Using gnotobiotic ruminants to dissect host-microbe interactions for sustainable agriculture

Ruminant animals host one of the most complex gut microbial ecosystems, enabling the conversion of fibrous plant biomass into nutrient-dense foods such as meat and milk, which are essential for global food security. Over time, successive waves of research-from the initial recognition of microbes in the rumen, through anaerobic cultivation, to more recent multi-omics approaches-have progressively expanded our understanding of rumen microbial composition and its links to animal production and greenhouse gas emissions. Despite these advances, most insights into rumen microbial composition and traits of interest are based on associative or correlative evidence, and the host-derived mechanisms that actively shape rumen microbial composition and function remain poorly defined. Early gnotobiotic studies in ruminants demonstrated the value of maintaining animals under defined microbial conditions to dissect host-microbe interactions; however, this experimental capability has largely been lost from contemporary rumen research. This Perspective argues that revisiting gnotobiotic ruminant models is both timely and necessary for establishing causal mechanisms that govern host-microbe interactions in the rumen. Integrating gnotobiotic ruminant models is essential for establishing causal relationships between host biology and rumen microbial composition, thereby providing a foundation for biologically informed strategies that can enhance the sustainability of ruminant production systems.