will incorporate cutting-edge analyses of gut microbiota composition and functional potential, novel indices of FI regulation (fasted, responsiveness, sensitivity), and novel approaches to assess `regulated' and `non-regulated' FI systems across the lifespan. This work will benefit multiple scientific domains by providing human data to inform the pathophysiology of energy imbalance. Students who participate in this research program will gain valuable experience in both applied human physiology and development of advanced bench science techniques, engaging in a flexible training environment to support academic-, medical-, and industry-track career paths. Emphasis will be placed on applied skills, and creative study design to target specific aspects of human FI regulation. Motivated by a clear long-term objective and student-focused training plan, this research program seeks to develop a new branch of metabolic physiology, generating foundational knowledge about how physical activity can modulate gut bacteria and implicate homeostatic FI regulation in the human body.