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

Eukaryotic organisms are associated with complex microbial communities. Changes within these communities have been implicated in disease development. Nonetheless, it remains unclear whether these changes are a cause or a consequence of disease. Here, we report a causal link between environment-induced shifts in the microbiota and disease development. Using the model organism Hydra, we observed changes in microbial composition when transferring laboratory-grown Hydra to natural lake environments. These shifts were caused not only by new colonizers, through the process of community coalescence (merging of previously separate microbial communities), but also by lake water nutrients. Moreover, selective manipulation of the nutrient environment induced compound-specific shifts in the microbiota followed by disease development. Finally, L-arginine supplementation alone caused a transition in Pseudomonas from symbiotic to pathogenic, leading to an upregulation of immune response genes, tissue degradation, and host death. These findings challenge the notion that the host-associated microbiota is exclusively controlled by the host, highlighting the dynamic interplay between host epithelial environment, microbial colonizer pool, and nutrient conditions of the surrounding water. Furthermore, our results show that overfeeding of the microbiota allows for uncontrolled microbial growth and versatile interactions with the host. Environmental conditions may thus render symbionts a potential hazard to their hosts, blurring the divide between pathogenic and non-pathogenic microbes.IMPORTANCEThis study highlights the critical need to understand the dynamic interplay between host-associated microbiota and environmental factors to obtain a holistic view on organismal health. Our results demonstrate that ecosystem-wide microbial trafficking (community coalescence) and environmental nutrient conditions reshape microbial communities with profound implications for host health. By exploring nutrient-driven changes in microbial composition, our research finds experimental support for the "overfeeding hypothesis," which states that overfeeding alters the functionality of the host microbiota such that an overabundance in nutrients can facilitate disease development, transforming non-pathogenic microbes into pathogens. These findings emphasize the critical role of metabolic interactions driving microbial pathogenicity. Furthermore, our research provides empirical evidence for the "pathogenic potential" concept, challenging traditional distinctions between pathogenic and non-pathogenic microbes and supporting the idea that any microbe can become pathogenic under certain conditions.