As the world's sixth mass extinction continues, the loss of large animals has widespread effects on biodiversity and ecosystem processes. Research across disparate systems, such as grasslands, marshes, forests, and coral reefs, shows that the effects of defaunation manifest even at the microbial scale, affecting microbial communities, microbe-driven processes, and host–microbe interactions. Microbiomes of foundation species, such as corals, trees, and grasses, appear especially vulnerable to the loss of large consumers, often resulting in disease, mortality, and regime shifts in ecosystems. We use the concepts of cascading consumer–prey interactions, as well as the bottom-up roles of consumers in ecosystems, to outline how future research can fill gaps in the field. For example, consumer diversity and body size affect the strength of trophic cascades and likely shape how defaunation affects microbiomes. Ultimately, we argue that the connections between macrobes and microbes are likely common but underappreciated, as the impacts of losing large consumers radiate throughout ecosystems.

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