Feeding the microbiome in infection-induced anorexia

• Applicant: Professor Christoph Wilhelm, Ph.D.
• Subject Area: Immunology ; Nutritional Sciences
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560174243

Loss of appetite is an evolutionary conserved host adaptation known as sickness behaviour that evolved to survive disease. Infection-induced fasting responses are also commonly observed in diseases caused by pulmonary viruses. At the same time, our gut harbors countless metabolically active microbes that constantly adapt to the conditions imposed on them by their hosts. While normally at ease with their hosts, bacteria resort to the production of toxins and other virulence factors as a survival strategy to evade scarce nutrient availability and infiltrate new habitats. This bacterial stress response leads to a breach of the intestinal barrier, invasion of the host by the commensal microbiota and ultimately to pathogenesis. Therefore, fasting-induced nutrient deficiencies are likely to have a profound effect on the physiology of our intestinal ecosystem. Astonishingly little is known about if and how host metabolism adapts to the potential nutritional needs of stressed microbiota. Our recent observations suggest that to maintain their health, host organisms have evolved molecular responses to feed and pacify the stressed commensal microbiome during periods of limited nutrient supply. This project aims to explore the unappreciated interactions and trade-offs between host and microbial metabolism during pulmonary infections. We aim to uncover pivotal mechanisms through which commensal organisms communicate metabolic stress to the host and how these signals prompt changes in host metabolism to ensure nutrient supply to microbes. Defects in such microbiota-instructed compensatory host mechanisms could have dramatic consequences, as disruption in the intestinal barrier precedes a vast range of inflammatory conditions. Through this research, we aim to reconceptualize disease pathologies by focusing on microbial metabolism, with the goal of pinpointing targeted nutritional, antibiotic-independent strategies tailored to pacify bacteria when needed.

• DFG Programme: Reinhart Koselleck Projects
• Cooperation Partner: Professor Dr. Paul Wilmes