Interplay between developmental shifts in gut physiology, the microbiome and juvenile growth

• Applicant: Dr. Gilles Storelli
• Subject Area: Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561529502

Animal development comprises several stages with specific goals, such as growth or reproduction. Each of these life stages has specific nutritional and metabolic needs, and certain organs must adjust their function to meet these demands. We study this interplay between development, organ physiology, and health with the invertebrate Drosophila. Drosophila have a rapid life cycle in which embryogenesis, infancy, puberty (metamorphosis) and adulthood are very distinct phases. Their juvenile phase is dedicated to growth and divided into three larval stages. We have discovered that a shift in intestinal function occurs during the last larval stage, with an acute activation of nutrient digestion, metabolism and transport. This switch accelerates systemic growth and maturation. We will now dissect the signaling networks that direct the functional maturation of the gut (Aim 1). Our findings also raise a paradox: given that nutrients are essential for growth, why is gut function not fully activated immediately after embryogenesis? This suggests that maximal gut function may be detrimental to the physiology of very young animals. We will determine if there are trade-offs between digestion, growth and health in juveniles. In particular, we will determine if high gut metabolism could facilitate microbiota dysbiosis (Aim 2). In parallel, digestive enzymes play a vital role in the breakdown of macronutrients, but cannot distinguish self from non-self and may damage tissues. We will determine if the production of digestive enzymes is delayed until the gut has acquired sufficient regenerative capacity (Aim 3). These studies will extend beyond our discovery that the physiology of the gut undergoes a radical change during development, and address two key features of this phenomenon: the mechanisms underlying this shift, and the physiological reasons for its timing. From a broader perspective, this work will determine if miscoordinations between intestinal function and development might affect juvenile health, and explore the contribution of the microbiome to these relationships.

• DFG Programme: Research Grants