Nutrition induced changes in the microbiota can cause dysbiosis and disease development

The increasing global prevalence of inflammatory and autoimmune diseases highlights the need to understand their origins. The overfeeding hypothesis suggests that disturbances in the microbiota due to diet may initiate these diseases. Using the model organism Hydra, we established a causal link between environmental alterations in the microbiota and disease development. Relocating Hydra to natural lakes caused significant microbial shifts due to new colonizers and nutrients. Nutrient manipulation removed the competitive advantage of the well-adapted resident microbiota, disrupted its nutrient-blocking capacity and triggered specific microbiota changes leading to disease. L-arginine supplementation alone transformed Pseudomonas from a commensal microbe into a pathogen, showing pathogenicity as context-dependent. Our findings support the overfeeding hypothesis, highlighting the role of microbial and nutrient dynamics in disease development.